NOVEL HETEROARYL-TRIAZOLE COMPOUNDS AS PESTICIDES

Abstract

The present invention relates to novel heteroaryl-triazole compounds of the general formula (I), in which the structural elements X, Y, R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4 and R.sup.5 have the meaning given in the description, to formulations and compositions comprising such compounds and for their use in the control of animal pests including arthropods and insects in plant protection and to their use for control of ectoparasites on animals.

##STR00001##

Claims

1. Compound of formula (I) ##STR00515## in which X is O or S; Y is a direct bond or optionally substituted CH.sub.2; R.sup.1 is hydrogen or hydroxy, or R.sup.1 is C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.2alkyl, phenyl-C.sub.1-C.sub.6alkyl, naphthyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkinyloxy, phenyl-C.sub.1-C.sub.6alkoxy or naphthyl-C.sub.1-C.sub.6alkoxy, wherein the C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.2alkyl, phenyl-C.sub.1-C.sub.6alkyl, naphthyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkinyloxy, phenyl-C.sub.1-C.sub.6alkoxy or naphthyl-C.sub.1-C.sub.6alkoxy is optionally substituted by one to five substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5, —SiMe.sub.3, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy-, C.sub.1-C.sub.6haloalkoxy-, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.1-C.sub.6alkylsulfonamido, —NHCO.sub.2—C.sub.1-C.sub.6alkyl, —OCONH—C.sub.1-C.sub.6alkyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkyl-amido, C.sub.3-C.sub.6cyclalkyl-amido, —CO.sub.2C.sub.1-C.sub.6alkyl, —CONH(C.sub.1-C.sub.6alkyl), —CONH(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CO—C.sub.3-C.sub.6cycloalkyl, —CON(C.sub.1-C.sub.6alkyl).sub.2, —C(═NOC.sub.1-C.sub.6alkyl)H, —C(═NOC.sub.1-C.sub.6alkyl)-C.sub.1-C.sub.6alkyl, and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, and C.sub.1-C.sub.6haloalkylsulfonyl, or R.sup.1 is heterocyclyl, heterocyclyl-C.sub.1-C.sub.6alkoxy or heterocyclyl-C.sub.1-C.sub.6alkyl, wherein the heterocyclyl is selected from the group consisting of saturated and partially unsaturated 4- to 10-membered heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl and the heterocyclyl, heterocyclyl-C.sub.1-C.sub.6alkoxy or heterocyclyl-C.sub.1-C.sub.6alkyl is optionally substituted by one to five substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5, —SiMe.sub.3, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy-, C.sub.1-C.sub.6haloalkoxy-, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.1-C.sub.6alkylsulfonamido, —NHCO.sub.2—C.sub.1-C.sub.6alkyl, —OCONH—C.sub.1-C.sub.6alkyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkyl-amido, C.sub.3-C.sub.6cyclalkyl-amido, —CO.sub.2C.sub.1-C.sub.6alkyl, —CONH(C.sub.1-C.sub.6alkyl), —CONH(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CO—C.sub.3-C.sub.6cycloalkyl, —CON(C.sub.1-C.sub.6alkyl).sub.2, —C(═NOC.sub.1-C.sub.6alkyl)H, —C(═NOC.sub.1-C.sub.6alkyl)-C.sub.1-C.sub.6alkyl, and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, and C.sub.1-C.sub.6haloalkylsulfonyl; R.sup.2 is phenyl, naphthyl, pyridine, pyrimidine, pyrazine or pyridazine each of which is optionally substituted with one to five substituents, each independently selected from the group consisting of halogen, hydroxy, —NH.sub.2, —CN, —SF.sub.5, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, —NO.sub.2, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.2-C.sub.6alkenylthio, C.sub.2-C.sub.6alkenylsulfinyl, C.sub.2-C.sub.6alkenylsulfonyl, C.sub.2-C.sub.6alkinylthio, C.sub.2-C.sub.6alkinylsulfinyl, C.sub.2-C.sub.6alkinylsulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, S—C.sub.1-C.sub.6alkylsulfinimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfinimidoyl, S—C.sub.2-C.sub.6alkenylsulfinimidoyl, S—C.sub.2-C.sub.6alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, S—C.sub.1-C.sub.6alkylsulfonimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfonimidoyl, S—C.sub.2-C.sub.6alkenylsulfonimidoyl, S—C.sub.2-C.sub.6alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.6alkyl, —NHCO-phenyl, —N(C.sub.1-C.sub.6alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —NHCO-heteroaryl, —N(C.sub.1-C.sub.6alkyl)CO-heteroaryl, —N(C.sub.3-C.sub.6cycloalkyl)CO-heteroaryl, —NHCO-heterocyclyl, —N(C.sub.1-C.sub.6alkyl)CO-heterocyclyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-heterocyclyl, —CO.sub.2C.sub.1-C.sub.6alkyl, —CONH(C.sub.1-C.sub.6alkyl), —CON(C.sub.1-C.sub.6alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH-phenyl, —CON(C.sub.1-C.sub.6alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —CONH-heteroaryl, —CON(C.sub.1-C.sub.6alkyl)heteroaryl, —CON(C.sub.3-C.sub.6cycloalkyl)heteroaryl, —CONH— heterocyclyl, —CON(C.sub.1-C.sub.6alkyl)heterocyclyl, —CON(C.sub.3-C.sub.6cycloalkyl)heterocyclyl, —C(═NOC.sub.1-C.sub.6alkyl)H, —C(═NOC.sub.1-C.sub.6alkyl)-C.sub.1-C.sub.6alkyl, —NHSO.sub.2—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —NHSO.sub.2-heterocyclyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-heterocyclyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-heterocyclyl, —NHSO.sub.2-heteroaryl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2-heteroaryl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-heteroaryl, —SO.sub.2NH(C.sub.1-C.sub.6alkyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —SO.sub.2NH(heteroaryl), —SO.sub.2N(C.sub.1-C.sub.6alkyl)(heteroaryl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(heteroaryl), —SO.sub.2NH(heterocyclyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(heterocyclyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(heterocyclyl), and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, and C.sub.1-C.sub.6haloalkylsulfonyl, and an optionally substituted 4- to 6-membered saturated or partially unsaturated heterocyclic ring, or R.sup.2 is heterocyclyl which is selected from the group consisting of saturated and partially unsaturated 4- to 10-membered heterocyclyl, 5-membered, 9-membered or 10-membered heteroaryl, each of which is optionally substituted by one to five substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.2-C.sub.6alkenylthio, C.sub.2-C.sub.6alkenylsulfinyl, C.sub.2-C.sub.6alkenylsulfonyl, C.sub.2-C.sub.6alkinylthio, C.sub.2-C.sub.6alkinylsulfinyl, C.sub.2-C.sub.6alkinylsulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, S—C.sub.1-C.sub.6alkylsulfinimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfinimidoyl, S—C.sub.2-C.sub.6alkenylsulfinimidoyl, S—C.sub.2-C.sub.6alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, S—C.sub.1-C.sub.6alkylsulfonimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfonimidoyl, S—C.sub.2-C.sub.6alkenylsulfonimidoyl, S—C.sub.2-C.sub.6alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.6alkyl, —NHCO-phenyl, —N(C.sub.1-C.sub.6alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —NHCO-heteroaryl, —N(C.sub.1-C.sub.6alkyl)CO-heteroaryl, —N(C.sub.3-C.sub.6cycloalkyl)CO-heteroaryl, —NHCO-heterocyclyl, —N(C.sub.1-C.sub.6alkyl)CO-heterocyclyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-heterocyclyl, —CO.sub.2C.sub.1-C.sub.6alkyl, —CONH(C.sub.1-C.sub.6alkyl), —CON(C.sub.1-C.sub.6alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH-phenyl, —CON(C.sub.1-C.sub.6alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —CONH-heteroaryl, —CON(C.sub.1-C.sub.6alkyl)heteroaryl, —CON(C.sub.3-C.sub.6cycloalkyl)heteroaryl, —CONH— heterocyclyl, —CON(C.sub.1-C.sub.6alkyl)heterocyclyl, —CON(C.sub.3-C.sub.6cycloalkyl)heterocyclyl, —C(═NOC.sub.1-C.sub.6alkyl)H, —C(═NOC.sub.1-C.sub.6alkyl)-C.sub.1-C.sub.6alkyl, —NHSO.sub.2—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —NHSO.sub.2-heterocyclyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-heterocyclyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-heterocyclyl, —NHSO.sub.2-heteroaryl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2-heteroaryl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-heteroaryl, —SO.sub.2NH(C.sub.1-C.sub.6alkyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —SO.sub.2NH(heteroaryl), —SO.sub.2N(C.sub.1-C.sub.6alkyl)(heteroaryl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(heteroaryl), —SO.sub.2NH(heterocyclyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(heterocyclyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(heterocyclyl), and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, and C.sub.1-C.sub.6haloalkylsulfonyl, and an optionally substituted 4- to 6-membered saturated or partially unsaturated heterocyclic ring, or R.sup.2 is in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl or C.sub.1-C.sub.6haloalkyl; R.sup.3a, R.sup.3b are independently selected from the group consisting of hydrogen, halogen and —CN, and C.sub.1-C.sub.6alkyl optionally substituted by one to three substituents independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2, in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, —CO.sub.2C.sub.1-C.sub.6alkyl, —CONH(C.sub.1-C.sub.6alkyl), and —CON(C.sub.1-C.sub.6alkyl).sub.2, and in each case optionally substituted C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, and benzyl wherein the phenyl substituent is optionally substituted with one to five substituents, each independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5 and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, and C.sub.1-C.sub.6alkylsulfonyl, and heterocyclyl-C.sub.1-C.sub.6alkyl wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered saturated and partially unsaturated heterocyclyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2 and in each case optionally substituted C.sub.1-C.sub.6alkyl, and C.sub.1-C.sub.6alkoxy, and phenyl optionally substituted with one to five substituents, each independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5 and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, and C.sub.1-C.sub.6alkylsulfonyl, and heterocyclyl wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered saturated and partially unsaturated heterocyclyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2 and in each case optionally substituted C.sub.1-C.sub.6alkyl, and C.sub.1-C.sub.6alkoxy, or R.sup.3a, R.sup.3b form together with the carbon to which they are connected a C.sub.3-C.sub.6-carbocyclic or 3- to 6-membered heterocyclic ring system, optionally substituted with one to two substituents, each independently selected from the group consisting of halogen, —CN, in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy and C.sub.1-C.sub.6haloalkoxy; R.sup.4 is pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl, wherein the pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl is optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CO.sub.2—C.sub.1-C.sub.6alkyl, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.2-C.sub.4alkenylsulfanyl, C.sub.2-C.sub.4alkenylsulfinyl, C.sub.2-C.sub.4alkenylsulfonyl, C.sub.2-C.sub.4alkinylsulfanyl, C.sub.2-C.sub.4alkinylsulfinyl, C.sub.2-C.sub.4alkinylsulfonyl, phenylsulfanyl, phenylsulfinyl, phenylsulfonyl, S—C.sub.1-C.sub.6alkylsulfinimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfinimidoyl, S—C.sub.2-C.sub.6alkenylsulfinimidoyl, S—C.sub.2-C.sub.6alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S—C.sub.1-C.sub.6alkylsulfonimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfonimidoyl, S—C.sub.2-C.sub.6alkenylsulfonimidoyl, S—C.sub.2-C.sub.6alkinylsulfonimidoyl, S-phenylsulfonimidoyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.6alkyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO-phenyl, —N(CO—C.sub.1-C.sub.6alkyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl).sub.2, —N(CO-phenyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO—C.sub.1-C.sub.6alkyl), —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO-phenyl), —N(CO—C.sub.1-C.sub.6alkyl)(CO-phenyl), —CONH(C.sub.1-C.sub.6alkyl), —CON(C.sub.1-C.sub.6alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH—SO.sub.2—C.sub.1-C.sub.6alkyl, —CONH—SO.sub.2-phenyl, —CONH—SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2—C.sub.1-C.sub.6alkyl, —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2-phenyl, —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CONH-phenyl, —CON(C.sub.1-C.sub.6alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —N(SO.sub.2C.sub.1-C.sub.6alkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.6haloalkyl).sub.2, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2—C.sub.1-C.sub.6haloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.1-C.sub.6alkyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —C(═NOC.sub.1-C.sub.6alkyl)H and —C(═NOC.sub.1-C.sub.6alkyl)-C.sub.1-C.sub.6alkyl, or R.sup.4 is a heterocyclic ring which is selected from the group consisting of 4- to 10-membered saturated or partially unsaturated heterocyclyl, 9-membered heteroaryl and 10-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2, and in each case optionally substituted —CO.sub.2—C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.2-C.sub.4alkenylsulfanyl, C.sub.2-C.sub.4alkenylsulfinyl, C.sub.2-C.sub.4alkenylsulfonyl, C.sub.2-C.sub.4alkinylsulfanyl, C.sub.2-C.sub.4alkinylsulfinyl, C.sub.2-C.sub.4alkinylsulfonyl, phenylsulfanyl, phenylsulfinyl, phenylsulfonyl, S—C.sub.1-C.sub.6alkylsulfinimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfinimidoyl, S—C.sub.2-C.sub.6alkenylsulfinimidoyl, S—C.sub.2-C.sub.6alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S—C.sub.1-C.sub.6alkylsulfonimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfonimidoyl, S—C.sub.2-C.sub.6alkenylsulfonimidoyl, S—C.sub.2-C.sub.6alkinylsulfonimidoyl, S-phenylsulfonimidoyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.6alkyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO-phenyl, —N(CO—C.sub.1-C.sub.6alkyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl).sub.2, —N(CO-phenyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO—C.sub.1-C.sub.6alkyl), —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO-phenyl), —N(CO—C.sub.1-C.sub.6alkyl)(CO-phenyl), —CONH(C.sub.1-C.sub.6alkyl), —CON(C.sub.1-C.sub.6alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH—SO.sub.2—C.sub.1-C.sub.6alkyl, —CONH—SO.sub.2-phenyl, —CONH—SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2—C.sub.1-C.sub.6alkyl, —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2-phenyl, —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CONH-phenyl, —CON(C.sub.1-C.sub.6alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —N(SO.sub.2C.sub.1-C.sub.6alkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.6haloalkyl).sub.2, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2—C.sub.1-C.sub.6haloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.1-C.sub.6alkyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —NHCS—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CS—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CS—C.sub.1-C.sub.6alkyl, —NHCS—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)CS—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CS—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CS-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CS-phenyl, —NHCS-phenyl, —CSNH(C.sub.1-C.sub.6alkyl), —CSN(C.sub.1-C.sub.6alkyl).sub.2, —CSNH(C.sub.3-C.sub.6cycloalkyl), —CSN(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —CSN(C.sub.3-C.sub.6cycloalkyl).sub.2, —CSNH-phenyl, —CSN(C.sub.1-C.sub.6alkyl)phenyl, —CSN(C.sub.3-C.sub.6cycloalkyl)phenyl, —C(═NOC.sub.1-C.sub.6alkyl)H, —C(═NOC.sub.1-C.sub.6alkyl)-C.sub.1-C.sub.6alkyl, phenyl and 5- to 6-membered heteroaryl, or R.sup.4 is pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl wherein the pyridine, pyrimidine, pyrazine or pyridazine is substituted with a total of one to three and the 5-membered heteroaryl with a total of one to two substituent(s), provided one substituent is selected from the following substructures S1-S39, in which the bond to the pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl is marked with a # and Z is CO, CS or SO.sub.2 and Y.sup.1 is independently selected from CO or SO.sub.2: ##STR00516## ##STR00517## ##STR00518##  and the other one or two optional substituent(s) are, each independently selected from the following group consisting of halogen, hydroxy, —CN, —COOH, —CO.sub.2—C.sub.1-C.sub.6alkyl, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2,  NH.sub.2, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.2-C.sub.4alkenylsulfanyl, C.sub.2-C.sub.4alkenylsulfinyl, C.sub.2-C.sub.4alkenylsulfonyl, C.sub.2-C.sub.4alkinylsulfanyl, C.sub.2-C.sub.4alkinylsulfinyl, C.sub.2-C.sub.4alkinylsulfonyl, phenylsulfanyl, phenylsulfinyl, phenylsulfonyl, S—C.sub.1-C.sub.6alkylsulfinimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfinimidoyl, S—C.sub.2-C.sub.6alkenylsulfinimidoyl, S—C.sub.2-C.sub.6alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S—C.sub.1-C.sub.6alkylsulfonimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfonimidoyl, S—C.sub.2-C.sub.6alkenylsulfonimidoyl, S—C.sub.2-C.sub.6alkinylsulfonimidoyl, S-phenylsulfonimidoyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.6alkyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO-phenyl, —N(CO—C.sub.1-C.sub.6alkyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl).sub.2, —N(CO-phenyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO—C.sub.1-C.sub.6alkyl), —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO-phenyl), —N(CO—C.sub.1-C.sub.6alkyl)(CO-phenyl), —CONH(C.sub.1-C.sub.6alkyl), —CON(C.sub.1-C.sub.6alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH—SO.sub.2—C.sub.1-C.sub.6alkyl, —CONH—SO.sub.2-phenyl, —CONH—SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2—C.sub.1-C.sub.6alkyl, —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2-phenyl, —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CONH-phenyl, —CON(C.sub.1-C.sub.6alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —N(SO.sub.2C.sub.1-C.sub.6alkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.6haloalkyl).sub.2, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2—C.sub.1-C.sub.6haloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.1-C.sub.6alkyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —C(═NOC.sub.1-C.sub.6alkyl)H and —C(═NOC.sub.1-C.sub.6alkyl)-C.sub.1-C.sub.6alkyl, R.sup.41 is a heterocyclic ring which is selected from the group consisting of 3- to 10-membered saturated or partially unsaturated heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2, and in each case optionally substituted —CO.sub.2—C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.2-C.sub.4alkenylsulfanyl, C.sub.2-C.sub.4alkenylsulfinyl, C.sub.2-C.sub.4alkenylsulfonyl, C.sub.2-C.sub.4alkinylsulfanyl, C.sub.2-C.sub.4alkinylsulfinyl, C.sub.2-C.sub.4alkinylsulfonyl, phenylsulfanyl, phenylsulfinyl, phenylsulfonyl, S—C.sub.1-C.sub.6alkylsulfinimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfinimidoyl, S—C.sub.2-C.sub.6alkenylsulfinimidoyl, S—C.sub.2-C.sub.6alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S—C.sub.1-C.sub.6alkylsulfonimidoyl, S—C.sub.3-C.sub.6cycloalkylsulfonimidoyl, S—C.sub.2-C.sub.6alkenylsulfonimidoyl, S—C.sub.2-C.sub.6alkinylsulfonimidoyl, S-phenylsulfonimidoyl, —NH(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl).sub.2, —NHCO—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CO—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.6alkyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO-phenyl, —N(CO—C.sub.1-C.sub.6alkyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl).sub.2, —N(CO-phenyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO—C.sub.1-C.sub.6alkyl), —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO-phenyl), —N(CO—C.sub.1-C.sub.6alkyl)(CO-phenyl), —CONH(C.sub.1-C.sub.6alkyl), —CON(C.sub.1-C.sub.6alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH—SO.sub.2—C.sub.1-C.sub.6alkyl, —CONH—SO.sub.2-phenyl, —CONH—SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2—C.sub.1-C.sub.6alkyl, —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2-phenyl, —CON(C.sub.1-C.sub.6alkyl)-SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CONH-phenyl, —CON(C.sub.1-C.sub.6alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —N(SO.sub.2C.sub.1-C.sub.6alkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.6haloalkyl).sub.2, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2—C.sub.1-C.sub.6haloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.6alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.1-C.sub.6alkyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.6alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —NHCS—C.sub.1-C.sub.6alkyl, —N(C.sub.1-C.sub.6alkyl)CS—C.sub.1-C.sub.6alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CS—C.sub.1-C.sub.6alkyl, —NHCS—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.6alkyl)CS—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CS—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CS-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CS-phenyl, —NHCS-phenyl, —CSNH(C.sub.1-C.sub.6alkyl), —CSN(C.sub.1-C.sub.6alkyl).sub.2, —CSNH(C.sub.3-C.sub.6cycloalkyl), —CSN(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —CSN(C.sub.3-C.sub.6cycloalkyl).sub.2, —CSNH-phenyl, —CSN(C.sub.1-C.sub.6alkyl)phenyl, —CSN(C.sub.3-C.sub.6cycloalkyl)phenyl, —C(═NOC.sub.1-C.sub.6alkyl)H, —C(═NOC.sub.1-C.sub.6alkyl)-C.sub.1-C.sub.6alkyl, phenyl and 5- to 6-membered heteroaryl, R.sup.42 is hydrogen, hydroxy, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, phenyl-C.sub.1-C.sub.6alkyl, naphthyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy-, C.sub.1-C.sub.6haloalkoxy, and phenyl, wherein the phenyl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, and C.sub.1-C.sub.6haloalkylsulfonyl, R.sup.43 is in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, phenyl-C.sub.1-C.sub.6alkyl, naphthyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy-, C.sub.1-C.sub.6haloalkoxy, and phenyl, wherein the phenyl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, and C.sub.1-C.sub.6haloalkylsulfonyl, R.sup.44 is in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, phenyl-C.sub.1-C.sub.6alkyl, naphthyl-C.sub.1-C.sub.6alkyl, R.sup.45 is hydrogen and in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, phenyl-C.sub.1-C.sub.6alkyl, naphthyl-C.sub.1-C.sub.6alkyl, or R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic optionally substituted 3- to 12-membered saturated or partially unsaturated heterocyclyl which may contain further heteroatoms; R.sup.5 is hydroxy, —C.sub.2-C.sub.6alkenyl, —C.sub.2-C.sub.6haloalkenyl, —C.sub.2-C.sub.6alkinyl, —C.sub.2-C.sub.6haloalkynyl, —CH.sub.2—SO.sub.2(C.sub.1-C.sub.6alkyl), —CH.sub.2—COO(C.sub.1-C.sub.6alkyl), —CF.sub.2—COO(C.sub.1-C.sub.6alkyl), —CH.sub.2—NH.sub.2, —CH.sub.2—NH—CO(C.sub.1-C.sub.6-alkoxy), —CH.sub.2—NH—CO—(C.sub.1-C.sub.6alkyl), —CH.sub.2—NH—CO—(C.sub.1-C.sub.6haloalkyl), —CH.sub.2—NH—CO—(C.sub.3-C.sub.6cycloalkyl), —CH.sub.2—NH—CO—(C.sub.3-C.sub.6halocycloalkyl), —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —CO—NH(C.sub.1-C.sub.6alkyl), —CO—NH(C.sub.1-C.sub.6haloalkyl), —CO—NH(C.sub.3-C.sub.6cycloalkyl), —CO—NH(C.sub.3-C.sub.6halocycloalkyl), —CO—NH(C.sub.2-C.sub.6alkenyl), —CO—NH(C.sub.2-C.sub.6haloalkenyl), —CO—NH(C.sub.2-C.sub.6alkinyl), —SO.sub.2NH.sub.2, —SO.sub.2NH(C.sub.1-C.sub.6alkyl), —SO.sub.2NH(C.sub.1-C.sub.6haloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6halocycloalkyl), —NH.sub.2, —NH(C.sub.1-C.sub.6alkyl), —NH(C.sub.1-C.sub.6alkoxy), —NH(C.sub.1-C.sub.6haloalkyl), —NH(C.sub.2-C.sub.6alkenyl), —NH(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6cycloalkyl), —NH(C.sub.1-C.sub.6alkyl)(C.sub.3-C.sub.6halocycloalkyl), —N(C.sub.1-C.sub.6alkyl)CO(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl)CO(C.sub.2-C.sub.6alkenyl), —N(C.sub.1-C.sub.6alkyl)CO(C.sub.1-C.sub.6alkoxy), —N(C.sub.1-C.sub.6alkyl)CO(C.sub.1-C.sub.6haloalkyl), —N(C.sub.1-C.sub.6alkyl)CO(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)CO(C.sub.3-C.sub.6halocycloalkyl), —NHCO(C.sub.1-C.sub.6alkyl), —NHCO(C.sub.2-C.sub.6alkenyl), —NHCO(C.sub.1-C.sub.6alkoxy), —NHCO(C.sub.1-C.sub.6haloalkyl), —NHCO(C.sub.3-C.sub.6cycloalkyl), —NHCO(C.sub.3-C.sub.6halocycloalkyl), —NHSO.sub.2(C.sub.1-C.sub.6alkyl), —NHSO.sub.2(C.sub.1-C.sub.6haloalkyl), —NHSO.sub.2(C.sub.3-C.sub.6cycloalkyl), —NHSO.sub.2(C.sub.3-C.sub.6halocycloalkyl), —N[SO.sub.2(C.sub.3-C.sub.6cycloalkyl)].sub.2, —N[SO.sub.2(C.sub.3-C.sub.6halocycloalkyl)].sub.2, —N(C.sub.1-C.sub.6alkyl)SO.sub.2(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl)SO.sub.2(C.sub.1-C.sub.6haloalkyl), —N(C.sub.1-C.sub.6alkyl)SO.sub.2(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.6alkyl)SO.sub.2(C.sub.3-C.sub.6halocycloalkyl), —C.sub.1-C.sub.6alkylthio, —C.sub.1-C.sub.6alkylsulfinyl, —C.sub.1-C.sub.6alkylsulfonyl, —C.sub.1-C.sub.6haloalkylthio, —C.sub.1-C.sub.6haloalkylsulfinyl, —C.sub.1-C.sub.6haloalkylsulfonyl, —C.sub.3-C.sub.6cycloalkylsulfanyl, —C.sub.3-C.sub.6cycloalkylsulfinyl, —C.sub.3-C.sub.6cycloalkylsulfonyl, —C.sub.2-C.sub.6alkenylsulfanyl, —C.sub.2-C.sub.6alkenylsulfinyl, C.sub.2-C.sub.6alkenylsulfonyl, —C.sub.2-C.sub.6alkinylsulfanyl, —C.sub.2-C.sub.6alkinylsulfinyl, C.sub.2-C.sub.6alkinylsulfonyl, —S—C.sub.1-C.sub.6alkylsulfinimidoyl, —S—C.sub.3-C.sub.6cycloalkylsulfinimidoyl, —S—C.sub.2-C.sub.6alkenylsulfinimidoyl, —S—C.sub.2-C.sub.6alkinylsulfinimidoyl, —S-phenylsulfinimidoyl, —S—C.sub.1-C.sub.6alkylsulfonimidoyl, —S—C.sub.3-C.sub.6cycloalkylsulfonimidoyl, —S—C.sub.2-C.sub.6alkenylsulfonimidoyl, —S—C.sub.2-C.sub.6alkinylsulfonimidoyl, wherein in each case a C.sub.1-C.sub.6alkyl group may be optionally substituted with a substituent independently selected from the group consisting of —CN, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, and C.sub.1-C.sub.4alkylsulfonyl, and in each case a C.sub.3-C.sub.6cycloalkyl group may be optionally substituted with a substituent independently selected from the group consisting of —CN, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkoxy, or R.sup.5 is phenyl, benzyl, phenethyl, pyridine, pyrimidine, pyrazine, pyridazine, furane, thiophene, imidazole, pyrazole, triazole, tetrazole, isoxazole, isothiazole, oxazole, thiazole, thiadiazole, oxadiazole, optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2 and the following substituents each of which optionally further substituted: C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl, C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.2-C.sub.6alkenylthio, C.sub.2-C.sub.6alkenylsulfinyl, C.sub.2-C.sub.6alkenylsulfonyl, C.sub.2-C.sub.6alkinylthio, C.sub.2-C.sub.6alkinylsulfinyl, C.sub.2-C.sub.6alkinylsulfonyl, —NH(C.sub.1-C.sub.6alkyl), —NH(C.sub.1-C.sub.6haloalkyl), —NH—CO(C.sub.1-C.sub.6alkyl), —NH—CO(C.sub.1-C.sub.6haloalkyl), —NH—CO(C.sub.3-C.sub.6cycloalkyl), —NH—CO(C.sub.3-C.sub.6halocycloalkyl), —NH—CO(C.sub.2-C.sub.6alkenyl), —NH—CO(C.sub.2-C.sub.6haloalkenyl), —NH—CO(C.sub.2-C.sub.6alkinyl), or R.sup.5 represents a group consisting of T1 in which the bond to the central triazole is marked with a # ##STR00519## wherein R.sup.51 is selected from C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, phenyl-C.sub.1-C.sub.6alkyl, and R.sup.52 is selected from C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, phenyl-C.sub.1-C.sub.6alkyl, wherein in each case a C.sub.1-C.sub.6alkyl group may be optionally substituted with a substituent independently selected from the group consisting of —CN, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, and C.sub.1-C.sub.4alkylsulfonyl, and in each case a C.sub.3-C.sub.6cycloalkyl group may be optionally substituted with a substituent independently selected from the group consisting of halogen, —CN, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkoxy, and a phenyl group may be optionally substituted with a substituent independently selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl and C.sub.1-C.sub.6haloalkylsulfonyl, or R.sup.51 and R.sup.52 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic optionally substituted 3- to 12-membered saturated or partially unsaturated heterocyclyl which may contain further heteroatoms.

2. Compound according to claim 1, in which X is O or S; Y is a direct bond or CH.sub.2; R.sup.1 is hydrogen or hydroxy, or R.sup.1 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.2alkyl, phenyl-C.sub.1-C.sub.4alkyl, naphthyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkinyloxy, phenyl-C.sub.1-C.sub.4alkoxy or naphthyl-C.sub.1-C.sub.4alkoxy wherein the C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.2alkyl, phenyl-C.sub.1-C.sub.4alkyl, naphthyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.3-C.sub.6alkenyloxy, C.sub.3-C.sub.6alkinyloxy, phenyl-C.sub.1-C.sub.4alkoxy or naphthyl-C.sub.1-C.sub.4alkoxy is optionally substituted by one to five substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5, —SiMe.sub.3, and in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy-, C.sub.1-C.sub.4haloalkoxy-, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.1-C.sub.4alkylsulfonamido, —NHCO.sub.2—C.sub.1-C.sub.4alkyl, —OCONH—C.sub.1-C.sub.4alkyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl-amido, C.sub.3-C.sub.6cycloalkyl-amido, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CONH(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6alkyl)CO—C.sub.3-C.sub.6cycloalkyl, —CON(C.sub.1-C.sub.4alkyl).sub.2, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl, or R.sup.1 is heterocyclyl, heterocyclyl-C.sub.1-C.sub.4alkoxy or heterocyclyl-C.sub.1-C.sub.4alkyl, wherein the heterocyclyl is selected from the group consisting of saturated and partially unsaturated 4- to 10-membered heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl and the heterocyclyl, heterocyclyl-C.sub.1-C.sub.4alkoxy or heterocyclyl-C.sub.1-C.sub.4alkyl is optionally substituted by one to five substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5, —SiMe.sub.3, and in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy-, C.sub.1-C.sub.4haloalkoxy-, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.1-C.sub.4alkylsulfonamido, —NHCO.sub.2—C.sub.1-C.sub.4alkyl, —OCONH—C.sub.1-C.sub.4alkyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl-amido, C.sub.3-C.sub.6cyclalkyl-amido, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CONH(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6alkyl)CO—C.sub.3-C.sub.6cycloalkyl, —CON(C.sub.1-C.sub.4alkyl).sub.2, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl; R.sup.2 is phenyl, naphthyl, pyridine, pyrimidine, pyrazine or pyridazine each of which is optionally substituted with one to three substituents, each independently selected from the group consisting of halogen, hydroxy, —NH.sub.2, —CN, —SF.sub.5, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, —NO.sub.2, and in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.2alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.2-C.sub.4alkenylthio, C.sub.2-C.sub.4alkenylsulfinyl, C.sub.2-C.sub.4alkenylsulfonyl, C.sub.2-C.sub.4alkinylthio, C.sub.2-C.sub.4alkinylsulfinyl, C.sub.2-C.sub.4alkinylsulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.4alkyl, —NHCO-phenyl, —N(C.sub.1-C.sub.4alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —NHCO-heteroaryl, —N(C.sub.1-C.sub.4alkyl)CO-heteroaryl, —N(C.sub.3-C.sub.6cycloalkyl)CO-heteroaryl, —NHCO-heterocyclyl, —N(C.sub.1-C.sub.4alkyl)CO-heterocyclyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-heterocyclyl, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH-phenyl, —CON(C.sub.1-C.sub.4alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —CONH-heteroaryl, —CON(C.sub.1-C.sub.4alkyl)heteroaryl, —CON(C.sub.3-C.sub.4cycloalkyl)heteroaryl, —CONH— heterocyclyl, —CON(C.sub.1-C.sub.4alkyl)heterocyclyl, —CON(C.sub.3-C.sub.6cycloalkyl)heterocyclyl, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, —NHSO.sub.2—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.4alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —NHSO.sub.2-heterocyclyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-heterocyclyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-heterocyclyl, —NHSO.sub.2-heteroaryl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-heteroaryl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-heteroaryl, —SO.sub.2NH(C.sub.1-C.sub.4alkyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —SO.sub.2NH(heteroaryl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(heteroaryl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(heteroaryl), —SO.sub.2NH(heterocyclyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(heterocyclyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(heterocyclyl), and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted with one to two substituents, each independently selected from the group consisting of halogen, —CN, in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy and C.sub.1-C.sub.4haloalkoxy, and an optionally substituted 4- to 6-membered saturated or partially unsaturated heterocyclic ring, or R.sup.2 is heterocyclyl which is selected from the group consisting of saturated and partially unsaturated 4- to 10-membered heterocyclyl, 5-membered, 9-membered or 10-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2; and in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.2alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.2-C.sub.4alkenylthio, C.sub.2-C.sub.4alkenylsulfinyl, C.sub.2-C.sub.4alkenylsulfonyl, C.sub.2-C.sub.4alkinylthio, C.sub.2-C.sub.4alkinylsulfinyl, C.sub.2-C.sub.4alkinylsulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.4alkyl, —NHCO-phenyl, —N(C.sub.1-C.sub.4alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —NHCO-heteroaryl, —N(C.sub.1-C.sub.4alkyl)CO-heteroaryl, —N(C.sub.3-C.sub.6cycloalkyl)CO-heteroaryl, —NHCO-heterocyclyl, —N(C.sub.1-C.sub.4alkyl)CO-heterocyclyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-heterocyclyl, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH-phenyl, —CON(C.sub.1-C.sub.4alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —CONH-heteroaryl, —CON(C.sub.1-C.sub.4alkyl)heteroaryl, —CON(C.sub.3-C.sub.4cycloalkyl)heteroaryl, —CONH— heterocyclyl, —CON(C.sub.1-C.sub.4alkyl)heterocyclyl, —CON(C.sub.3-C.sub.6cycloalkyl)heterocyclyl, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, —NHSO.sub.2—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.4alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —NHSO.sub.2-heterocyclyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-heterocyclyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-heterocyclyl, —NHSO.sub.2-heteroaryl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-heteroaryl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-heteroaryl, —SO.sub.2NH(C.sub.1-C.sub.4alkyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —SO.sub.2NH(heteroaryl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(heteroaryl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(heteroaryl), —SO.sub.2NH(heterocyclyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(heterocyclyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(heterocyclyl); and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted with one to two substituents, each independently selected from the group consisting of halogen, —CN, in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy and C.sub.1-C.sub.4haloalkoxy; and an optionally substituted 4- to 6-membered saturated or partially unsaturated heterocyclic ring, or R.sup.2 is C.sub.1-C.sub.4alkyl substituted with one substituent selected from the group consisting of C.sub.1-C.sub.3alkoxy-, C.sub.1-C.sub.3haloalkoxy-, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl, or C.sub.3-C.sub.6cycloalkyl optionally substituted with one or two substituents selected from the group consisting of halogen, —CN, —COOH, —CONH.sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), and —CON(C.sub.1-C.sub.4alkyl).sub.2; or C.sub.1-C.sub.4haloalkyl; R.sup.3a, R.sup.3b are independently selected from the group consisting of hydrogen, halogen, and —CN, and C.sub.1-C.sub.4alkyl optionally substituted by one to three substituents independently selected from the group consisting of hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl) and —CON(C.sub.1-C.sub.4alkyl).sub.2, and C.sub.3-C.sub.6cycloalkyl optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, —COOH, —CONH.sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl) and —CON(C.sub.1-C.sub.4alkyl).sub.2, and C.sub.1-C.sub.4haloalkyl optionally substituted with one to two substituents selected from the group consisting of hydroxy, —CN, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl) and —CON(C.sub.1-C.sub.4alkyl).sub.2, and C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl and C.sub.2-C.sub.6haloalkynyl, and benzyl wherein the phenyl substituent is optionally substituted with one to five substituents, each independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl, and heterocyclyl-C.sub.1-C.sub.4alkyl wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered saturated and partially unsaturated heterocyclyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.3haloalkyl and C.sub.1-C.sub.4alkoxy, and phenyl optionally substituted with one to five substituents, each independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl, and heterocyclyl wherein the heterocyclyl substituent is selected from the group consisting of 4- to 10-membered saturated and partially unsaturated heterocyclyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), hydroxy, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —NH.sub.2, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.3haloalkyl and C.sub.1-C.sub.4alkoxy, or R.sup.3a, R.sup.3b form together with the carbon to which they are connected a C.sub.3-C.sub.6-carbocyclic or 3- to 6-membered heterocyclic ring system, optionally substituted with one to two substituents, each independently selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy and C.sub.1-C.sub.3haloalkoxy; R.sup.4 is pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl, wherein the pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl is optionally substituted with one to three substituents selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CO.sub.2—C.sub.1-C.sub.6alkyl, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, wherein the alkyl is optionally substituted with —CN, C.sub.1-C.sub.6alkyl and C.sub.1-C.sub.4alkoxy; —NHCO—C.sub.1-C.sub.4haloalkyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, wherein the cycloalkyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl or C.sub.1-C.sub.4alkoxy; —NHCO-phenyl, wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy and C.sub.1-C.sub.4haloalkoxy; —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.3-C.sub.6cycloalkyl, wherein the cycloalkyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl or C.sub.1-C.sub.4alkoxy; —N(C.sub.1-C.sub.4alkyl)CO-phenyl, wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy and C.sub.1-C.sub.4haloalkoxy; —N(SO.sub.2C.sub.1-C.sub.3alkyl).sub.2, —NH(SO.sub.2C.sub.1-C.sub.3alkyl), —N(C.sub.1-C.sub.4alkyl)(SO.sub.2C.sub.1-C.sub.3alkyl), —N(SO.sub.2C.sub.1-C.sub.3haloalkyl).sub.2, —NH(SO.sub.2C.sub.1-C.sub.3haloalkyl), —CONH(C.sub.1-C.sub.4alkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —CONH—SO.sub.2—C.sub.1-C.sub.3alkyl, —CON(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —CONH(C.sub.1-C.sub.4haloalkyl), —CONH(C.sub.3-C.sub.6cycloalkyl), —CONH(C.sub.3-C.sub.6cyanocycloalkyl), —C(═NOC.sub.1-C.sub.4alkyl)H and —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl; and —CONH— phenyl, wherein the phenyl is optionally substituted with one to two substituents, each independently selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy and C.sub.1-C.sub.4haloalkoxy, or R.sup.4 is a heterocyclic ring which is selected from the group consisting of 4- to 10-membered saturated or partially unsaturated heterocyclyl, 9-membered heteroaryl and 10-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.6alkylthio, C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted with one to two substituents, each independently selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.3haloalkyl and C.sub.1-C.sub.4alkoxy, or R.sup.4 is pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl wherein the pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl is substituted with a total of one to three and the 5-membered heteroaryl with a total of one to two substituent(s), provided one substituent is selected from the following substructures S1-S39, in which the bond to the pyridine, pyrimidine, pyrazine, pyridazine or 5-membered heteroaryl is marked with a # and Z is CO, CS or SO.sub.2 and Y.sup.1 is independently selected from CO and SO.sub.2: ##STR00520## ##STR00521## ##STR00522## and the other one to two optional substituent(s) are each independently selected from the following group consisting of halogen, hydroxy, —ON, —COOH, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2; and —CO.sub.2—C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.4alkyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.4cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —CONH(C.sub.1-C.sub.4alkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —NHSO.sub.2—C.sub.1-C.sub.4alkyl, —NHSO.sub.2—C.sub.1-C.sub.4haloalkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.4alkyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.1-C.sub.4alkyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, R.sup.41 is a heterocyclic ring which is selected from the group consisting of 4- to 10-membered saturated or partially unsaturated heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl, each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2; and —CO.sub.2—C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.2-C.sub.4alkenylsulfanyl, C.sub.2-C.sub.4alkenylsulfinyl, C.sub.2-C.sub.4alkenylsulfonyl, C.sub.2-C.sub.4alkinylsulfanyl, C.sub.2-C.sub.4alkinylsulfinyl, C.sub.2-C.sub.4alkinylsulfonyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CO—C.sub.1-C.sub.4alkyl, —NHCO—C.sub.3-C.sub.4cycloalkyl, —N(C.sub.1-C.sub.4alkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CO—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.4alkyl)CO-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CO-phenyl, —NHCO-phenyl, —N(CO—C.sub.1-C.sub.4alkyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl).sub.2, —N(CO-phenyl).sub.2, —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO—C.sub.1-C.sub.4alkyl), —N(CO—C.sub.3-C.sub.6cycloalkyl)(CO-phenyl), —N(CO—C.sub.1-C.sub.4alkyl)(CO-phenyl), —CONH(C.sub.1-C.sub.4alkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.3-C.sub.6cycloalkyl).sub.2, —CONH—SO.sub.2—C.sub.1-C.sub.4alkyl, —CONH—SO.sub.2-phenyl, —CONH—SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.4alkyl)-SO.sub.2—C.sub.1-C.sub.4alkyl, —CON(C.sub.1-C.sub.4alkyl)-SO.sub.2-phenyl, —CON(C.sub.1-C.sub.4alkyl)-SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —CONH-phenyl, —CON(C.sub.1-C.sub.4alkyl)phenyl, —CON(C.sub.3-C.sub.6cycloalkyl)phenyl, —N(SO.sub.2C.sub.1-C.sub.4alkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.4haloalkyl).sub.2, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl).sub.2, —N(SO.sub.2C.sub.1-C.sub.4alkyl)SO.sub.2-phenyl, —N(SO.sub.2C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.1-C.sub.4alkyl, —NHSO.sub.2—C.sub.1-C.sub.4haloalkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—C.sub.1-C.sub.4alkyl, —NHSO.sub.2-phenyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2-phenyl, —NHSO.sub.2—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)SO.sub.2—(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.1-C.sub.4alkyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.6cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl).sub.2, —SO.sub.2NH(phenyl), —SO.sub.2N(C.sub.1-C.sub.4alkyl)(phenyl), —SO.sub.2N(C.sub.3-C.sub.6cycloalkyl)(phenyl), —NHCS—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CS—C.sub.1-C.sub.4alkyl, —N(C.sub.3-C.sub.6cycloalkyl)CS—C.sub.1-C.sub.4alkyl, —NHCS—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)CS—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.3-C.sub.6cycloalkyl)CS—(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.4alkyl)CS-phenyl, —N(C.sub.3-C.sub.6cycloalkyl)CS-phenyl, —NHCS-phenyl, —CSNH(C.sub.1-C.sub.4alkyl), —CSN(C.sub.1-C.sub.4alkyl).sub.2, —CSNH(C.sub.3-C.sub.6cycloalkyl), —CSN(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —CSN(C.sub.3-C.sub.6cycloalkyl).sub.2, —CSNH-phenyl, —CSN(C.sub.1-C.sub.4alkyl)phenyl, —CSN(C.sub.3-C.sub.6cycloalkyl)phenyl, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, phenyl and 5- to 6-membered heteroaryl, R.sup.42 is hydrogen, hydroxy, and C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, phenyl-C.sub.1-C.sub.4alkyl, naphthyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy-, C.sub.1-C.sub.4haloalkoxy, and phenyl, wherein the phenyl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, and C.sub.1-C.sub.4haloalkylsulfonyl, R.sup.43 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, phenyl-C.sub.1-C.sub.4alkyl, naphthyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy-, C.sub.1-C.sub.4haloalkoxy, and phenyl, wherein the phenyl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylthio, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, and C.sub.1-C.sub.4haloalkylsulfonyl, R.sup.44 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, phenyl-C.sub.1-C.sub.4alkyl, naphthyl-C.sub.1-C.sub.4alkyl, R.sup.45 is hydrogen and C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, phenyl-C.sub.1-C.sub.4alkyl, naphthyl-C.sub.1-C.sub.4alkyl, or R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached, represent a monocyclic, spirocyclic or bridged polycyclic 4- to 12-membered saturated or partially unsaturated heterocyclyl which may contain up to two further heteroatoms selected from the group of oxygen, nitrogen and sulfur and which is optionally substituted with one to three substituents selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —SF.sub.5, and —NH.sub.2; and in each case optionally substituted —CO.sub.2—C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, —NHSO.sub.2—C.sub.1-C.sub.4alkyl, —NHCO.sub.2—C.sub.1-C.sub.4alkyl, —OCONH—C.sub.1-C.sub.4alkyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.3-C.sub.6cycloalkyl, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —SO.sub.2NH(C.sub.1-C.sub.4alkyl); R.sup.5 is hydroxy, —C.sub.2-C.sub.4alkenyl, —C.sub.2-C.sub.4haloalkenyl, —C.sub.2-C.sub.4alkinyl, —CH.sub.2—SO.sub.2(C.sub.1-C.sub.4alkyl), —CH.sub.2—COO(C.sub.1-C.sub.4alkyl), —CH.sub.2—NH.sub.2, —CH.sub.2—NH—CO(C.sub.1-C.sub.4alkoxy), —CH.sub.2—NH—CO—(C.sub.1-C.sub.4alkyl), —CH.sub.2—NH—CO—(C.sub.1-C.sub.4haloalkyl), —CH.sub.2—NH—CO—(C.sub.1-C.sub.6cycloalkyl), —CH.sub.2—NH—CO—(C.sub.3-C.sub.6halocycloalkyl), —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —CO—NH(C.sub.1-C.sub.6alkyl), —CO—NH(C.sub.1-C.sub.4haloalkyl), —CO—NH(C.sub.3-C.sub.6cycloalkyl), —CO—NH(C.sub.2-C.sub.4alkenyl), —CO—NH(C.sub.2-C.sub.4haloalkenyl), —CO—NH(C.sub.2-C.sub.4alkinyl), —CO—NH(C.sub.3-C.sub.6halocycloalkyl), —NH.sub.2, —NH(C.sub.1-C.sub.4alkyl), —NH(C.sub.1-C.sub.4alkoxy), —NH(C.sub.1-C.sub.4haloalkyl), —NH(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —N(C.sub.1-C.sub.4alkyl)(C.sub.1-C.sub.4alkoxy), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.2-C.sub.4alkenyl), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.1-C.sub.4alkoxy), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.1-C.sub.4haloalkyl), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.3-C.sub.6cycloalkyl), N(C.sub.1-C.sub.4alkyl)CO(C.sub.3-C.sub.6halocycloalkyl), —NHCO(C.sub.1-C.sub.4alkyl), —NHCO(C.sub.2-C.sub.4alkenyl), —NHCO(C.sub.1-C.sub.4alkoxy), —NHCO(C.sub.1-C.sub.4haloalkyl), —NHCO(C.sub.3-C.sub.6cycloalkyl), —NHCO(C.sub.3-C.sub.6halocycloalkyl), —NHSO.sub.2(C.sub.1-C.sub.4alkyl), —NHSO.sub.2(C.sub.1-C.sub.4haloalkyl), —N[SO.sub.2(C.sub.3-C.sub.6cycloalkyl)].sub.2, —N[SO.sub.2(C.sub.3-C.sub.6halocycloalkyl)].sub.2, —NHSO.sub.2(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.4alkyl)SO.sub.2(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl)SO.sub.2(C.sub.1-C.sub.4haloalkyl), —N(C.sub.1-C.sub.4alkyl)SO.sub.2(C.sub.3-C.sub.6cycloalkyl), —C.sub.1-C.sub.4alkylthio, —C.sub.1-C.sub.4alkylsulfinyl, —C.sub.1-C.sub.4alkylsulfonyl, —C.sub.1-C.sub.4haloalkylthio, —C.sub.1-C.sub.4haloalkylsulfinyl, —C.sub.1-C.sub.4haloalkylsulfonyl, —C.sub.3-C.sub.6cycloalkylsulfanyl, —C.sub.3-C.sub.6cycloalkylsulfinyl, —C.sub.3-C.sub.6cyclo-alkylsulfonyl, —C.sub.2-C.sub.4alkenylsulfanyl, —C.sub.2-C.sub.4alkenylsulfinyl, C.sub.2-C.sub.4alkenyl-sulfonyl, —C.sub.2-C.sub.4alkinylsulfanyl, —C.sub.2-C.sub.4alkinylsulfinyl, C.sub.2-C.sub.4alkinylsulfonyl, or R.sup.5 is benzyl, pyridine, pyrimidine, pyrazine, pyridazine, furane, imidazole, pyrazole, triazole, tetrazole, isoxazole, isothiazole, oxazole, thiazole, thiadiazole, oxadiazole, optionally substituted with one to three substituents selected from the group consisting of halogen, —CN, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, NO.sub.2, —NH.sub.2 and the following substituents each of which optionally further substituted: C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, —NH(C.sub.1-C.sub.4alkyl), —NH(C.sub.1-C.sub.4haloalkyl), —NH—CO(C.sub.1-C.sub.4alkyl), —NH—CO(C.sub.1-C.sub.4haloalkyl), —NH—CO(C.sub.3-C.sub.6cycloalkyl), —NH—CO(C.sub.3-C.sub.6halocycloalkyl), —NH—CO(C.sub.2-C.sub.4alkenyl), —NH—CO(C.sub.2-C.sub.4haloalkenyl), or R.sup.5 represents a group consisting of T1 in which the bond to the central triazole is marked with a # ##STR00523## wherein R.sup.51 and R.sup.52 together with the nitrogen atom to which they are attached, represent a monocyclic, spirocyclic or bridged polycyclic 4- to 12-membered saturated or partially unsaturated heterocyclyl which may contain up to two further heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur and which is optionally substituted with one to three substituents selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CO.sub.2—C.sub.1-C.sub.4alkyl, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, and —NH.sub.2, and C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.3-C.sub.6cycloalkyl and C.sub.1-C.sub.4haloalkyl, wherein the C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkoxy, C.sub.3-C.sub.6cycloalkyl and C.sub.1-C.sub.4haloalkyl are optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, C.sub.1-C.sub.4alkyl, and C.sub.1-C.sub.4haloalkyl, and —NHSO.sub.2—C.sub.1-C.sub.4alkyl, —NHCO.sub.2—C.sub.1-C.sub.4alkyl, —OCONH—C.sub.1-C.sub.4alkyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —NHCO—C.sub.3-C.sub.6cycloalkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.3-C.sub.6cycloalkyl, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —SO.sub.2NH(C.sub.1-C.sub.4alkyl).

3. Compound according to claim 1, in which X is O or S; Y is a direct bond or CH.sub.2; R.sup.1 is hydrogen; or R.sup.1 is C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4alkynyl, C.sub.3-C.sub.4cycloalkyl, C.sub.3-C.sub.4cycloalkyl-C.sub.1-C.sub.2alkyl, phenyl-C.sub.1-C.sub.2alkyl or C.sub.1-C.sub.4alkoxy, wherein the C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, C.sub.2-C.sub.4haloalkynyl, C.sub.3-C.sub.4cycloalkyl, C.sub.3-C.sub.4cycloalkyl-C.sub.1-C.sub.2alkyl, phenyl-C.sub.1-C.sub.2alkyl or C.sub.1-C.sub.4alkoxy is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5, —SiMe.sub.3, and C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.4alkoxy-, C.sub.1-C.sub.4haloalkoxy-, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.4cycloalkylkylthio, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, —NHCO.sub.2—C.sub.1-C.sub.4alkyl, —OCONH—C.sub.1-C.sub.4alkyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CONH(C.sub.3-C.sub.4cycloalkyl), —N(C.sub.3-C.sub.4alkyl)CO—C.sub.3-C.sub.4cycloalkyl, —CON(C.sub.1-C.sub.4alkyl).sub.2, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, or in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.4cycloalkylthio, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl, or R.sup.1 is heterocyclyl or heterocyclyl-C.sub.1-C.sub.2alkyl, wherein the heterocyclyl is selected from the group consisting of saturated and partially unsaturated 4- to 10-membered heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl and the heterocyclyl or heterocyclyl-C.sub.1-C.sub.2alkyl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2, —SF.sub.5, —SiMe.sub.3, and C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.4alkoxy-, C.sub.1-C.sub.4haloalkoxy-, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.4cycloalkylkylthio, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl, —NHCO.sub.2—C.sub.1-C.sub.4alkyl, —OCONH—C.sub.1-C.sub.4alkyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CONH(C.sub.3-C.sub.4cycloalkyl), —N(C.sub.3-C.sub.4alkyl)CO—C.sub.3-C.sub.4cycloalkyl, —CON(C.sub.1-C.sub.4alkyl).sub.2, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, or in each case optionally substituted C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.4cycloalkylthio, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl; R.sup.2 is phenyl or pyridine, optionally substituted with one to three substituents, each independently selected from the group consisting of halogen, —CN, —SF.sub.5, —NO.sub.2; C.sub.1-C.sub.4alkyl, optionally substituted by —CN; C.sub.3-C.sub.4cycloalkyl, optionally substituted by halogen, —CN, C.sub.1-C.sub.3haloalkyl; C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.4cycloalkylthio, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heteroarylthio, heteroarylsulfinyl and heteroarylsulfonyl, or R.sup.2 is 5-membered heteroaryl, wherein the 5-membered heteroaryl is optionally substituted with one to three substituents, each independently selected from the group consisting of halogen, —CN, SF.sub.5, NO.sub.2; C.sub.1-C.sub.4alkyl, optionally substituted by —CN; C.sub.3-C.sub.4cycloalkyl, optionally substituted by halogen, —CN, C.sub.1-C.sub.3haloalkyl; C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.4cycloalkylthio, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heteroarylthio, heteroarylsulfinyl and heteroarylsulfonyl; R.sup.3a, R.sup.3b are independently selected from the group consisting of hydrogen; C.sub.1-C.sub.6alkyl optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, —NO.sub.2, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl; C.sub.3-C.sub.6cycloalkyl; C.sub.1-C.sub.6haloalkyl; R.sup.4 is pyridine, pyrimidine, pyrazine, pyridazine or thiazole, wherein (A) the pyridine, pyrimidine, pyrazine or pyridazine is optionally substituted with one to three substituents selected from the group consisting of halogen, —CN, —NH.sub.2, —NO.sub.2, —COOH, —CONH.sub.2, —CSNH.sub.2, —CO.sub.2—C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NHCO—C.sub.1-C.sub.3alkyl, —N(C.sub.1-C.sub.3alkyl)CO—C.sub.1-C.sub.3alkyl, —NHCO—C.sub.1-C.sub.3cyanoalkyl, —N(C.sub.1-C.sub.3alkyl)CO—C.sub.1-C.sub.3cyanoalkyl, —NHCO—C.sub.1-C.sub.3haloalkyl, —N(C.sub.1-C.sub.3alkyl)CO—C.sub.1-C.sub.3haloalkyl —NHCO—C.sub.3-C.sub.4cycloalkyl, wherein the cycloalkyl is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, —CN, C.sub.1-C.sub.6alkyl or C.sub.1-C.sub.4alkoxy; —N(C.sub.1-C.sub.3alkyl)CO—C.sub.3-C.sub.4cycloalkyl, wherein the cycloalkyl is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, —CN, C.sub.1-C.sub.6alkyl or C.sub.1-C.sub.4alkoxy; —NHCO-phenyl, wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy and C.sub.1-C.sub.3haloalkoxy; —NHSO.sub.2—C.sub.1-C.sub.3alkyl, —NHSO.sub.2—C.sub.1-C.sub.3haloalkyl, —CONH(C.sub.1-C.sub.3alkyl), —CON(C.sub.1-C.sub.3alkyl).sub.2, —CONH—SO.sub.2—C.sub.1-C.sub.3alkyl, CON(C.sub.1-C.sub.3alkyl)-SO.sub.2—C.sub.1-C.sub.3alkyl, —CONH(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.3alkyl)(C.sub.3-C.sub.6cycloalkyl), —CONH(C.sub.1-C.sub.3haloalkyl), —CON(C.sub.1-C.sub.3alkyl)(C.sub.1-C.sub.3haloalkyl), —CONH(C.sub.1-C.sub.3cyanoalkyl), —CON(C.sub.1-C.sub.3alkyl)(C.sub.1-C.sub.3cyanoalkyl), —CONH(1-cyano-C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.3alkyl)(1-cyano-C.sub.3-C.sub.6cycloalkyl), —CONH— phenyl, wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy and C.sub.1-C.sub.3haloalkoxy, and (B) the thiazole is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, —NO.sub.2, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl and C.sub.1-C.sub.3haloalkylsulfonyl, or R.sup.4 is pyridine, pyrimidine or thiazole, wherein the pyridine, pyrimidine or thiazole is substituted with a total of one to two substituent(s), provided one substituent is selected from the following substructures S1, S2, and S18 in which the bond to the pyridine, pyrimidine or thiazole is marked with a # and Z is CO: ##STR00524## the other optional substituent is selected the following group consisting of halogen, hydroxy, —CN, —COOH, —CO.sub.2—C.sub.1-C.sub.3alkyl, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —NH.sub.2; and C.sub.1-C.sub.3alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, C.sub.3-C.sub.4cycloalkylsulfanyl, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, R.sup.41 is a heterocyclic ring which is selected from the group consisting of 4- to 8-membered saturated or partially unsaturated heterocyclyl, 5-membered heteroaryl and 6-membered heteroaryl, each of which is optionally substituted by one to two substituents independently selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, —SF.sub.5, —NH.sub.2, and —CO.sub.2—C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.4cycloalkylsulfanyl, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NH(C.sub.1-C.sub.3alkyl), —N(C.sub.1-C.sub.3alkyl).sub.2, —NHCO—C.sub.1-C.sub.3alkyl, —N(C.sub.1-C.sub.3alkyl)CO—C.sub.1-C.sub.3alkyl, —N(C.sub.3-C.sub.4cycloalkyl)CO—C.sub.1-C.sub.3alkyl, —NHCO—C.sub.3-C.sub.4cycloalkyl, —N(C.sub.1-C.sub.3alkyl)CO—(C.sub.3-C.sub.4cycloalkyl), —N(C.sub.3-C.sub.4cycloalkyl)CO—(C.sub.3-C.sub.4cycloalkyl), —CONH(C.sub.1-C.sub.3alkyl), —CON(C.sub.1-C.sub.3alkyl).sub.2, —CONH(C.sub.3-C.sub.4cycloalkyl), —CON(C.sub.1-C.sub.3alkyl)(C.sub.3-C.sub.4cycloalkyl), —CON(C.sub.3-C.sub.4cycloalkyl).sub.2, —NHSO.sub.2—C.sub.1-C.sub.3alkyl, —NHSO.sub.2—C.sub.1-C.sub.3haloalkyl, —N(C.sub.1-C.sub.3alkyl)SO.sub.2—C.sub.1-C.sub.3alkyl, —N(C.sub.3-C.sub.4cycloalkyl)SO.sub.2—C.sub.1-C.sub.3alkyl, —NHSO.sub.2—C.sub.3-C.sub.4cycloalkyl, —N(C.sub.1-C.sub.3alkyl)SO.sub.2—(C.sub.3-C.sub.4cycloalkyl), —N(C.sub.3-C.sub.4cycloalkyl)SO.sub.2—(C.sub.3-C.sub.4cycloalkyl), —SO.sub.2NH(C.sub.1-C.sub.3alkyl), —SO.sub.2N(C.sub.1-C.sub.3alkyl).sub.2, —SO.sub.2N(C.sub.1-C.sub.3alkyl)(C.sub.3-C.sub.4cycloalkyl), —SO.sub.2NH(C.sub.3-C.sub.4cycloalkyl), —SO.sub.2N(C.sub.3-C.sub.4cycloalkyl).sub.2, R.sup.42 is hydrogen, hydroxy, and C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4alkynyl, C.sub.3-C.sub.4cycloalkyl, C.sub.3-C.sub.4cycloalkyl-C.sub.1-C.sub.2alkyl, phenyl-C.sub.1-C.sub.2alky, C.sub.1-C.sub.3alkoxy, R.sup.43 is C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4alkynyl, C.sub.3-C.sub.4cycloalkyl, C.sub.3-C.sub.4cycloalkyl-C.sub.1-C.sub.2alkyl, phenyl-C.sub.1-C.sub.2alkyl, C.sub.1-C.sub.3alkoxy, or R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached, represent a monocyclic, spirocyclic or bridged polycyclic 4- to 8-membered saturated heterocyclyl which may contain up to one further heteroatom selected from the group of oxygen, nitrogen and sulfur and which is optionally substituted with one to three substituents selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, and —CN; and —CO.sub.2—C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.4cycloalkylsulfanyl, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NHCO—C.sub.1-C.sub.3alkyl, —N(C.sub.1-C.sub.3alkyl)CO—C.sub.1-C.sub.3alkyl, —NHCO—C.sub.1-C.sub.3cycloalkyl, —N(C.sub.1-C.sub.3alkyl)CO—C.sub.3-C.sub.4cycloalkyl, —CO.sub.2C.sub.1-C.sub.3alkyl, —CONH(C.sub.1-C.sub.3alkyl), —CONH(C.sub.3-C.sub.4cycloalkyl), and —CON(C.sub.1-C.sub.3alkyl).sub.2; R.sup.5 is hydroxy, —C.sub.2-C.sub.4alkenyl, —C.sub.2-C.sub.4haloalkenyl, —C.sub.2-C.sub.4alkinyl, —CH.sub.2—SO.sub.2(C.sub.1-C.sub.3alkyl), —CH.sub.2—COO(C.sub.1-C.sub.4alkyl), —CH.sub.2—NH.sub.2, —CH.sub.2—NH—CO(C.sub.1-C.sub.4alkoxy), —CH.sub.2—NH—CO—(C.sub.1-C.sub.4alkyl), —CH.sub.2—NH—CO—(C.sub.1-C.sub.4haloalkyl), —CH.sub.2—NH—CO—(C.sub.3-C.sub.6cycloalkyl), —CN, —COOH, —CONH.sub.2, —CO—NH(C.sub.1-C.sub.4alkyl), —CO—NH(C.sub.1-C.sub.4haloalkyl), —CO—NH(C.sub.3-C.sub.6cycloalkyl), —CO—NH(C.sub.2-C.sub.4alkenyl), —CO—NH(C.sub.2-C.sub.4haloalkenyl), —CO—NH(C.sub.2-C.sub.4alkinyl), —CO—NH(C.sub.3-C.sub.6halocycloalkyl), —NH.sub.2, —NH(C.sub.1-C.sub.4alkyl), —NH(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —N(C.sub.1-C.sub.4alkyl)(C.sub.1-C.sub.4alkoxy), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.2-C.sub.4alkenyl), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.1-C.sub.4alkoxy), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.1-C.sub.6haloalkyl), —N(C.sub.1-C.sub.4alkyl)CO(C.sub.3-C.sub.6cycloalkyl), —NHCO(C.sub.1-C.sub.4alkyl), —NHCO(C.sub.2-C.sub.4alkenyl), —NHCO(C.sub.1-C.sub.4alkoxy), —NHCO(C.sub.1-C.sub.4haloalkyl), —NHCO(C.sub.3-C.sub.6cycloalkyl), —NHCO(C.sub.3-C.sub.6halocycloalkyl), —NHSO.sub.2(C.sub.1-C.sub.4alkyl), —NHSO.sub.2(C.sub.1-C.sub.4haloalkyl), —N[SO.sub.2(C.sub.3-C.sub.6cycloalkyl)].sub.2, —N[SO.sub.2(C.sub.3-C.sub.6halocycloalkyl)].sub.2, —NHSO.sub.2(C.sub.3-C.sub.6cycloalkyl), —N(C.sub.1-C.sub.4alkyl)SO.sub.2(C.sub.1-C.sub.6alkyl), —N(C.sub.1-C.sub.6alkyl)SO.sub.2(C.sub.1-C.sub.4haloalkyl), —N(C.sub.1-C.sub.4alkyl)SO.sub.2(C.sub.3-C.sub.6cycloalkyl), —C.sub.1-C.sub.4alkylthio, —C.sub.1-C.sub.4alkylsulfinyl, —C.sub.1-C.sub.4alkylsulfonyl, —C.sub.1-C.sub.4haloalkylthio, —C.sub.1-C.sub.4haloalkylsulfinyl, —C.sub.1-C.sub.4haloalkylsulfonyl, —C.sub.3-C.sub.4cycloalkylsulfanyl, —C.sub.3-C.sub.6cycloalkylsulfinyl, —C.sub.3-C.sub.6cyclo-alkylsulfonyl, or R.sup.5 represents a group consisting of T1 in which the bond to the central triazole is marked with a # ##STR00525## wherein R.sup.51 and R.sup.52 together with the nitrogen atom to which they are attached, represent monocyclic 5- to 6-membered saturated heterocyclyl selected from the group of pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl which is optionally substituted with one to three substituents selected from the group consisting of fluorine, chlorine, bromine, ═O (oxo), ═S (thiono), hydroxy, —CN, —COOH, —CO.sub.2—C.sub.1-C.sub.4alkyl, —SO.sub.2NH.sub.2, —CONH.sub.2, —CSNH.sub.2, —NO.sub.2, and —NH.sub.2; and C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3cyanoalkyl, C.sub.3-C.sub.6cycloalkyl, wherein C.sub.3-C.sub.6cycloalkyl is optionally substituted by one to three substituents independently selected from the group consisting of halogen, —CN, and C.sub.1-C.sub.4alkyl, or R.sup.5 is benzyl, pyridine, pyrimidine, pyrazine, pyridazine, furane, pyrazole, triazole, tetrazole, isoxazole, oxazole, oxadiazole, optionally substituted with one to three substituents selected from the group consisting of halogen, —CN, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, NO.sub.2, —NH.sub.2 and the following substituents each of which optionally further substituted: C.sub.1-C.sub.3alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NH—CO(C.sub.1-C.sub.3alkyl), —NH—CO(C.sub.1-C.sub.3haloalkyl), —NH—CO(C.sub.2-C.sub.4alkenyl), and —NH—CO(C.sub.2-C.sub.4haloalkenyl).

4. Compound according to claim 1, in which X is O; Y is a direct bond; R.sup.1 is hydrogen, 2-propen-1-yl, 3-methyl-but-2-en-1-yl, 3,3-difluoro-prop-2-en-1-yl, 3,3-dichloro-prop-2-en-1-yl, or 2-propyn-1-yl, or R.sup.1 is C.sub.1-C.sub.3alkyl optionally substituted with one substituent selected from the group consisting of hydroxy, halogen, —CN, methyl, ethyl, iso-propyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, iso-propyloxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, 2,2-difluoroethyl, and 2,2,2-trifluoroethyl, or R.sup.1 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, each of which optionally substituted with one or two substituents selected from the group consisting of fluorine, chlorine, —CN, methyl, ethyl, methoxy, ethoxy and trifluoromethyl, or R.sup.1 is cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropyl-1-ethyl, cyclobutyl-1-ethyl, each carbocyclus optionally substituted with one or two substituents selected from the group consisting of fluorine, chlorine, —CN, methyl, ethyl, methoxy, ethoxy, trifluoromethyl and phenyl, or R.sup.1 is benzyl, phenyl-1-ethyl, phenyl-2-ethyl, each carbocyclus optionally substituted with one to three substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, —CN, methyl, ethyl, iso-propyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, iso-propyloxy, n-propyloxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl and trifluoromethylsulfonyl, or R.sup.1 is heterocyclylmethyl, heterocyclyl-1-ethyl and heterocyclyl-2-ethyl wherein the heterocyclyl is selected from the group consisting of azetidinyl, oxetanyl, thietanyl, 1,1-dioxothietan-3-yl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, 1,4-dioxanyl, piperidinyl, piperazinyl, morpholinyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, thienyl, furyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrimidinyl, pyridazinyl and pyrazinyl, each heterocyclus optionally substituted with one to three substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, —CN, methyl, ethyl, iso-propyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, iso-propyloxy, n-propyloxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl and trifluoromethylsulfonyl; R.sup.2 is phenyl, optionally substituted with one to three substituents, each independently selected from the group consisting of fluorine, chlorine, bromine, iodine, —CN, —SF.sub.5, —NO.sub.2, methyl, 1-cyano-1-methylethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, cyclopropyl, 1-cyanocyclopropyl, 1-(trifluoromethyl)cyclopropyl, methoxy, difluoromethoxy, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, isopropylthio, isopropylsulfinyl, isopropylsulfonyl, cyclopropylthio, cyclopropylsulfinyl, cyclopropylsulfonyl, difluoromethylthio, difluoromethylsulfinyl, difluoromethylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl, trifluoromethylsulfonyl, and (4-chlorophenyl)sulfonyl, or R.sup.2 is pyridine which is optionally substituted by one to three substituents independently selected from the group consisting of fluorine, chlorine, bromine, iodine, —CN, —NO.sub.2, methyl, 1-cyano-1-methylethyl, difluoromethyl, trifluoromethyl, cyclopropyl, 1-cyanocyclopropyl, 1-(trifluoromethyl)cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, isopropylthio, isopropylsulfinyl, isopropylsulfonyl, cyclopropylthio, cyclopropylsulfinyl, cyclopropylsulfonyl, difluoromethylthio, difluoromethylsulfinyl, difluoromethylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl, and trifluoromethylsulfonyl, or R.sup.2 is thiophene, furane, pyrazole and thiazole each of which is optionally substituted by one or two substituents independently selected from the group consisting of fluorine, chlorine, bromine, iodine, —CN, —NO.sub.2, methyl, difluoromethyl, trifluoromethyl, cyclopropyl, 1-cyanocyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, ethylthio, ethylsulfinyl, ethylsulfonyl, isopropylthio, isopropylsulfinyl, isopropylsulfonyl, cyclopropylthio, cyclopropylsulfinyl, cyclopropylsulfonyl, difluoromethylthio, difluoromethylsulfinyl, difluoromethylsulfonyl, trifluoromethylthio, trifluoromethyl-sulfinyl, and trifluoromethylsulfonyl; R.sup.3a is hydrogen; R.sup.3b is selected from the group consisting of hydrogen, methyl, ethyl, iso-propyl, n-propyl, difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, and 2,2,2-trifluoroethyl; R.sup.4 is pyridine, pyrimidine, pyrazine or thiazole, wherein (A) the pyridine, pyrimidine or pyrazine is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, bromine, —CN, —NH.sub.2, —NO.sub.2, —COOH, —CONH.sub.2, —CSNH.sub.2, —CO.sub.2Me, methyl, ethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, cyclopropyl, methoxy, difluoromethoxy, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, difluoromethylthio, difluoromethylsulfinyl, difluoromethylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl, trifluoromethylsulfonyl, —NHCO-methyl, —NHCO-trifluoromethyl, —NHCO—CH.sub.2CN, —NHCO-cyclopropyl, —N(methyl)CO-cyclopropyl, —NHCO-1-cyanocyclopropyl, —NHSO.sub.2-methyl, —NHSO.sub.2-trifluoromethyl, —NHCO-phenyl, wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, bromine, —CN, methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy; —CONH-methyl, —CON(methyl).sub.2, —CON(methyl)-ethyl, —CONH—SO.sub.2-methyl, —CON(methyl)-SO.sub.2-methyl, —CONH-difluoroethyl, —CON(methyl)-difluoroethyl, —CONH-trifluoroethyl, —CON(methyl)-trifluoroethyl, —CONH-cyclopropyl, —CON—(N-methyl)-cyclopropyl, —CONH-cyanomethyl, —CON(methyl)-cyanomethyl, —CONH-1-cyanocyclopropyl, —CON(methyl)-1-cyanocyclopropyl, —CONH— phenyl, wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, bromine, —CN, methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy, and (B) the thiazole is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, bromine, —CN, —NO.sub.2, methyl, ethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, cyclopropyl, methoxy, difluoromethoxy, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, difluoromethylthio, difluoromethylsulfinyl, difluoromethylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl and trifluoromethylsulfonyl, or R.sup.4 is selected from the following substructure S18-1 or S18-2 in which the bond to the triazole is marked with a #: ##STR00526## R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached represent the heterocyclyl group pyrrolidine-1-yl, morpholin-4-yl, or 2,6-dimethylmorpholin-4-yl; R.sup.5 is —CH.sub.2—SO.sub.2-methyl, —CH.sub.2—COO-tert-butyl, —CH.sub.2—NH.sub.2, —CH.sub.2—NH—COO-methyl, —CH.sub.2—NH—CO-methyl, —CH.sub.2—NH—CO-trifluoromethyl, —CH.sub.2—NH—CO-cyclopropyl, —CN, —COOH, —CONH.sub.2, —CO—NH-methyl, —CO—NH-cyclopropyl, —CO—NH(CH.sub.2CH═CH.sub.2), —CO—NH(CH.sub.2CH═CF.sub.2), —CO—NH(CH.sub.2—C≡CH), —CO—NH-(1-fluoro-cyclopropyl), —NH.sub.2, —NH-methyl, dimethylamino, prop-2-enoylamino, methoxy(methyl)amino, —NH—CH.sub.2-cyclopropyl, —N-methyl-CO-methyl, —N-methyl-CO-tert-butyloxy, —N-methyl-CO-trifluoromethyl, —N-methyl-CO-cyclopropyl, —NHCO-methyl, —NHCO-methoxy, —NHCO-tert-butyloxy, —NHCO-trifluoromethyl, —NHCO-(2,2,2-trifluoroethyl), —NHCO-(1-chloroethyl), —NHCO-cyclopropyl, —NHCO-(1-chloro-cyclopropyl), —NHCO-(1-fluoro-cyclopropyl), —NHCO-(2-fluoro-cyclopropyl), —NHCO-(2,2-difluoro-cyclopropyl), —NHSO.sub.2-methyl, —NHSO.sub.2-trifluoromethyl, —N(SO.sub.2-methyl).sub.2, —NHSO.sub.2-cyclopropyl, —N-methyl-SO.sub.2-methyl, —N-methyl-SO.sub.2-trifluoromethyl, —N-methyl-SO.sub.2-cyclopropyl, methylthio, methylsulfinyl, methylsulfonyl, 2,2,2-trifluoroethylthio, 2,2,2-trifluoroethylsulfinyl, or heptafluoro-iso-propylthio, or R.sup.5 is pyrrolidine-1-yl, piperidin-1-yl or morpholin-4-yl, or R.sup.5 is benzyl, pyridine, pyrimidine, pyrazine, furane, optionally substituted with one to three substituents selected from the group consisting of fluorine, chlorine, —CN, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, —NO.sub.2, —NH.sub.2 and the following substituents each of which optionally further substituted: methyl, ethyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, trifluoromethoxy, difluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, or —NH—CO-methyl.

5. Compound according to claim 1, in which X is O; Y is a direct bond; R.sup.1 is hydrogen; R.sup.2 is 3,5-dichlorophenyl, 3,5-dibromophenyl, 3-bromo-5-chlorophenyl, 3-cyano-5-fluorophenyl, 3-chloro-5-cyanophenyl, 3-chloro-5-(trifluoromethyl)phenyl, 3-bromo-5-(trifluoromethyl)phenyl, 3,5-bis(trifluoromethyl)phenyl, 3-chloro-5-(trifluoromethoxy)phenyl, 3-bromo-5-(trifluoromethoxy)phenyl, 3-chloro-5-(methylsulfonyl)phenyl, 3-chloro-5-(difluoromethylsulfonyl)phenyl, 3-chloro-5-(trifluoromethylsulfonyl)phenyl, 3-methylsulfonyl-5-(trifluoromethyl)phenyl, 3-ethylsulfonyl-5-(trifluoromethyl)phenyl, 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-ethylsulfonyl-5-(trifluoromethoxy)phenyl, 3-isopropylsulfonyl-5-(trifluoromethoxy)phenyl, 3-cyclopropylsulfonyl-5-(trifluoromethoxy)phenyl, 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)phenyl, 3-(4-chlorophenyl)sulfonyl-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethylsulfonyl)phenyl, 3-bromo-5-[1-(trifluoromethyl)cyclopropyl]phenyl, 3-chloro-5-(1-cyano-1-methyl-ethyl)phenyl, 2,6-dichloropyridin-4-yl, 2-chloro-6-(trifluoromethyl)-pyridin-4-yl, 5-(trifluoromethyl)-pyridin-3-yl, or 1-methyl-5-(trifluoromethyl)-pyrazol-3-yl; R.sup.3a is H; R.sup.3b is methyl; R.sup.4 is pyrimidin-2-yl, 5-chloropyrimidin-2-yl, 5-chloropyridin-2-yl, 5-cyanopyridin-2-yl, 5-cyano-1,3-thiazol-2-yl, 5-carboxypyridin-2-yl, 5-(methoxycarbonyl)pyridin-2-yl, 5-(dimethylaminocarbonyl)pyridin-2-yl, 5-[[ethyl(methyl)amino]carbonyl]pyridin-2-yl, 5-[[cyclopropyl(methyl)amino]carbonyl]pyridin-2-yl, 5-[[cyclopropylmethyl(methyl)amino]carbonyl]pyridin-2-yl, 5-[(cyclopropylcarbonyl)(methyl)amino]-pyridin-2-yl, 5-(pyrrolidin-1-ylcarbonyl)pyridin-2-yl, 5-(morpholin-4-ylcarbonyl)pyridin-2-yl, 5-(morpholin-4-carbonyl)thiazol-2-yl], 5-[[rac-(2R,6R)-2,6-dimethylmorpholin-4-yl]carbonyl]pyridin-2-yl, or 5-[[(2R,6S)-2,6-dimethylmorpholin-4-yl]carbonyl]pyridin-2-yl; R.sup.5 is —NHCO-tert-butyloxy, —NH.sub.2, —N-methyl-CO-tert-butyloxy, —NHCO-methoxy, —NHCO-methyl, —NHCO-cyclopropyl, —NHCO-(1-chloro-cyclopropyl), —NHCO-(2-fluoro-cyclopropyl), —NHCO-(2,2-difluoro-cyclopropyl), —NHCO-(2,2,2-trifluoroethyl), —NHCO-(1-chloroethyl), —NHSO.sub.2-trifluoromethyl, —N(SO.sub.2-methyl).sub.2, —CH.sub.2—SO.sub.2-methyl, methylthio, methylsulfinyl, methylsulfonyl, 2,2,2-trifluoroethylthio, 2,2,2-trifluoroethylsulfinyl, heptafluoro-iso-propylthio, —CN, —COOH, —CONH.sub.2, —CO—NH-cyclopropyl, —CO—NH-methyl, 6-chloropyridin-3-yl, 5-pyrazin-2-yl, pyrimidin-2-yl, 2-furyl, benzyl, (2,6-difluorophenyl)methyl, (3,5-difluorophenyl)methyl, methylamino, dimethylamino, acetyl(methyl)amino, prop-2-enoylamino, methoxy(methyl)amino, pyrrolidine-1-yl, piperidin-1-yl, or morpholin-4-yl.

6. Compound according to claim 1, comprising a structure according to formula (I′) ##STR00527##

7. Compound according to claim 1, in which R.sup.2 is phenyl, pyridine, pyrimidine, pyrazine or pyridazine, wherein the phenyl, pyridine, pyrimidine, pyrazine or pyridazine is substituted with a total of one to three substituents, provided the substituent(s) are not on either carbon adjacent to the carbon bonded to the C═X group and at least one and up to two substituent(s) are independently selected from group A consisting of C.sub.1-C.sub.4-alkyl substituted by one to two substituents selected from the group consisting of —CN; and C.sub.3-C.sub.6cycloalkyl, wherein the C.sub.3-C.sub.6cycloalkyl is optionally substituted with halogen, —CN, C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-haloalkyl; C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylsulfinyl, and C.sub.1-C.sub.4haloalkylsulfonyl; phenylsulfanyl wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl and C.sub.1-C.sub.3haloalkoxy; phenylsulfinyl wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl and C.sub.1-C.sub.3haloalkoxy; phenylsulfonyl wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl and C.sub.1-C.sub.3haloalkoxy; and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl and C.sub.1-C.sub.3haloalkoxy; the other one to two optional substituent(s) are each independently selected from group B consisting of halogen, —CN, —NO.sub.2, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, and C.sub.1-C.sub.4haloalkylsulfonyl; or R.sup.2 is thiophene, furane, pyrazole, thiazole, isothiazole, oxazole or isoxazole each of which is optionally substituted by one to three substituents independently selected from the group consisting of halogen, hydroxy, —CN, —NO.sub.2; C.sub.1-C.sub.6alkyl optionally substituted by —CN; C.sub.3-C.sub.6cycloalkyl, optionally substituted by halogen, —CN, C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-haloalkyl; C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl; and phenyl and 5- to 6-membered heteroaryl, wherein the phenyl or 5- to 6-membered heteroaryl is optionally substituted with one to two substituents selected from the group consisting of halogen, —CN, C.sub.1-C.sub.3alkyl and C.sub.1-C.sub.3haloalkyl.

8. Compound according to claim 1, in which R.sup.4 is pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is substituted with two to three substituents independently selected from the group consisting of halogen, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, and C.sub.1-C.sub.4alkoxy; or R.sup.4 is pyridine, pyrimidine, pyrazine or pyridazine, wherein the pyridine, pyrimidine, pyrazine or pyridazine is substituted with a total of one to three substituent(s), provided at least one and up to three substituent(s) are independently selected from group A consisting of —COOH, —CN, —NO.sub.2, —NH.sub.2, C.sub.5-C.sub.6cycloalkyl, C.sub.3-C.sub.4cycloalkyl substituted by halogen, —CN, C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-haloalkyl; C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NHCS—C.sub.1-C.sub.4alkyl, —NHCS—C.sub.3-C.sub.5cycloalkyl, —NHCS—C.sub.1-C.sub.4alkyl-C.sub.3-C.sub.5cycloalkyl, —N(SO.sub.2C.sub.1-C.sub.4alkyl).sub.2, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONHSO.sub.2—C.sub.1-C.sub.4alkyl, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl; the other one to two optional substituent(s) are each independently selected from group B consisting of halogen, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, and C.sub.1-C.sub.4alkoxy, or R.sup.4 is a 5-membered heteroaryl optionally substituted with one to three substituents independently selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NHCO—C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CON(C.sub.1-C.sub.4alkyl).sub.2, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl; or R.sup.4 is pyridine, pyrimidine or thiazole, wherein the pyridine, pyrimidine or thiazole is substituted with a total of one to two substituent(s), provided at least one and up to two substituent(s) are independently selected from group A consisting of of following substructures S40, S41, and S42 in which the bond to the pyridine, pyrimidine or thiazole is marked with a # and Z is CO or SO.sub.2: ##STR00528## R.sup.46 is hydrogen or in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, —C.sub.1-C.sub.6alkyl-C.sub.3-C.sub.6cycloalkyl, phenyl, C.sub.1-C.sub.6alkyl-phenyl, heteroaryl, C.sub.1-C.sub.6alkyl-heteroaryl, heterocyclyl and C.sub.1-C.sub.6alkyl-heterocyclyl; R.sup.47 is hydrogen or in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.3-C.sub.6cycloalkyl, —C.sub.1-C.sub.6alkyl-C.sub.3-C.sub.6cycloalkyl, phenyl, C.sub.1-C.sub.6alkyl-phenyl, heteroaryl, C.sub.1-C.sub.6alkyl-heteroaryl, heterocyclyl and C.sub.1-C.sub.6alkyl-heterocyclyl; or R.sup.46 and R.sup.47 together with the nitrogen atom to which they are attached, represent a monocyclic, spirocyclic or bridged polycyclic 4- to 8-membered saturated heterocyclyl which may contain up to one further heteroatom selected from the group of oxygen, nitrogen and sulfur and which is optionally substituted with one to three substituents selected from the group consisting of halogen, ═O (oxo), ═S (thiono), hydroxy, and —CN; and —CO.sub.2—C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.4cycloalkylsulfanyl, C.sub.3-C.sub.4cycloalkylsulfinyl, C.sub.3-C.sub.4cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, —NHCO—C.sub.1-C.sub.3alkyl, —N(C.sub.1-C.sub.3alkyl)CO—C.sub.1-C.sub.3alkyl, —NHCO—C.sub.1-C.sub.3cycloalkyl, —N(C.sub.1-C.sub.3alkyl)CO—C.sub.3-C.sub.4cycloalkyl, —CO.sub.2C.sub.1-C.sub.3alkyl, —CONH(C.sub.1-C.sub.3alkyl), —CONH(C.sub.3-C.sub.4cycloalkyl), and —CON(C.sub.1-C.sub.3alkyl).sub.2, and the other one to two optional substituent(s) are each independently selected from group B consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3haloalkylsulfinyl, and C.sub.1-C.sub.3haloalkylsulfonyl.

9. Compound according to claim 1, in which R.sup.2 is the following substructure Q1, in which the bond to the C═O— group is marked with a #: ##STR00529## and wherein R.sup.21 is hydroxy, —NH.sub.2, —SO.sub.2NH.sub.2, C.sub.4-C.sub.6alkyl, C.sub.4alkoxy, C.sub.1-C.sub.3cyanoalkyl, C.sub.3C.sub.6cycloalkyl, C.sub.3-C.sub.6halocycloalkyl, C.sub.3-C.sub.6cyanocycloalkyl; C.sub.3-C.sub.6cycloalkyl, substituted by C.sub.1-C.sub.3haloalkyl; C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, C.sub.1-C.sub.3cyanoalkoxy, hydroxy-C.sub.1-C.sub.4alkyl, —NH(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl).sub.2, —NHCO—C.sub.1-C.sub.4alkyl, NHCO—C.sub.3-C.sub.6cycloalkyl, —NHSO.sub.2(C.sub.1-C.sub.4alkyl), —N(C.sub.1-C.sub.4alkyl)CO—C.sub.1-C.sub.4alkyl, —N(C.sub.1-C.sub.4alkyl)CO—C.sub.3-C.sub.6cyclolkyl, —N(C.sub.1-C.sub.4alkyl)SO.sub.2C.sub.1-C.sub.4alkyl, —N(SO.sub.2C.sub.1-C.sub.4alkyl).sub.2, —CO.sub.2C.sub.1-C.sub.4alkyl, —CONH(C.sub.1-C.sub.4alkyl), —CONH(C.sub.3-C.sub.6cycloalkyl), —CONH— phenyl, —CON(C.sub.1-C.sub.4alkyl).sub.2, —CON(C.sub.1-C.sub.4alkyl)(C.sub.3-C.sub.6cycloalkyl), —CON(C.sub.1-C.sub.4alkyl)-phenyl, —C(═NOC.sub.1-C.sub.4alkyl)H, —C(═NOC.sub.1-C.sub.4alkyl)-C.sub.1-C.sub.4alkyl, (C.sub.1-C.sub.4alkyl).sub.3-silyl, —SO.sub.2NH(C.sub.1-C.sub.4alkyl), phenylsulfonyl, or 3- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein phenyl groups of the aforementioned substituents and the 3- to 6-membered heterocyclyl substituent may optionally carry 1, 2 or 3 substituents independently selected from the group consisting of halogen, —CN, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl and C.sub.1-C.sub.3cyanoalkyl; and R.sup.22 is halogen, —CN, —COOH, —CONH.sub.2, —NO.sub.2, —SF.sub.5, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3haloalkylthio, C.sub.1-C.sub.3alkylthio, C.sub.1-C.sub.3alkylsulfinyl, C.sub.1-C.sub.3alkylsulfonyl, C.sub.1-C.sub.3haloalkylsulfinyl, C.sub.1-C.sub.3haloalkylsulfonyl, C.sub.3-C.sub.6cycloalkylsulfanyl, C.sub.3-C.sub.6cycloalkylsulfinyl, C.sub.3-C.sub.6cycloalkylsulfonyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.3cyanoalkyl, or C.sub.3-C.sub.6cyanocycloalkyl.

10. Compound of formula (a) ##STR00530## wherein R.sup.1 is hydrogen, R.sup.3b is methyl, R.sup.3a is hydrogen and Y is a direct bond and wherein R.sup.4 and R.sup.5 R.sup.4 is pyridine, pyrimidine, pyrazine or thiazole, wherein (A) the pyridine, pyrimidine or pyrazine is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, bromine, —CN, —NH.sub.2, —NO.sub.2, —COOH, —CONH.sub.2, —CSNH.sub.2, —CO.sub.2Me, methyl, ethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, cyclopropyl, methoxy, difluoromethoxy, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, difluoromethylthio, difluoromethylsulfinyl, difluoromethylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl, trifluoromethylsulfonyl, —NHCO-methyl, —NHCO-trifluoromethyl, —NHCO—CH.sub.2CN, —NHCO-cyclopropyl, —N(methyl)CO-cyclopropyl, —NHCO-1-cyanocyclopropyl, —NHSO.sub.2-methyl, —NHSO.sub.2-trifluoromethyl, —NHCO-phenyl, wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, bromine, —CN, methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy; —CONH-methyl, —CON(methyl).sub.2, —CON(methyl)-ethyl, —CONH—SO.sub.2-methyl, —CON(methyl)-SO.sub.2-methyl, —CONH-difluoroethyl, —CON(methyl)-difluoroethyl, —CONH-trifluoroethyl, —CON(methyl)-trifluoroethyl, —CONH-cyclopropyl, —CON—(N-methyl)-cyclopropyl, —CONH— cyanomethyl, —CON(methyl)-cyanomethyl, —CONH-1-cyanocyclopropyl, —CON(methyl)-1-cyanocyclopropyl, —CONH— phenyl, wherein the phenyl is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, bromine, —CN, methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy and trifluoromethoxy, and (B) the thiazole is optionally substituted with one to two substituents selected from the group consisting of fluorine, chlorine, bromine, —CN, —NO.sub.2, methyl, ethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, cyclopropyl, methoxy, difluoromethoxy, trifluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, difluoromethylthio, difluoromethylsulfinyl, difluoromethylsulfonyl, trifluoromethylthio, trifluoromethylsulfinyl and trifluoromethylsulfonyl, or R.sup.4 is selected from the following substructure S18-1 or S18-2 in which the bond to the triazole is marked with a #: ##STR00531## R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached represent the heterocyclyl group pyrrolidine-1-yl, morpholin-4-yl, or 2,6-dimethylmorpholin-4-yl, R.sup.5 is —CH.sub.2—SO.sub.2-methyl, —CH.sub.2—COO-tert-butyl, —CH.sub.2—NH.sub.2, —CH.sub.2—NH—COO-methyl, —CH.sub.2—NH—CO-methyl, —CH.sub.2—NH—CO-trifluoromethyl, —CH.sub.2—NH—CO-cyclopropyl, —CN, —COOH, —CONH.sub.2, —CO—NH-methyl, —CO—NH-cyclopropyl, —CO—NH(CH.sub.2CH═CH.sub.2), —CO—NH(CH.sub.2CH═CF.sub.2), —CO—NH(CH.sub.2—C≡CH), —CO—NH-(1-fluoro-cyclopropyl), —NH.sub.2, —NH-methyl, dimethylamino, prop-2-enoylamino, methoxy(methyl)amino, —NH—CH.sub.2-cyclopropyl, —N-methyl-CO-methyl, —N-methyl-CO-tert-butyloxy, —N-methyl-CO-trifluoromethyl, —N-methyl-CO-cyclopropyl, —NHCO-methyl, —NHCO-methoxy, —NHCO-tert-butyloxy, —NHCO-trifluoromethyl, —NHCO-(2,2,2-trifluoroethyl), —NHCO-(1-chloroethyl), —NHCO-cyclopropyl, —NHCO-(1-chloro-cyclopropyl), —NHCO-(1-fluoro-cyclopropyl), —NHCO-(2-fluoro-cyclopropyl), —NHCO-(2,2-difluoro-cyclopropyl), —NHSO.sub.2-methyl, —NHSO.sub.2-trifluoromethyl, —N(SO.sub.2-methyl).sub.2, —NHSO.sub.2-cyclopropyl, —N-methyl-SO.sub.2-methyl, —N-methyl-SO.sub.2-trifluoromethyl, —N-methyl-SO.sub.2-cyclopropyl, methylthio, methylsulfinyl, methylsulfonyl, 2,2,2-trifluoroethylthio, 2,2,2-trifluoroethylsulfinyl, or heptafluoro-iso-propylthio, or R.sup.5 is pyrrolidine-1-yl, piperidin-1-yl or morpholin-4-yl, or R.sup.5 is benzyl, pyridine, pyrimidine, pyrazine, furane, optionally substituted with one to three substituents selected from the group consisting of fluorine, chlorine, —CN, —COOH, —CONH.sub.2, —SO.sub.2NH.sub.2, —NO.sub.2, —NH.sub.2 and the following substituents each of which optionally further substituted: methyl, ethyl, cyclopropyl, trifluoromethyl, difluoromethyl, methoxy, trifluoromethoxy, difluoromethoxy, methylthio, methylsulfinyl, methylsulfonyl, or —NH—CO-methyl.

11. Compound of formula (b-1) ##STR00532## wherein R.sup.2 is difluoromethylsulfanyl, difluormethylsulfinyl, or difluoromethylsulfonyl.

12. Formulation, optionally an agrochemical formulation, comprising at least one compound of the formula (I) according to claim 1.

13. Formulation according to claim 12, further comprising at least one extender and/or at least one surface-active substance.

14. Formulation according to claim 12, wherein at the compound of the formula (I) is in a mixture with at least one further active compound.

15. Method for controlling one or more pests, optionally animal pests, comprising allowing a compound of the formula (I) according to claim 1 or a formulation thereof to act on the pests and/or a habitat thereof.

16. Method according to claim 15, wherein the pest is an animal pest and comprises an insect, an arachnid or a nematode, or in that the pest is an insect, an arachnid or a nematode.

17. A product comprising a compound of formula (I) according to claim 1 or a formulation thereof for controlling one or more animal pests.

18. The product according to claim 17, wherein the animal pest comprises an insect, an arachnid or a nematode, or in that the animal pest is an insect, an arachnid or a nematode.

19. The product according to claim 17 in crop protection.

20. The product according to claim 17 in the field of animal health.

21. Method for protecting seed or a germinating plant from one or more, optionally animal pests, comprising contacting the seed with a compound of the formula (I) according to claim 1 a formulation thereof 14, whereas methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body are excluded.

22. Seed obtained by a method according to claim 21.

Description

DESCRIPTION OF THE PROCESSES AND INTERMEDIATES

[0955] Compounds of formula I′ may be prepared as illustrated in the following scheme 1 where R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5 and Y are as previously defined and X stands for OH or Cl.

##STR00049##

[0956] X═OH: An azole compound of formula (a) is reacted with a carboxylic acid of formula (b) (X═OH) to form compounds of formula I′. For example, a mixture of an azole of formula (a), a carboxylic acid of formula (b) (X═OH), a suitable coupling reagent, such as T3P®, HATU, DCC or HOBt, a suitable base such as triethylamine or DIPEA, in a suitable solvent, such as ethyl acetate or DMF are mixed at temperatures ranging from around 0 to 100° C. to provide compounds of formula I′ which may then be isolated and, if necessary and desired, purified using techniques well known in the art, such as chromatography.

[0957] X═Cl: An azole compound of formula (a) is reacted with a carboxylic acid chloride of formula (b) (X═Cl) to form compounds of formula I′. For example, a mixture of an azole of formula (a), a carboxylic acid chloride of formula (b) (X═Cl), a suitable base such as triethylamine or DIPEA, in a suitable solvent, such as dichloromethane or THF are mixed at temperatures ranging from around 0 to 100° C. to provide compounds of formula I′ which may then be isolated and, if necessary and desired, purified using techniques well known in the art, such as chromatography.

[0958] Carboxylic acids of formula (b) (X═OH) and carboxylic acid chlorides of formula (b) (X═Cl) are commercially available or may be synthesized by methods known to a person skilled in the state of the art.

[0959] For example, the carboxylic acids can be synthesized in analogy to WO 2016198507, WO 2015084936, WO 2015148354 and WO 2015148373.

[0960] Compounds of formula I″d may be prepared as illustrated in the following scheme 2, where R.sup.1, R.sup.2, R.sup.3, R.sup.3b, R.sup.5, R.sup.41 and Y are as previously defined. T is R.sup.4 as previously described and at least substituted with one NO.sub.2, —NH.sub.2, —NHA.sup.1 or -NA.sup.1A.sup.2 group respectively. LG is suitable leaving group and A.sup.1 and A.sup.2 represent R.sup.41Z—, R.sup.41Y.sup.1—, R.sup.41OCO—, R.sup.44OCO—, R.sup.42 and R.sup.43Y.sup.1—. Z and Y.sup.1 are CO or SO.sub.2. R.sup.42, R.sup.43 and R.sup.44 are in each case optionally substituted C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.6alkyl, phenyl-C.sub.1-C.sub.6alkyl, naphthyl-C.sub.1-C.sub.6alkyl;

##STR00050##

[0961] A nitro compound of formula (I″a) is converted into the respective amino compound of formula (I″b) under reducing conditions, likewise with hydrogen and palladium on charcoal in a suitable solvent like THF or ethanol (European Journal of Medicinal Chemistry, 158, 322-333; 2018), with tin(II) chloride and HCl in a suitable solvent like ethanol (WO 2018085247), with iron powder and HCl in a suitable solvent like ethanol (WO 2017216293) or with iron powder in a mixture of acetic acid and ethanol. The resulting amino compound (I″b) reacts, in the presence of a suitable base such as DIPEA or potassium carbonate, with chloroformates or acylation, benzoylation, sulfonylation or alkylation reagents of formula A.sup.1-LG (c.sup.1) or A.sup.2-LG (c.sup.2). If one equivalent of A.sup.1-LG (c.sup.1) is used compounds of formula (I″c) are obtained. Further treatment with one equivalent of A.sup.2-LG (c.sup.2) yields compounds of formula (I″d). The obtained compounds of formula (I″c) and (I″d) are then if necessary and desired, purified using techniques well known in the art, such as chromatography.

[0962] Compounds of formula I″e may be prepared as illustrated in the following scheme 3, where R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.5, R.sup.41, R.sup.42, R.sup.45 and Y are as previously defined, wherein T is R.sup.4 as previously described and at least substituted with one —CO.sub.2alkyl-group, —COOH or —CONE.sup.1E.sup.2 group respectively. —NE.sup.1E.sup.2 represents —NR.sup.41R.sup.42, —NR.sup.41R.sup.41, —NR.sup.45NR.sup.41R.sup.45, —NR.sup.41NR.sup.45R.sup.45, —NR.sup.45NR.sup.45R.sup.45, —NR.sup.41NR.sup.45R.sup.41, —NR.sup.41OR.sup.45, —NR.sup.45OR.sup.45 and —NR.sup.45OR.sup.41. R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached may also represent a heterocyclyl as previously defined.

##STR00051##

[0963] An ester compound of formula (I″e) is saponified to obtain the respective carboxylic acid compound of formula (I″f) followed by an amide coupling step with amines, hydrazines or substituted hydroxylamines of formula (d) to obtain amides of formula (I″g) by methods known to a person skilled in the state of the art.

[0964] For example, a mixture of an amine, hydrazine or substituted hydroxylamine of formula (d), a carboxylic acid (I″f), a suitable coupling reagent, such as T3P®, HATU, DCC or HOBt, a suitable base such as triethylamine or DIPEA, in a suitable solvent such as ethyl acetate or DMF are mixed at temperatures ranging from around 0 to 100° C. to provide compounds of formula (I″g) which may then be isolated and, if necessary and desired, purified using techniques well known in the art, such as chromatography.

[0965] Scheme 4 illustrates the preparation 3-N-Boc-amino or 3-amino-1,2,4-triazoles (I″h) and (I″i) starting with 3-N-Boc-amino-1,2,4-triazole containing amines (j) (see examples 1-001 to 1-008). R.sup.1 is hydrogen, R.sup.3a is methyl, R.sup.3b is hydrogen, X is oxygen, Y is a direct bond, R.sup.5 is N-Boc-amino or amino and R.sup.2 as well as R.sup.4 have the meanings given in of formula I.

##STR00052##

[0966] In a first step, ((αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (e) (Pht-Ala-OH purchased from ABCR) reacts with 1-N-Boc-2-methyl-isothiourea (f) (purchased from ABCR) in the presence of a base and the coupling reagent HATU to form the N-acylated 1-N-Boc-2-methyl-isothiourea (g). Thereby a partially or fully racemization is possible. In a second step the cyclization occurs with R.sup.4-substituted hydrazines (h) and in the presence of a base, like pyridine, as described in WO 2014009425 A1 to form the 3-N-Boc-amino-substituted 1,2,4-triazoles of formula (i). In the third step the phthalimide protecting group is cleaved with hydrazine hydrate in a suitable solvent, like ethanol, as described in WO 2018/086605. Then, in a fourth step, the obtained N-Boc-protected amines (j) react with different carboxylic acids (k) to form the compounds (I″h). After N-Boc-deprotection in the fifth step under acidic conditions (HCl in dioxane) 3-amino-substituted 1,2,4-triazoles (I″i) are obtained as described in scheme 4.

[0967] Scheme 5 illustrates the preparation of amines (ja) containing 3-alkyl- or 3-haloalkyl Boc protected amino rests which are intermediates in the synthesis of, e.g., example I-009.

##STR00053##

[0968] In a first step, tert-butoxycarbonyl tert-butyl carbonate reacts with a salt of N-alkyl or N-haloalkyl methyl-isothiourea hydrohalogenide (fa) e.g. hydroiodide, in presence of NaHCO.sub.3 to form the N-alkyl or N-haloalkyl tert-butyl N-(methylsulfanylcarbonimidoyl)carbamates (fb) which reacts with (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (e) in a second step in the presence of a base and the coupling reagent HATU to form the N-acylated N-alkyl or N-haloalkyl tert-butyl N-(methylsulfanylcarbonimidoyl) carbamates (ga). Thereby a partially or fully racemization is possible. In a third step the cyclization of (ga) occurs with R.sup.4-substituted hydrazines (h) in the presence of a base, like pyridine, as described in WO 2014009425 A1 to form the 1,2,4-triazoles of formula (ia). In the last step the phthalimide protecting group is cleaved with hydrazine hydrate in a suitable solvent, like ethanol, as described in WO 2018/086605 to form the corresponding amines (ja) wearing 3-alkyl- or 3-haloalkyl-3-N-Boc-amino groups as a substituents at the triazole core.

[0969] The N-methyl-carbamimidothioic acid methyl ester are either commercially available or may be synthesized by methods known to the person skilled in the art.

[0970] For example:

[0971] For N-Methyl-carbamimidothioic acid methyl ester, hydriodide (1:1), see CAS-no: 41306-45-0 (ABCR, WO 2006138350); R=methyl.

[0972] For N-Ethyl-carbamimidothioic acid methyl ester, hydriodide (1:1), see CAS-no: 7204-32-2 (Milestone Pharmtech Product List, WO 2009115515); R=ethyl.

[0973] For N-Propyl-carbamimidothioic acid methyl ester, see CAS-no: 925-59-7 (Chemieliva Pharmaceutical Product List; S. Pockes, et al., ACS Omega, 3(3), 2865-2882; 2018); R=propyl.

[0974] For 1-Methylethyl-carbamimidothioic acid methyl ester, monohydrochloride, see CAS-no: 5734-00-9, Shanghai Chemhere Product List; S. Pockes, et al., ACS Omega, 3(3), 2865-2882; 2018); R=iso-propyl.

[0975] For 2-Propenyl-carbamimidothioic acid methyl ester, see CAS-no: 50420-33-2, FCH Group Reagents for Synthesis); R=allyl.

[0976] Scheme 6 illustrates the synthesis of amines (jb) wearing 3-alkylsulfonylamino, 3-cycloalkylsulfonylamino or 3-halogenalkylsulfonylamino groups as substituents at the triazole ring, which are used as intermediates.

##STR00054##

[0977] In a first step, alkyl, cycloalkyl or halogenalkylsulfonyl chlorides (1) react with methyl carbamimidothioate sulfate (fc) in presence of Na.sub.2CO.sub.3 to form the 1-N-alkyl, cycloalkyl or halogenalkylsulfonyl-2-methyl-isothioureas (fd) which reacts with (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (e) in a second step in the presence of a base and the coupling reagent HATU to form the N-acylated 1-N-alkyl, cycloalkyl or halogenalkylsulfonyl-2-methyl-isothioureas (gb). Thereby a partially or fully racemization is possible. In a third step the cyclization occurs with R.sup.4-substituted hydrazines (h) and in the presence of a base, like pyridine, as described in WO 2014009425 A1 to form the 1,2,4-triazoles of formula (ib). In the last step the phthalimide protecting group is cleaved with hydrazine hydrate in a suitable solvent, like ethanol, as described in WO 2018/086605 to form the 3-alkyl, 3-cycloalkyl or 3-halogenalkylsulfonylamino-1,2,4-triazole amines (jb), which can be uses as intermediates (e.g. INT-004 with R.sup.5═NH—SO.sub.2CHF.sub.2).

[0978] Scheme 7 illustrates the preparation of 3-carbamoylamino, 3-acylamino or 3-sulfonylamino 1,2,4-triazoles (I″k) to (I″m) starting from the examples I-006 to I-008.

##STR00055##

[0979] The 3-amino-substituted 1,2,4-triazoles (l″j) react e.g. with aryl or alkyl chloroformates, acyl chlorides or corresponding anhydrides and aryl or alkylsulfonyl chlorides in presence of base and a solvent, to form 3-carbamoylamino, 3-acylamino or 3-sulfonylamino 1,2,4-triazoles (I″k) to (I″m) as exemplified with I-010 (3-N-carbamoylamino-1,2,4-triazoles), I-012 to I-024 (3-N-acylamino-1,2,4-triazoles) and I-025 (3-N-sulfonylamino-1,2,4-triazole).

[0980] The aryl or alkyl chloroformates, acyl chlorides or corresponding anhydrides and aryl or alkylsulfonyl chlorides are either commercially available or may be synthesized by methods known to the skilled artisan.

[0981] cheme 8 illustrates the preparation of 3-methylsulfonylmethylen or 3-hetaryl 1,2,4-triazole amines (jc) used for the synthesis of e.g. examples I-027 to I-058.

##STR00056##

[0982] In a first step, a hydrazone amide (n) is formed from R.sup.4-substituted hydrazines (h) and (m) as described in EP 1099695. In a second step hydrazine amine (n) reacts with (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetyl chloride (ea), prepared from (αS)-1,3-dihydro-ax-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (e)) and oxalyl chloride according to Tetrahedron: Asymmetry, 21(8), 936-942, 2010, in the presence of a base, like pyridine, as described in EP 1099695 to form triazoles (ic). Thereby a partially or fully racemization is possible. In a third step, the phthalimide protecting group is cleaved with hydrazine hydrate in a suitable solvent, like ethanol, as described in WO 2018086605. In a final step, the obtained 3-methylsulfonylmethylen or 3-hetaryl-1,2,4-triazole amines (jc) react as intermediates INT-005 to INT-011 with different carboxylic acids to form the example compounds, e.g. examples I-027 to I-058 as described in scheme 1.

[0983] The imidic acid alkyl ester (m) are either commercially available or may be synthesized by methods known to the skilled artisan.

[0984] For example:

[0985] For 2-(methylsulfonyl)-ethanimidic acid ethyl ester hydrochloride (1:1), see W. Tang, et al., J. Amer. Chem. Soc. 137(18), 5980-5989, 2015 (used for R.sup.5═CH.sub.2—SO.sub.2-Me; intermediate INT 005, examples I-027 to I-030)

[0986] For 6-chloro-3-pyridinecarboximidic acid methyl ester, see WO 2009105500 A1 (used for R.sup.5=6-chloro-3-pyridyl; intermediates INT 006 and INT 008, examples I-031 to I-033)

[0987] For 2-pyrazinecarboximidic acid methyl ester, see EP 388528 A2 (used for R.sup.5=2-pyrazinyl; intermediates INT 007 and INT 009, examples I-034 to I-040)

[0988] For 2-pyrimidinecarboximidic acid methyl ester, see WO 2012048129 A2 (used for R.sup.5=2-pyrimidinyl; intermediate INT 010, examples I-051 to I-056)

[0989] For 2-furancarboximidic acid methyl ester hydrochloride (1:1), see WO 2013066684 A1 (used for R.sup.5=2-furanyl; intermediate INT 011, examples I-057 and I-058)

[0990] Scheme 9 illustrates the preparation of amines (jd) substituted with different sulfides at the triazol ring which are used as intermediates in the synthesis of e.g. examples I-059, I-062, I-065, I-067 and I-069.

##STR00057##

[0991] In a first step (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetyl chloride (ea), prepared from (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (e) and oxalyl chloride, reacts with the ammonium thiocyanate in acetonitrile at room temperature as described by M. M. Hemdan, et al. Phosphorus, Sulfur and Silicon and the Related Elements 187(2), 181-189, 2012 to form the phthalimidoacyl isothiocyanate (eb), which was used without further purification. In a second step isothiocyanate (eb) reacts with R.sup.4-substituted hydrazines (h) to form intermediates (ec) which cyclize in situ to intermediates (id) by heating the reaction mixture (see M. M. Hemdan, et al. Phosphorus, Sulfur and Silicon and the Related Elements 187(2), 181-189, 2012). Thereby a partially or fully racemization is possible. In a fourth step, the 5-thioxo-1H-1,2,4-triazoles of formula (id) react with alkyl or halogen alkyl halides (r) in the presence of a base, like sodium hydride, to form 5-methylsulfanyl-1,2,4-triazoles of formula (ie). In a fifth step, the phthalimide protecting group is cleaved with hydrazine hydrate in a suitable solvent, like ethanol, as described in WO 2018086605. In a final step, the amine intermediates (jd) INT-012 to INT-014 react with different carboxylic acid to form the example compounds, e.g. I-059, I-062, I-065, I-067 and I-069 as described in scheme 1.

[0992] Scheme 10 illustrates the preparation of 3-alkylsulfinyl or 3-halogenalkylsulfinyl-1,2,4-triazoles (I″o) and 3-alkylsulfonyl or 3-halogenalkylsulfonyl-1,2,4-triazoles (I″p) starting from 3-alkylthio or 3-halogenalkylthio-1,2,4-triazoles (I″n).

##STR00058##

[0993] A 3-sulfanyl group (or 3-alkylthio group) containing 1,2,4-triazoles of formula (I″n) reacts with an oxidizing reagent such as 3-chloroperoxybenzoic acid or ruthenium(III) chloride in combination with sodium periodate to form 1,2,4-triazoles substituted with sulfoxides (I″o) or sulfones (I″p), at triazole ring, depending on the equivalents of the oxidizing reagent used, as exemplied by 1-060, 1-061, I-063, 1-064, 1-066 and I-068.

[0994] Scheme 11 illustrates the preparation of N-substituted 1,2,4-triazole-3-carboxamides (I″o) starting from methyl-1,2,4-triazole-3-carboxylates (q).

##STR00059##

[0995] In a first step, amino acids like L-alanine react with different leaving group (LG)-activated carboxylic acids (ka) (e.g. LG=halogen) in presence of a base, to form the N-acylated L-alanines (p) which react in a second step, with methyl 2-amino-2-imino-acetate hydrochloride (see CAS-no: 60189-97-1, ABCR) in presence of DIPEA and HATU, followed by cyclization with R.sup.4-substituted hydrazines (h) in the presence of acetic acid to afford the methyl-1,2,4-triazole-3-carboxylates of formula (q) (see G. M. Castanedo et al. J. Org. Chem., 76(4), 1177-1179, 2011). Thereby a partially or fully racemization is possible. In the third step the N-substituted 1,2,4-triazole-3-carboxamides (I″q) were formed by reaction of intermediates q with different amines and aluminium trimethyl (AlMe.sub.3) in a suitable solvent, like dichloromethane or toluene (J. Li, et al., Org. Lett., 14(1), 214-217, 2012) as demonstrated by the examples I-076 to I-079.

[0996] The (2S)-2-[[substituted-benzoyl]amino]propanoic acids (p) (N-acylated L-alanines) are either commercially available or may be synthesized by methods known to the skilled artisan (e.g. WO 2017148967).

[0997] For example:

[0998] For (2S)-2-{[3-bromo-5-chloro-phenyl]formamido}propanoic acid, see CAS-no: 1689965-18-1 (Aurora Building Blocks 3)

[0999] For (2S)-2-{[3,5-dichloro-phenyl]formamido}propanoic acid, see CAS-no: 1101188-46-8 (Aurora Building Blocks 3).

[1000] For (2S)-2-{[3-chloro-5-(trifluoromethyl)phenyl]formamido}propanoic acid, see CAS-no: 1938896-54-8 (FCH Group Premium Screening Compounds).

[1001] Scheme 12 illustrates the preparation of 1,2,4-triazole-3-carboxylic acids (I″r), 1,2,4-triazole-3-carboxamides (I″qa) and 3-cyano-1,2,4-triazoles (I″s) starting from methyl-1,2,4-triazole-3-carboxylates (q).

##STR00060##

[1002] In a first step methyl-1,2,4-triazole-3-carboxylates of formula (q) are saponified with NaOH in a mixture of MeOH and water to form the corresponding 1,2,4-triazole-3-carboxylic acids (I″r). In a second step, the 1,2,4-triazole-3-carboxylic acids (I″r) react with HATU in DMF and ammonium chloride in presence of a base (DIEA) at room temperature to give 1,2,4-triazole-3-carboxamides of formula (I″qa) which can be transformed then to the corresponding 3-cyano-1,2,4-triazoles of formula (I″s) by using dehydrating agents such as trifluoroacetic acid anhydride (TFAA) and a base (triethylamine or pyridine; see WO 2009137742) as demonstrated by the examples I-080 to I-081.

[1003] Scheme 13 illustrates the alternative preparation of 3-cyano-1,2,4-triazoles (I″s) starting from 3-N-Boc-amino or 3-amino-1,2,4-triazoles (I″h) and (I″i).

##STR00061##

[1004] After N-Boc-deprotection of the 1,2,4-triazoles of formula (I″h) under acidic conditions (HCl in dioxane) the corresponding 3-amino-1,2,4-triazoles (I″i) can be treated with tert-butyl nitrite and afterwards with a copper halides as salts, like CuCl.sub.2 (Hal=Cl) described by N. Desroy et al., J. Med. Chem. 2013, 56, 1418-1430, CuBr.sub.2 (Hal=Br) described in JP-Pat. 2010070503 A, CuI/I.sub.2 mixture (Hal=I) as described by K. Pchalek and M. P. Hay J. Org. Chem., 2006, 71, 6530-6535, or with diiodomethane (Hal=I) as described by N. R. Norcross et al. J. Med. Chem., 2016, 59(13), 6101-6120 to form the 3-halogen-substituted 1,2,4-triazoles (r). In a third step, the halogen can be replaced by the —CN group in the presence of zinc cyanide and tetrakis(triphenylphosphin)palladium(0) as described in WO 2018011628, forming the 3-cyano-1,2,4-triazoles (I″s) as demonstrated by the example I-071.

[1005] Scheme 14 illustrates the preparation of 3-aryl or 3-arylalkyl containing amines (je) (see INT-015 to INT-017) as used as intermediates for the synthesis of e.g. examples I-082 to I-085.

##STR00062##

[1006] In the same way as described in Scheme 13 the phthalimide protected 3-N-Boc-amino-1,2,4-triazoles of formula (i) can be transformed in a two-step reaction to form the 3-halogen-1,2,4-triazoles of formula (ig). In the third step, cross-coupling reactions (L.-Ch. Campeau and N. Hazari, Organometallics 38(1), 3-35, 2019; J. Carreras, et al., Chemistry—An Asian Journal 14(3), 329-343, 2019) in 3-position of the 1,2,4-triazoles (ig) are possible with aryl boronic acids as described in WO 2016081807 or arylalkyl zinc bromides as described in WO 2015164573 in the presence of tetrakis(triphenylphosphine) palladium(0), leading to R.sup.5-substituted 1,2,4-triazoles (ih). In a fourth step, the phthalimide protecting group is cleaved with hydrazine hydrate in a suitable solvent, like ethanol, as described in WO 2018086605. In a final step, the obtained 3-aryl or 3-arylalkyl containing 1,2,4-triazole amine intermediates (je) (INT-015 to INT-017) react with different carboxylic acid to form the example compounds, e.g. I-082 as described in scheme 1.

[1007] The boronic acids or arylalkyl zinc bromides are either commercially available or may be synthesized by methods known to the skilled artisan.

[1008] For bromo(phenylmethyl)-zinc, 0.5M in THF, see CAS-no: 62673-31-8 (ABCR).

[1009] For bromo(1-phenylethyl)-zinc, 0.5M in THF, see CAS-no: 85459-20-7 (ABCR).

[1010] For bromo[(2,6-difluorophenyl)methyl]-zinc, 0.5M in THF, see CAS-no: 307496-33-9 (ABCR).

[1011] For bromo[(3,5-difluorophenyl)methyl]-zinc, 0.5M in THF, see CAS-no: 308796-30-7 (ABCR).

[1012] For bromo[2-(1,1-dimethylethoxy)-2-oxoethyl]-zinc, 0.5M in diethyl ether, see CAS-no: 51656-70-3 (ABCR).

[1013] The preparation and use examples which follow illustrate the invention without limiting it.

[1014] Scheme 15 illustrates the preparation 3-haloalkylamino or 3-alkylamino-1,2,4-triazoles (I″t) starting with 3-alkylamino-1,2,4-triazole or 3-haloalkylamino-1,2,4-triazole containing Boc-protected amines (ib) as intermediates (see INT-020 and INT-021).

##STR00063##

[1015] In a first step, di-tert-butyl dicarbonate reacts with a salt of N-alkyl or N-haloalkyl methyl-isothiourea hydrohalogenides (fa) e.g. available as hydroiodide salt, in presence of a base like NaHCO.sub.3, to form N-alkyl or N-haloalkyl tert-butyl N-(methylsulfanylcarbonimidoyl)carbamates (fb) which react with N-Boc-alanine (ea) in a second step in the presence of a base and the coupling reagent HATU to form the N-acylated N-alkyl or N-haloalkyl tert-butyl N-(methylsulfanylcarbonimidoyl) carbamates (gb), which can be used without purification. In a third step the cyclization of (gb) occurs with R.sup.4-substituted hydrazines (h) and in the presence of an acid, like acetic acid to form the 1,2,4-triazoles of formula (ib), wherein R.sup.5 is NR-Boc. In a fourth step, both N-Boc protection groups are removed from the 1,2,4-triazoles of formula (ib), wherein R.sup.5 is NR-Boc by reaction with 4N HCl in dioxane to form the 3-alkyl- or 3-haloalkyl-amino-1,2,4-triazole containing amines or the related hydrochloride salt (jb) (see INT-020, INT-021, INT-024, INT-029 and INT-034) as demonstrated by the example compounds 1-126 to 1-132, 1-136,1-137, 1-142 to 1-143, 1-180 to 1-186, 1-202, I-206 to 1-210, 1-212, 1-217 to 1-219, 1-223, 1-226 to 1-228 and 1-231.

[1016] The N-methyl-carbamimidothioic acid methyl ester are either commercially available or may be synthesized by methods known to the skilled artisan (see Scheme 5).

[1017] Scheme 16 illustrates the preparation of 3-(N,N-dialkyl)-amino-, 3-(N-alkyl-N-cycloalkyl)-amino- or 3-heterocyclyl substituted 1,2,4-triazoles (I″u) starting with 3-(N,N-dialkyl)-amino, 3-(N-alkyl-N-cycloalkyl)-amino- or 3-heterocyclyl-1,2,4-triazole containing amines (jc) as intermediates (see INT-022 to INT-024). R.sup.1 is hydrogen, R.sup.3a is methyl, R.sup.3b is hydrogen, X is oxygen, Y is a direct bond, R.sup.5 is T.sup.1=NR.sup.51R.sup.52 and R.sup.2 as well as R.sup.4 have the meanings given in of formula I.

##STR00064##

[1018] In a first step, N-Boc-alanine (ea) reacts for example with N,N-dialkyl-carbamimidothioic acid methyl ester (fc; T.sup.1=-N(alkyl).sub.2) or 4-morpholinecarboximidothioic acid methyl ester (fc; T.sup.1=morpholinyl) in the presence of a base and a coupling reagent like HATU to form the N-acylated tert-butyl N-[(1S)-2-[[N,N-dialkylamino(methylsulfanyl)methylene]amino]-1-methyl-2-oxo-ethyl] carbamates (gc; T.sup.1=-N(alkyl).sub.2) or N-[(1S)-2-[[morpholino(methylsulfanyl)methylene]amino]-1-methyl-2-oxo-ethyl] carbamate acetic acid (fc; T.sup.1=morpholinyl) which can be used without further purification. In a second step the cyclization of (gc) occurs with R.sup.4-substituted hydrazines (h) and in the presence of an acid, like acetic acid to form the 1,2,4-triazoles of formula (ic). In the third step the N-Boc protection group is removed from the 1,2,4-triazoles of formula (ic), by reaction with 4N HCl in dioxane to form the 3-(N,N-dialkyl)- or morpholino-1,2,4-triazole containing amines or the related hydrochloride salt (ic) (see INT-022 to INT-023, INT-027, INT-028, INT-031 to INT-033, INT-036 and INT-037), as demonstrated by the example compounds I-138 to I-141, I-156, I-157, I-162, I-164 to I-166, I-170, I-171, I-176 to I-179, I-191 to I-194, I-229, I-232 to I-240 and I-252 to I-272 (T.sup.1=-N(CH.sub.3).sub.2), I-145 to I-147, I-158 to I-161, I-174, I-175, I-195, I-197, I-199, I-201, I-204 (T.sup.1=morpholinyl), I-196, I-198, I-200 and I-220 to I-222 (T.sup.1=piperidinyl) and I-190, I-203, I-224 to I-225 and I-230 (T.sup.1=pyrrolidinyl).

[1019] The N,N-dialkyl-carbamimidothioic acid methyl ester are either commercially available or may be synthesized by methods known to the skilled artisan.

[1020] For N,N-dimethyl-carbamimidothioic acid methyl ester, see CAS-no: 57618-94-7 (Enamine building blocks).

[1021] For N-ethyl-N-methyl-carbamimidothioic acid methyl ester, see CAS-no: 787521-54-4 (Chemieliva Pharmaceutical Product List).

[1022] For N,N-diethyl-carbamimidothioic acid methyl ester, see CAS-no: 89269-29-4 (Chemieliva Pharmaceutical Product List).

[1023] For N-methyl-N-(1-methylethyl)-carbamimidothioic acid methyl ester, see CAS-no: 1365957-47-6 (FCH Group Reagents for Synthesis).

[1024] For N-methyl-N-propyl-carbamimidothioic acid methyl ester, see CAS-no: 764620-88-4 (Chemieliva Pharmaceutical Product List).

[1025] The N-cycloalkylaminecarboximidothioic acid methyl ester are either commercially available or may be synthesized by methods known to the skilled artisan (e.g. WO 2018/089904 A1).

[1026] For 4-morpholinecarboximidothioic acid methyl ester, see CAS-no: 89269-30-7 (Chemieliva Pharmaceutical Product List).

[1027] For 1-pyrrolidinecarboximidothioic acid methyl ester, see CAS-no: 758658-51-4 (Chemieliva Pharmaceutical Product List).

[1028] For 1-piperidinecarboximidothioic acid methyl ester, the 1-piperidinecarbothioamide (CAS-no: 14294-09-8 (ABCR GmbH Product List) can be used as starting compound for S-methylation by methods known to the skilled artisan.

[1029] Scheme 17 illustrates the preparation 3-(N-alkyl, N-alkoxy)-amino substituted 1,2,4-triazoles (I″v) starting with 3-(N-alkyl, N-alkoxy)-amino-1,2,4-triazole containing amines (jd) as intermediates (see INT-026). R.sup.1 is hydrogen, R.sup.3a is methyl, R.sup.3b is hydrogen, X is oxygen, Y is a direct bond, R.sup.5 is a N(R′)OR group and R.sup.2 as well as R.sup.4 have the meanings given in of formula I.

##STR00065##

[1030] In a first step, N-Boc-alanine (ea) reacts for example with N-alkoxy-N-alkyl-carb-amimidothioic acid methyl ester monohydroiodides (Hal=I) (fd) in the presence of a base and the coupling reagent HATU to form the N-acylated tert-butyl N-[(1S)-2-[[N-alkoxy-N-alkylamino (methylsulfanyl)methylene]amino]-1-methyl-2-oxo-ethyl] carbamates (gd), which can be used without purification. In a second step the cyclization of (gd) occurs with R.sup.4-substituted hydrazines (h) and in the presence of an acid, like acetic acid to form the 1,2,4-triazoles of formula (id), wherein R.sup.5 is a N(R′)OR group. In the third step the N-Boc protection group is removed from the 1,2,4-triazoles of formula (id), wherein R.sup.5 is a N(R′)OR group (see scheme 17), by reaction with 4N HCl in dioxane to form the 3-(N-alkoxy-N-alkyl) containing amines or the related hydrochloride salt (jd) (see INT-026) as demonstrated by the example compounds I-149 to I-153.

[1031] The N-alkoxy-N-alkyl-,carbamimidothioic acid methyl ester may be synthesized by methods known to the skilled artisan.

[1032] For N-methoxy-N-methyl-carbamimidothioic acid methyl ester-monohydroiodide, see CAS-no: 749181-24-6 (WO 9300336 A1).

[1033] For N-ethoxy-N-methyl-carbamimidothioic acid methyl ester-monohydroiodide, see CAS-no: 153068-71-4 (WO 9300336 A1).

[1034] For N-methyl-N-propoxy-carbamimidothioic acid methyl ester-monohydroiodide, see CAS-no: 153068-72-5 (WO 9300336 A1).

[1035] Scheme 18 illustrates the preparation 3-amino-1,2,4-triazoles (I″w) starting with 3-amino-1,2,4-triazole containing amines (jd) (see INT-025

##STR00066##

[1036] In a first step, N-Boc-alanine (ea) reacts with 1-N-Boc-2-methyl-isothiourea (f) (purchased from ABCR) (see scheme 4) in the presence of a base and the coupling reagent HATU to form the tert-butyl N-[(1S)-2-[[(tert-butoxycarbonylamino)-methylsulfanyl-methylene]amino]-1-methyl-2-oxo-ethyl]carbamate (gd), which can be used without purification. In a second step the cyclization of (gd) occurs with R.sup.4-substituted hydrazines (h) and in the presence of an acid, like acetic acid to form the 1,2,4-triazoles of formula (id), wherein R.sup.5 is NH-Boc. In the third step both N-Boc protection groups are removed from the 1,2,4-triazoles of formula (id), wherein R.sup.5 is NH-Boc, by reaction with 4N HCl in dioxane to form the 3-amino-1,2,4-triazole containing amines or the related hydrochloride salt (id) (see INT-025, INT-030, INT-035 and INT-038) as demonstrated by the example compounds I-148, I-154, I-155, I-169, I-172, I-173, I-187 to I-189, I-205, I-211, I-213 to 216, I-241 to I-251 and I-285 to I-286.

[1037] The 1-N-Boc-2-methyl-isothiourea is either commercially available or may be synthesized by methods known to the skilled artisan (see scheme 4).

[1038] Scheme 19 illustrates the preparation of enantiomeric enriched 3-tert-butoxycarbonyl-amino-, 3-tert-butoxycarbonyl-alkylamino-(I″x), (I″xa) as well as 3-alkylamino- and 3-amino-1,2,4-triazoles (I″w), (I″t) by chromatographic separation of the racemic 3-tert-butoxycarbonyl-amino- and 3-tert-butoxycarbonyl-alkylamino-1,2,4-triazoles (I″h) and (I″ha) on a chiral stationary phase (see example I-133 and I-135). R.sup.1 is hydrogen, R.sup.3a is methyl, R.sup.3b is hydrogen, X is oxygen, Y is a direct bond, R.sup.5 is N-Boc-amino, N-Boc-alkylamino or amino, N-alkylamino and R.sup.2 as well as R.sup.4 have the meanings given in of formula I.

##STR00067##

[1039] In a first step, the racemic 3-tert-butoxycarbonyl-amino- and 3-tert-butoxycarbonyl-alkylamino-1,2,4-triazoles (I″h) and (I″ha), prepared as crude materials according to scheme 4 and scheme 5 (e.g. by using the 3-alkylamino-1,2,4-triazole containing amines (ja)), were separated by supercritical fluid chromatography (SFC) on a chiral stationary phase (Chiracel OD-H) into their (R) and (S)-isomers. The substances were isolated from the fractions by evaporation at 40° C. under vacuum and dried at 10 mbar for 10 minutes to afford the enantiomeric enriched (S)-isomers of 3-tert-butoxycarbonyl-amino- and 3-tert-butoxycarbonyl-alkylamino-1,2,4-triazoles (I″x) and (I″xa). In a second step the N-Boc protection groups are removed from the 1,2,4-triazoles of formula (I″x) and (I″xa), wherein R.sup.5 is NH-Boc and NR-Boc by reaction with 4N HCl in dioxane to form the 3-amino-1,2,4-triazoles or the related hydrochloride salt (I″w) and 3-alkylamino-1,2,4-triazoles or the related hydrochloride salt (I″t) as demonstrated by the example compounds (I-127 and I-134).

[1040] Alternatively, the enantiomeric enriched 3-alkylamino-1,2,4-triazole (I″t) and 3-amino-1,2,4-triazoles (I″w) can be prepared by total syntheses according to the schemes 15 and 18.

PREPARATION OF EXAMPLES

Synthesis of tert-butyl N-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate (example I-001)

[1041] ##STR00068##

Step 1

tert-Butyl N—[N-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]carbamate

[1042] ##STR00069##

[1043] To 1.09 g (5.0 mmol) (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (Pht-Ala-OH purchased from ABCR) und 0.95 g (5.0 mmol) 1-N-Boc-2-methyl-isothiourea (purchased from ABCR) in THF (30 ml), triethylamine (2.1 mL) and 2.85 g (7.5 mmol) HATU was added, and the reaction mixture was stirred at 80° C. temperature and stirred further 2 h at the same temperature. Then water was added and the mixture was extracted with NaHCO.sub.3 solution and dichloromethane. After drying the solvent was evaporated. The remaining solid residue was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 1.40 g (purity: 97.0%; yield: 70%) of the racemic title compound.

[1044] Formula: C.sub.18H.sub.21N.sub.3O.sub.5S Molecular weight: 391.44 g/mol

[1045] UPLC-MS (acid) [m/z]: 392.2 [M+H].sup.+

[1046] .sup.1H-NMR peaklist (400 MHz, DMSO-d.sub.6, ppm): δ=11.8958 (0.5); 11.4353 (0.9); 7.9299 (0.5); 7.9221 (1.0); 7.9152 (1.2); 7.9102 (1.0); 7.9063 (1.2); 7.9000 (2.1); 7.8930 (1.1); 7.8847 (2.6); 7.8785 (1.3); 7.8744 (1.2); 7.8627 (0.8); 4.9976 (0.8); 4.9794 (0.8); 3.3230 (9.5); 2.5251 (0.4); 2.5204 (0.6); 2.5117 (8.2); 2.5072 (16.6); 2.5027 (21.9); 2.4981 (15.8); 2.4936 (7.6); 2.2949 (2.4); 1.9720 (6.0); 1.6029 (2.9); 1.5848 (3.0); 1.5719 (1.3); 1.5540 (1.1); 1.4430 (16.0); 1.3971 (11.0); 1.2665 (6.6); −0.0002 (0.5).

Step 2

tert-Butyl N-[5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate

[1047] ##STR00070##

[1048] To a solution of 1.0 g (2.55 mmol) tert-butyl N—[(E)-N-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]carbamate in pyridine (50 ml), 337.5 mg (3.06 mmol) 2-hydrazino-pyrimidine was added and the reaction mixture was stirred at room temperature for 2 h at 80° C. temperature. Afterwards the solvent was evaporated in vacuo the crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 780 mg (purity: 95.9%; yield: 67%) of the racemic title compound.

[1049] Formula: C.sub.21H.sub.21N.sub.7O.sub.4 Molecular weight: 435.43 g/mol

[1050] UPLC-MS (acid) [m/z]: 436.3 [M+H].sup.+

[1051] .sup.1H-NMR peaklist (600 MHz, DMSO-d.sub.6, ppm): δ=9.9739 (1.2); 8.7635 (2.7); 8.7554 (2.7); 7.8169 (0.6); 7.8126 (0.8); 7.8097 (2.9); 7.8052 (3.0); 7.8020 (0.9); 7.7979 (0.6); 7.4395 (0.7); 7.4315 (1.4); 7.4234 (0.7); 6.0850 (0.8); 6.0732 (0.8); 5.7533 (0.3); 3.3088 (9.2); 2.5080 (3.8); 2.5050 (8.0); 2.5020 (11.1); 2.4989 (8.1); 2.4960 (3.8); 1.9448 (0.4); 1.9123 (0.4); 1.8008 (2.4); 1.7890 (2.4); 1.4365 (16.0); 1.3974 (6.1); −0.0001 (1.9).

Step 3

tert-Butyl N-[5-(1-aminoethyl)-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate (INT-001)

[1052] ##STR00071##

[1053] To 900.0 mg (2.06 mmol) tert-butyl N-[5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate in ethanol (50 mL), 470.3 mg (5.16 mmol) hydrazine-hydrate were added, and the reaction mixture was heated under reflux. After 30 minutes a colorless precipitate was formed. The reaction mixture was stirred and heated under reflux two additional hour, acetone (30 mL) was added and the heating was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was treated with ethanol. After filtration, the filtrate was evaporated under reduced pressure to afford the racemic intermediate (INT-001), which was used in step 4 without purification.

[1054] Formula: C.sub.13H.sub.19N.sub.7O.sub.2 Molecular weight: 305.34 g/mol

[1055] HPLC-MS (ESI-positive) [m/z]: 306.2 [M+H].sup.+

[1056] The intermediate of the formulae (INT-002) listed in Table 2 below can be prepared analogously.

Step 4

tert-Butyl N-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate

[1057] To 973.8 mg (2.60 mmol) tert-butyl N-[5-(1-aminoethyl)-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate, 601.9 mg (2.60 mmol) 3-chloro-5-(trifluoromethyl)-benzoic acid, 436.8 mg (3.38 mmol) DIPEA in DMF (10 mL), 1.18 g (3.12 mmol) HATU were added, and the reaction mixture was stirred at room temperature over night. The reaction mixture was concentrated under reduced pressure and the solid residue was treated with dichloromethane and then extracted with a saturated aqueous NaHCO.sub.3 solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 284 mg (purity: 90.0%; yield: 19%) of the racemic title compound.

[1058] Formula: C.sub.21H.sub.21ClFN.sub.7O.sub.3 Molecular weight: 511.89 g/mol

[1059] UPLC-MS neutral: 512.2 [M+H].sup.+

[1060] The compounds of the formulae (I-002)-(I-003) listed in Table 1 below can be prepared analogously.

Synthesis of N-[1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3-chloro-5-(trifluoromethyl)benzamide (example I-004)

[1061] ##STR00072##

[1062] 2.8 g (2.64 mmol) tert-butyl N-[5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate were dissolved in 4N HCl-dioxane solution (50 mL) and the mixture was stirred 18 h at room temperature. Then, the solvent was evaporated under reduced pressure to afford 2.3 g (purity: 94%) of the racemic title compound, which was used for further reaction steps.

[1063] Formula: C.sub.16H.sub.14Cl.sub.2F.sub.3N.sub.7O Molecular weight: 248.23 g/mol

[1064] HPLC-MS neutral (ESI-positive) [m/z]: 412.1 [M−HCl].sup.+

[1065] The compounds of the formulae (I-005)-(I-008) listed in Table 1 below can be prepared analogously.

Synthesis of tert-butyl N-[5-[1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate (example I-009)

[1066] ##STR00073##

Step 1

tert-butyl N-methyl-N-(methylsulfanylcarbonimidoyl)carbamate

[1067] ##STR00074##

[1068] To a mixture of 10.0 g (43.0 mmol) 1,2-dimethylisothiourea hydroiodide, tetrahydrofurane (150 mL), water (150 mL) and NaHCO.sub.3 solution, 10.3 g (47.3 mmol) di-tert-butyl dicarbonate was added, and the reaction mixture was stirred at room temperature overnight. Then water was added and the mixture was extracted with EtOAc. After drying the solvent was evaporated to afford 7.10 g (purity: 71.0%; yield: 81%) of the title compound as yellow oil.

[1069] Formula: C.sub.8H.sub.16N.sub.2O.sub.2S Molecular weight: 204.29 g/mol

[1070] UPLC-MS (neutral) [m/z]: 148.9 [M−H.sub.2C═CMe.sub.2].sup.+

[1071] .sup.1H-NMR peaklist (600 MHz, CD.sub.3CN, ppm): δ=3.2027 (1.0); 3.0846 (0.6); 2.3498 (0.5); 2.2547 (1.4); 2.1637 (8.9); 1.9485 (0.8); 1.9444 (1.4); 1.9403 (2.1); 1.9362 (1.4); 1.9320 (0.7); 1.4932 (2.4); 1.4819 (16.0); 1.4324 (2.0).

Step 2

tert-Butyl N—[N-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]-N-methyl-carbamate

[1072] ##STR00075##

[1073] To 7.60 g (34.6 mmol) (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (Pht-Ala-OH purchased from ABCR) und 7.08 g (34.6 mmol) tert-butyl N-methyl-N-(methylsulfanyl-carbonimidoyl)carbamate in THF (321.8 mL), triethylamin (14.5 ml) and HATU was added, and the reaction mixture was stirred at 80° C. temperature and stirred further 2 h at the same temperature. Then tetrahydrofuran was evaporated and the mixture was extracted with NaHCO.sub.3 solution and dichloromethane. The organic phase was dried and evaporated to afford the racemic title compound as colorless oil.

[1074] Formula: C.sub.19H.sub.23N.sub.3O.sub.5S Molecular weight: 405.47 g/mol

[1075] HPLC-MS neutral (ESI-positive) [m/z]: 406.2 [M+H].sup.+

Step 3

tert-Butyl N-[5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate

[1076] ##STR00076##

[1077] To a solution of 7.5 g (18.4 mmol) tert-butyl N—[(E)-N-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]-N-methyl-carbamate in pyridine (50 ml), 2.5 g (22.7 mmol) 2-hydrazinopyrimidine was added and the reaction mixture was stirred at room temperature for 2 h at 80° C. temperature. Afterwards the solvent was evaporated in vacuo and the crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 6.0 g (purity: 97.5%; yield: 70%) of the racemic title compound.

[1078] Formula: C.sub.22H.sub.23N.sub.7O.sub.4 Molecular weight: 449.47 g/mol

[1079] HPLC-MS acid (ESI-positive) [m/z]: 450.2 [M+H].sup.+

Step 4

tert-Butyl N-[5-(1-aminoethyl)-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate (INT-003)

[1080] ##STR00077##

[1081] To 6.0 g (13.3 mmol) tert-butyl N-[5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate in ethanol (150 mL), 3.06 g (33.7 mmol) hydrazine-hydrate were added, and the reaction mixture was heated under reflux. After 30 minutes a colorless precipitate was formed. The reaction mixture was stirred and heated under reflux two additional hours, acetone (10 mL) was added and the heating was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was treated with ethanol. After filtration, the filtrate was evaporated under reduced pressure to afford the racemic intermediate (INT-003), which was used in step 4 without purification.

[1082] Formula: C.sub.14H.sub.21N.sub.7O.sub.2 Molecular weight: 319.36 g/mol

[1083] HPLC-MS acid (ESI-positive) [m/z]: 320.2 [M+H].sup.+

Step 5

tert-Butyl N-[5-[1-1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate

[1084] To 671.55 mg (2.60 mmol) tert-butyl N-[5-(1-aminoethyl)-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate, 250.0 mg (0.93 mmol) 3,5-bis-(trifluoromethyl)-benzoic acid, 157.8 mg (1.22 mmol) DIPEA in 15.78 g (384.5 mmol) MeCN, 228.67 mg (1.12 mmol) HATU were added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the solid residue was treated with dichloromethane and then extracted with a saturated aqueous NaHCO.sub.3 solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining residue was purified by HPLC with a water/MeCN neutral gradient to obtain 422 mg (purity: 99.0%; yield: 79%) of the racemic title compound.

[1085] Formula: C.sub.23H.sub.23F.sub.6N.sub.7O.sub.3 Molecular weight: 559.47 g/mol

[1086] HPLC-MS acid (ESI-positive): 512.2 [M+H].sup.+

Synthesis of methyl N-[1-(5-chloro-2-pyridyl)-5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1,2,4-triazol-3-yl]carbamate (example I-010)

[1087] ##STR00078##

[1088] To 200.0 mg (0.44 mmol)N-[1-[5-amino-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-(trifluoromethyl)benzamide in THF (15 mL), 77.2 mg (0.76 mmol) triethylamine and 488.1 mg (5.16 mmol) methyl chloroformate was added, and then the reaction mixture was stirred 18 h at room temperature. Because a low conversion was observed, 10 equivalents of methyl chloroformate were added and the reaction mixture was stirred further 18 h at room temperature. After filtration, the filtrate was evaporated under reduced pressure. The remaining residue was purified by HPLC with a water/acetonitrile neutral gradient to obtain 110.5 mg (purity: 100%; yield: 49%) of the racemic title compound.

[1089] Formula: C.sub.19H.sub.15Cl.sub.2F.sub.3N.sub.6O.sub.3 Molecular weight: 503.27 g/mol

[1090] HPLC-MS (ESI-positive): 503.1 [M+H].sup.+

Synthesis of N-[1-[5-acetamido-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-(trifluoromethyl)benzamide (example I-011)

[1091] ##STR00079##

[1092] To 200.0 mg (0.44 mmol)N-[1-[5-amino-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-(trifluoromethyl)benzamide in THF (15 mL), 77.2 mg (0.76 mmol) triethylamine and 52.8 mg (0.67 mmol) acetyl chloride was added, and then the reaction mixture was stirred 18 h at room temperature. After filtration, the filtrate was evaporated under reduced pressure to obtain 166.0 mg (purity: 96.9%; yield: 74%) of the racemic title compound.

[1093] Formula: C.sub.19H.sub.15Cl.sub.2F.sub.3N.sub.6O.sub.2 Molecular weight: 487.27 g/mol

[1094] HPLC-MS (ESI-positive) [m/z]: 487.1 [M+H].sup.+

[1095] The compounds of the formulae (I-012)-(I-024) listed in Table 1 below can be prepared analogously.

Synthesis of N-[5-(1-aminoethyl)-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-1,1-difluoro-methanesulfonamide (intermediate INT-004)

[1096] ##STR00080##

Step 1

1-(difluoromethylsulfonyl)-2-methyl-isothiourea

[1097] ##STR00081##

[1098] To 250.0 mg (1.32 mmol) 2-methylisothiourea sulfuric acid salt in dichloromethane (10 mL) and 250.0 mg (2.35 mmol) Na.sub.2CO.sub.3, 239.9 mg (1.59 mmol) difluoromethane sulfonylchloride was added, and the reaction mixture was stirred at room temperature overnight. Then water was added and the mixture was extracted with dichloromethane. After separation of the layers, the organic layer was dried and the solvent evaporated to afford 158 mg (purity: 78.0%; yield: 58%) of the title compound as yellow oil, which was used for the second step.

[1099] Formula: C.sub.3H.sub.6F.sub.2N.sub.2O.sub.2S.sub.2 Molecular weight: 204.21 g/mol

[1100] HPLC-MS acid (ESI-positive) [m/z]: 205.1 [M+H].sup.+

Step 2

N-[(Difluoromethylsulfonylamino)-methylsulfanyl-methylene]-2-(1,3-dioxoisoindolin-2-yl)propenamide

[1101] ##STR00082##

[1102] To 0.18 g (0.82 mmol) (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (Pht-Ala-OH purchased from ABCR) and 0.15 g (0.77 mmol 1-(difluoromethylsulfonyl)-2-methyl-isothiourea in tetrahydrofuran (3.56 mL), triethylamin (0.34 mL) and 0.46 g (1.23 mmol) HATU was added, and the reaction mixture was stirred at 80° C. temperature and stirred further 2 h at the same temperature. Then tetrahydrofuran was evaporated and the mixture was extracted with sodium hydrogencarbonate solution and dichloromethane. The organic phase was dried and evaporated to afford the racemic title compound, which was used for step 3 without purification.

[1103] Formula: C.sub.14H.sub.13F.sub.2N.sub.3O.sub.5S.sub.2 Molecular weight: 405.40 g/mol

[1104] HPLC-MS neutral (ESI-positive) [m/z]: 406.0 [M+H].sup.+

Step 3

N-[5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-1,1-difluoro-methanesulfonamide

[1105] ##STR00083##

[1106] To a solution of 700 mg (1.72 mmol)N-[(difluoromethylsulfonylamino)-methylsulfanyl-methylene]-2-(1,3-dioxoisoindolin-2-yl)propanamide in pyridine (20 ml), 233.9 mg (2.12 mmol) 2-hydrazinopyrimidine was added and the reaction mixture was stirred at room temperature for 2 h at 80° C. temperature. Afterwards the solvent was evaporated in vacuo and the crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 380.0 mg (purity: 98.0%; yield: 48%) of the racemic title compound (55 mol-%) as pyridine (45 mol %) adduct (according to the .sup.13C with .sup.1H decoupling data, CPD).

[1107] Formula: C.sub.17H.sub.13F.sub.2N.sub.7O.sub.4S Molecular weight: 449.39 g/mol

[1108] HPLC-MS acid (ESI-positive) [m/z]: 450.1 [M+H].sup.+

[1109] .sup.1H-NMR peaklist (600 MHz, DMSO-d.sub.6, ppm): δ=8.7717 (15.4); 8.7636 (15.7); 8.6322 (3.5); 8.6293 (4.8); 8.6268 (2.5); 8.6249 (2.5); 8.6222 (4.8); 8.6195 (3.4); 7.9149 (0.8); 7.9120 (1.6); 7.9090 (0.8); 7.9022 (1.6); 7.8992 (3.2); 7.8963 (1.6); 7.8894 (0.9); 7.8865 (1.7); 7.8835 (0.9); 7.8303 (0.5); 7.8280 (1.0); 7.8273 (1.0); 7.8247 (0.7); 7.8193 (2.2); 7.8127 (15.6); 7.8100 (16.0); 7.8072 (5.5); 7.8035 (2.2); 7.7981 (0.7); 7.7954 (1.0); 7.4922 (4.5); 7.4898 (2.5); 7.4848 (2.6); 7.4824 (4.5); 7.4794 (4.4); 7.4770 (2.3); 7.4721 (2.3); 7.4697 (4.1); 7.4586 (4.2); 7.4505 (8.0); 7.4425 (4.0); 7.1798 (1.7); 7.0913 (3.9); 7.0029 (2.0); 6.0923 (1.1); 6.0806 (4.4); 6.0688 (4.4); 6.0570 (1.1); 3.4408 (0.4); 3.4338 (0.4); 3.4204 (0.4); 3.4101 (0.4); 3.3821 (0.4); 3.3697 (0.3); 3.3237 (0.3); 2.6182 (0.4); 2.6152 (0.5); 2.6121 (0.4); 2.5920 (0.5); 2.5242 (1.2); 2.5211 (1.5); 2.5180 (1.4); 2.5092 (26.6); 2.5061 (56.6); 2.5031 (79.1); 2.5000 (58.5); 2.4971 (27.2); 2.3901 (0.4); 2.3870 (0.5); 2.3840 (0.4); 2.0866 (7.8); 1.9675 (0.5); 1.9345 (0.5); 1.7998 (13.1); 1.7881 (13.1); −0.0001 (4.4).

Step 4

N-[5-(1-Aminoethyl)-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-1,1-difluoro-methanesulfonamide (INT-004)

[1110] ##STR00084##

[1111] To 500 mg (1.11 mmol)N-[5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-1,1-difluoro-methanesulfonamide in ethanol (30 mL), 270 mg (2.96 mmol) hydrazine-hydrate were added, and the reaction mixture was heated under reflux. After 30 minutes a colorless precipitate was formed. The reaction mixture was stirred and heated under reflux two additional hour, acetone (10 mL) was added and the heating was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was treated with ethanol. After filtration, the filtrate was evaporated under reduced pressure to afford the racemic intermediate (INT-004), which can be used without purification.

[1112] Formula: C.sub.9H.sub.11F.sub.2N.sub.7O.sub.2S Molecular weight: 319.29 g/mol

[1113] HPLC-MS acid (ESI-positive) [m/z]: 320.0 [M+H].sup.+

Synthesis of 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-(methanesulfonamido)-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide (example I-025)

[1114] ##STR00085##

[1115] To 200.0 mg (0.43 mmol)N-[1-[5-amino-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-methylsulfonyl-benzamidein THF (15 mL), 53.3 mg (0.52 mmol) triethylamine and 55.3 mg (0.48 mmol) methylsulfonyl chloride was added, and then the reaction mixture was stirred 18 h at room temperature. Afterwards the solvent was evaporated in vacuo and the crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to obtain 50.0 mg (purity: 95.9%; yield: 20.4%) of the racemic title compound and 50.9 mg (purity: 98.6%; yield: 19%) of N-[1-[5-[bis(methylsulfonyl)amino]-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-methylsulfonyl-benzamide as racemic side product.

[1116] Formula: C.sub.18H.sub.18Cl.sub.2N.sub.6O.sub.5S.sub.2 Molecular weight: 533.41 g/mol

[1117] HPLC-MS (ESI-positive) [m/z]: 533.1 [M+H].sup.+

Synthesis of N-[1-[5-[bis(methylsulfonyl)amino]-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-methylsulfonyl-benzamide (example I-026)

[1118] ##STR00086##

[1119] Formula: C.sub.19H.sub.20Cl.sub.2N.sub.6O.sub.7S.sub.3 Molecular weight: 611.49 g/mol

[1120] HPLC-MS (ESI-positive) [m/z]: 611.1 [M+H].sup.+

Synthesis of 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-(methylsulfonylmethyl)-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide (example I-027)

[1121] ##STR00087##

Step 1

N′-[(5-chloro-2-pyridyl)amino]-2-methylsulfonyl-acetamidine

[1122] ##STR00088##

[1123] To 4.0 g (27.8 mmol) 5-chloro-2-hydrazino-pyridine in 37.2 g (471.0 mmol) pyridine, 2-(methyl-sulfonyl)-ethanimidic acid ethyl ester hydrochloride (1:1) (W. Tang, et al., J. Amer. Chem. Soc. 137(18), 5980-5989, 2015) was added, and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the residue was then stirred with MeOH. The precipitate was separated and dried to obtain 7.3 g (purity: 100%; yield: 99%)N-[(5-Chloro-2-pyridyl)amino]-2-methylsulfonyl-acetamidine.

[1124] Formula: C.sub.8H.sub.11ClN.sub.4O.sub.2S Molecular weight: 262.71 g/mol

[1125] HPLC-MS (ESI-positive) [m/z]: 263.0 [M+H].sup.+

Step 2

2-[1-[2-(5-chloro-2-pyridyl)-5-(methylsulfonylmethyl)-1,2,4-triazol-3-yl]ethyl]isoindoline-1,3-dione

[1126] ##STR00089##

[1127] To 7.30 g (27.78 mmol) N′-[(5-chloro-2-pyridyl)amino]-2-methylsulfonyl-acetamidine in pyridine (300 mL), 5.42 g (22.80 mmol) (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetyl chloride (see preparation from (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (Pht-Ala-OH purchased from ABCR) and oxalyl chloride: D. A. Gruzdev et al., Tetrahedron: Asymmetry, 21(8), 936-942, 2010) was added, and the reaction mixture was stirred at room temperature overnight. Then water and dichloromethane was added and the mixture was treated with NaHCO.sub.3 solution. The organic phase was separated, dried and the solvent was evaporated. The remaining residue was treated with DMF filtered and purified by HPLC with a acetonitrile/water gradient (acid) to afford 1.01 g (purity: 94%; yield: 9%) of the racemic title compound and 2.20 g (purity: 83.0%; yield: 12%)N-[6-chloro-2-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-3-(methylsulfonylmethyl)-[1,2,4]triazolo [4,3-a]pyridin-3-yl]-2-(1,3-dioxoisoindolin-2-yl)propenamide as side product.

[1128] Formula: C.sub.19H.sub.16ClN.sub.5O.sub.4S Molecular weight: 445.88 g/mol

[1129] HPLC-MS neutral (ESI positive) [m/z]: 446.1 [M+H].sup.+

[1130] .sup.1H-NMR (600.1 MHz, CD.sub.3CN, ppm): δ=8.2135 (1.8); 8.2093 (1.9); 7.8432 (1.4); 7.8389 (1.4); 7.8287 (1.8); 7.8244 (1.8); 7.7437 (16.0); 7.7061 (2.4); 7.6916 (2.0); 6.0901 (0.5); 6.0783 (1.8); 6.0666 (1.9); 6.0548 (0.6); 4.4882 (5.9); 4.0787 (0.4); 3.0993 (11.5); 3.0514 (0.3); 3.0427 (0.7); 2.1342 (13.9); 2.0862 (1.8); 1.9640 (1.7); 1.9559 (0.9); 1.9518 (1.0); 1.9479 (6.5); 1.9439 (11.4); 1.9397 (16.7); 1.9356 (11.4); 1.9315 (5.8); 1.8544 (7.4); 1.8426 (7.4); 1.6343 (0.5); 1.6222 (0.5); 1.4364 (8.2); −0.0001 (0.5).

Step 3

1-[2-(5-Chloro-2-pyridyl)-5-(methylsulfonylmethyl)-1,2,4-triazol-3-yl]ethanamine (INT-005)

[1131] ##STR00090##

[1132] To 1.0 g (2.24 mmol) 2-[1-[2-(5-chloro-2-pyridyl)-5-(methylsulfonylmethyl)-1,2,4-triazol-3-yl]ethyl]isoindoline-1,3-dione in ethanol (25 mL), 510.3 mg (5.60 mmol) hydrazine-hydrate was added, and the reaction mixture was heated under reflux. The reaction mixture was stirred and heated under reflux for 2 h, acetone (25 mL) was added and the heating was continued for further 1 h. The reaction mixture was concentrated and the solid residue was treated with ethanol (100 mL). Then, the solvent was evaporated and the crystals were separated to afford 1.0 g of the racemic intermediate (INT-005), which was used for the N-acylation reaction (step 4) without purification.

[1133] Formula: C.sub.11H.sub.14ClN.sub.5O.sub.2S Molecular weight: 315.78 g/mol

Step 4

3-Chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-(methylsulfonylmethyl)-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide

[1134] To 254.6 mg (0.80 mmol) 1-[2-(5-chloro-2-pyridyl)-5-(methylsulfonylmethyl)-1,2,4-triazol-3-yl]ethanamine (INT-005), 270.2 mg (1.15 mmol) 3-chloro-5-(methylsulfonyl)-benzoic acid, 744.3 mg (5.75 mmol) DIPEA in DMF (6.9 mL), 525.5 mg (1.38 mmol) HATU was added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture filtered, concentrated and the residue was purified by HPLC with a acetonitrile/water gradient (acid) to afford 251.5 mg (purity: 95.2%; yield: 39%) of the title compound.

[1135] Formula: C.sub.19H.sub.19Cl.sub.2N.sub.5O.sub.5S.sub.2 Molecular weight: 532.42 g/mol

[1136] HPLC-MS acid (ESI positive): 532.0 [M+H].sup.+

[1137] The compounds of the formulae (I-028)-(I-030) listed in Table 1 below can be prepared analogously.

Synthesis of 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-(6-chloro-3-pyridyl)-1,2,4-triazol-3-yl]ethyl]-5-(trifluoromethoxy)benzamide (example I-031)

[1138] ##STR00091##

Step 1

6-chloro-N′-[(5-chloro-2-pyridyl)amino]pyridine-3-carboxamidine

[1139] ##STR00092##

[1140] To 1.00 g (6.96 mmol) 5-chloro-2-hydrazino-pyridine in methanol (6.9 mL) 2.17 (9.75 mmol) 3-6-chloro-pyridinecarboximidic acid methyl ester (CAS-no. 154753-15-8; e.g. commercial available: Chemieliva Pharmaceutical Product List) was added, and the reaction mixture was stirred at room temperature overnight. The formed precipitate was separated and the residue was then stirred with methanol. The precipitate was separated and dried to obtain 1.64 g (purity: 100%; yield: 83%) 6-chloro-N′-[(5-chloro-2-pyridyl)amino]pyridine-3-carboxamidine, which was used for step 2.

[1141] Formula: C.sub.11H.sub.9Cl.sub.2N.sub.5 Molecular weight: 282.13 g/mol

[1142] HPLC-MS acid (ESI positive): 282.3 [M+H]

Step 2

2-[1-[2-(5-Chloro-2-pyridyl)-5-(6-chloro-3-pyridyl)-1,2,4-triazol-3-yl]ethyl]isoindoline-1,3-dione

[1143] ##STR00093##

[1144] To 1.84 g (5.82 mmol) 6-chloro-N′-[(5-chloro-2-pyridyl)amino]pyridine-3-carboxamidine in pyridine (22 mL), 1.38 g (5.82 mmol) (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetyl chloride (see preparation from (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (Pht-Ala-OH purchased from ABCR) and oxalyl chloride: D. A. Gruzdev et al., Tetrahedron: Asymmetry, 21(8), 936-942, 2010) was added, and the reaction mixture was stirred at room temperature overnight. Then water and dichloromethane was added and the mixture was treated with NaHCO.sub.3 solution. The organic phase was separated, dried and the solvent was evaporated. The remaining residue was treated with DMF filtered and purified by HPLC with a MeCN/water gradient (acid) to afford 350.0 mg (purity: 100%; yield: 13%) of the racemic title compound and 791.0 g (purity: 99.0%; yield: 2%)N-[6-chloro-3-(6-chloro-3-pyridyl)-2-[2-(1,3-dioxoisoindolin-2-yl)propanoyl]-[1,2,4]triazolo[4,3-a]pyridin-3-yl]-2-(1,3-dioxoisoindolin-2-yl)propenamide as side product.

[1145] Formula: C.sub.22H.sub.14Cl.sub.2N.sub.6O.sub.2 Molecular weight: 465.30 g/mol

[1146] HPLC-MS (ESI positive) [m/z]: 465.1 [M+H].sup.+

[1147] .sup.1H-NMR peaklist (600 MHz, d.sub.6-DMSO, ppm): δ=9.0704 (6.3); 9.0666 (6.1); 8.4602 (4.0); 8.4562 (3.9); 8.4464 (4.1); 8.4423 (4.0); 8.3054 (6.4); 8.3012 (6.4); 8.1116 (3.8); 8.1073 (3.6); 8.0971 (4.4); 8.0929 (4.2); 7.8968 (7.0); 7.8824 (6.2); 7.8371 (3.4); 7.8310 (4.4); 7.8292 (4.3); 7.8265 (5.1); 7.8224 (11.6); 7.8169 (5.9); 7.8120 (11.8); 7.8080 (5.2); 7.8056 (4.3); 7.8038 (4.3); 7.7976 (3.4); 7.7111 (6.4); 7.6972 (6.2); 6.1120 (1.3); 6.1004 (4.8); 6.0887 (4.9); 6.0769 (1.3); 3.3157 (95.8); 2.6199 (0.7); 2.5288 (1.6); 2.5259 (1.9); 2.5227 (2.1); 2.5107 (90.8); 2.5079 (119.6); 2.5051 (91.5); 2.3919 (0.7); 1.8947 (15.9); 1.8830 (16.0); 0.0054 (4.3).

Step 3

1-[2-(5-Chloro-2-pyridyl)-5-(6-chloro-3-pyridyl)-1,2,4-triazol-3-yl]ethanamine (INT-006)

[1148] ##STR00094##

[1149] To 1.67 g (3.58 mmol) 2-[1-[2-(5-chloro-2-pyridyl)-5-(6-chloro-3-pyridyl)-1,2,4-triazol-3-yl]ethyl]isoindoline-1,3-dione in ethanol (150 mL), 816.7 mg (8.97 mmol) hydrazine-hydrate was added, and the reaction mixture was heated under reflux. The reaction mixture was stirred and heated under reflux for 2 h, acetone (25 mL) was added and the heating was continued for further 1 h. The reaction mixture was concentrated and the solid residue was treated with ethanol (100 mL). Then, the solvent was evaporated and the crystals were separated to afford 710.3 g (yield: 59%) racemic 1-[2-(5-chloro-2-pyridyl)-5-(6-chloro-3-pyridyl)-1,2,4-triazol-3-yl]ethanamine, which was used for the N-acylation reaction (step 4) without purification.

[1150] Formula: C.sub.14H.sub.12Cl.sub.2N.sub.6 Molecular weight: 335.19 g/mol

[1151] HPLC-MS acid (ESI positive): 335.1 [M+H].sup.+

[1152] The intermediates of the formulae (INT-007)-(INT-011) listed in Table 2 below can be prepared analogously.

Step 4

3-Chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-(6-chloro-3-pyridyl)-1,2,4-triazol-3-yl]ethyl]-5-(trifluoromethoxy)benzamide

[1153] To 222.9 mg (0.66 mmol) 1-[2-(5-chloro-2-pyridyl)-5-(6-chloro-3-pyridyl)-1,2,4-triazol-3-yl]ethanamine (INT-006), 235.6 mg (0.95 mmol) 3-chloro-5-(trifluoromethoxy)-benzoic acid, 614.0 mg (4.75 mmol) DIPEA in DMF (6.5 mL), 433.5 mg (1.14 mmol) HATU was added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered, concentrated and the residue was purified by HPLC with a MeCN/water gradient (acid) to afford 103.6 mg (purity: 100%; yield: 16%) of the title compound. The enantiomeric excess of the (S)-enantiomer has been determined via screen OD_RH (acid): ee-value=90%; R.sub.t=16.54 min.

[1154] Formula: C.sub.22H.sub.14Cl.sub.3F.sub.3N.sub.6O.sub.2 Molecular weight: 557.75 g/mol

[1155] HPLC-MS acid (ESI positive): 557.1 [M+H].sup.+

[1156] The compounds of formulae (I-032)-(I-058) listed in Table 1 below can be prepared analogously.

Synthesis of 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-methylsulfanyl-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide (example I-059)

[1157] ##STR00095##

Step 1

(2S)-2-(1,3-dioxoisoindolin-2-yl)propanoyl isothiocyanate

[1158] ##STR00096##

[1159] To 5.42 g (22.80 mmol) (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetyl chloride (see preparation from (αS)-1,3-dihydro-α-methyl-1,3-dioxo-2H-isoindole-2-acetic acid (Pht-Ala-OH purchased from ABCR) and oxalyl chloride: D. A. Gruzdev et al., Tetrahedron: Asymmetry, 21(8), 936-942, 2010) in acetonitrile (210 mL) 1.73 g (22.80 mmol) ammonium thiocyanate was added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered and used for step 2 without isolation.

Step 2

2-[1-[2-(5-Chloro-2-pyridyl)-5-thioxo-1H-1,2,4-triazol-3-yl]ethyl]isoindoline-1,3-dione

[1160] ##STR00097##

[1161] To 2.96 g (11.40 mmol) (2S)-2-(1,3-dioxoisoindolin-2-yl)propanoyl isothiocyanate in acetonitrile (100 mL) 1.63 g (11.40 mmol) 5-chloro-2-hydrazino-pyridine was added, and the reaction mixture was stirred 3 h under reflux temperature. Then, the reaction mixture was concentrated and used for the S-methylation step without purification.

Step 3

2-1-[1-[2-(5-chloro-2-pyridyl)-5-methylsulfanyl-1,2,4-triazol-3-yl]ethyl]isoindoline-1,3-dione

[1162] ##STR00098##

[1163] To 1.40 g (3.62 mmol) 2-[1-[2-(5-chloro-2-pyridyl)-5-thioxo-1H-1,2,4-triazol-3-yl]ethyl]isoindoline-1,3-dione in DMF (30 mL) 152.38 g (3.81 mmol) sodium hydride (purity: 60%) was added, and the reaction mixture was stirred 10 minutes at room temperature. Afterwards 772.52 g (5.44 mmol) iodomethane was added, and the reaction mixture was stirred 3 h at room temperature. Then, the reaction mixture was treated with water (0.5 mL) and stirred further 30 minutes at room temperature. The reaction mixture was evaporated and the remaining residue was chromatographed with a cyclohexane/acetone gradient on silica gel later on and purified by HPLC with a acetonitrile/water gradient (acid) to afford 150.0 mg (purity: 100%; yield: 10%) of the racemic title compound.

[1164] Formula: C.sub.18H.sub.14ClN.sub.5O.sub.2S Molecular weight: 399.86 g/mol

[1165] HPLC-MS acid (ESI positive) [m/z]: 400.1 [M+H].sup.+

[1166] .sup.1H-NMR peaklist (600 MHz, DMSO-d.sub.6, ppm): δ=8.2732 (1.8); 8.2722 (1.8); 8.2689 (1.9); 8.2679 (1.8); 8.0535 (1.6); 8.0491 (1.5); 8.0389 (1.8); 8.0346 (1.7); 7.8289 (1.0); 7.8245 (0.8); 7.8223 (1.2); 7.8212 (1.1); 7.8180 (1.5); 7.8139 (3.8); 7.8069 (4.0); 7.8027 (1.8); 7.7996 (1.1); 7.7986 (1.1); 7.7963 (0.7); 7.7919 (1.1); 7.7566 (2.1); 7.7556 (2.0); 7.7421 (2.0); 7.7411 (1.9); 6.0350 (0.4); 6.0233 (1.7); 6.0115 (1.8); 5.9997 (0.4); 3.3068 (47.6); 2.6130 (0.3); 2.5954 (16.0); 2.5221 (0.6); 2.5190 (0.8); 2.5158 (0.9); 2.5072 (17.2); 2.5041 (36.0); 2.5010 (49.3); 2.4979 (35.4); 2.4949 (16.1); 2.0727 (0.4); 1.7901 (5.1); 1.7784 (5.2); −0.0001 (1.0).

Step 4

1-[2-(5-Chloro-2-pyridyl)-5-methylsulfanyl-1,2,4-triazol-3-yl]ethanamine (INT-012)

[1167] ##STR00099##

[1168] To 880.0 mg (2.22 mmol) 2-[1-[2-(5-chloro-2-pyridyl)-5-methylsulfanyl-1,2,4-triazol-3-yl]ethyl]isoindoline-1,3-dione in ethanol (20.4 mL), 505.3 mg (5.55 mmol) hydrazine-hydrate was added, and the reaction mixture was heated under reflux. The reaction mixture was stirred and heated under reflux for 2 h. Then acetone (25 mL) was added and the heating was continued for further 1 h. The reaction mixture was concentrated and the solid residue was separated to afford 599 mg of the racemic intermediate (INT-012), which was used for the N-acylation reaction (step 5) without purification.

[1169] Formula: C.sub.10H.sub.12ClN.sub.5S Molecular weight: 269.75 g/mol

[1170] HPLC-MS acid (ESI positive): 270.1 [M+H].sup.+

[1171] The intermediates of the formulae (INT-013)-(INT-014) listed in Table 2 below can be prepared analogously.

Step 5

3-Chloro-N-[(1S)-1-[2-(5-chloro-2-pyridyl)-5-methylsulfanyl-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide

[1172] To 603.5 mg (2.23 mmol) 1-[2-(5-chloro-2-pyridyl)-5-methylsulfanyl-1,2,4-triazol-3-yl]ethanamine (INT-012), 750.0 mg (3.19 mmol) 3-chloro-5-(methylsulfonyl)-benzoic acid, 2.06 g (15.98 mmol) DIPEA in DMF (13.3 mL), 1.45 g (3.83 mmol) HATU was added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered, concentrated and the residue was purified by HPLC with a MeCN/water gradient (acid) to afford 830.0 mg (purity: 100%; yield: 53%) of the racemic title compound.

[1173] Formula: C.sub.18H.sub.17Cl.sub.2N.sub.5O.sub.3S.sub.2 Molecular weight: 486.40 g/mol

[1174] HPLC-MS acid (ESI positive): 486.1 [M+H].sup.+

Synthesis of 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-methylsulfonyl-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide (example I-060)

[1175] ##STR00100##

[1176] To 200.0 mg (0.41 mmol) 3-chloro-N-[(1S)-1-[2-(5-chloro-2-pyridyl)-5-methylsulfanyl-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide in dichloromethane (25 mL) 202.7 mg (0.82 mmol) meta-chlorobenzoic acid (mCPBA, 70%) was added, and the reaction mixture was stirred overnight. Then, the reaction mixture was quenched with Na.sub.2CO.sub.3 solution and concentrated. The residue was purified by HPLC with an MeCN/water gradient (acid) to afford 161.3 mg (purity: 100%; yield: 76%) of the racemic title compound and 10.7 mg (purity: 81%, yield: 4%) racemic 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-methylsulfinyl-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide (example I-061) as second compound.

[1177] Formula: C.sub.11H.sub.17Cl.sub.2N.sub.5O.sub.4S.sub.2 Molecular weight: 518.40 g/mol

[1178] HPLC-MS acid (ESI positive): 518.1 [M+H].sup.+

Synthesis of 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-methylsulfinyl-1,2,4-triazol-3-yl]ethyl]-5-methylsulfonyl-benzamide (example I-061)

[1179] ##STR00101##

[1180] Formula: C.sub.18H.sub.17Cl.sub.2N.sub.5O.sub.3S.sub.2 Molecular weight: 502.39 g/mol

[1181] HPLC-MS acid (ESI positive): 502.0 [M+H].sup.+

[1182] The compounds of the formulae (I-062)-(I-070) listed in Table 1 below can be prepared analogously.

Synthesis of 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-cyano-1,2,4-triazol-3-yl]ethyl]-5-(trifluoromethyl)benzamide (example I-071)

[1183] ##STR00102##

Step 1

N-[1-[5-Bromo-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-(trifluoromethyl)benzamide

[1184] ##STR00103##

[1185] To 200.0 mg (0.44 mmol) racemic N-[1-[5-amino-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-(trifluoromethyl)benzamide (1-006) (synthesized according to 1-004) in MeCN (10 mL), 170.5 mg (0.76 mmol) Cu(II)-bromide was added, and then the reaction mixture was treated drop by drop at room temperature with 64.8 mg (0.62 mmol) tert-butyl nitrite. Then the reaction mixture was stirred 1 h at 70° C. temperature. The reaction mixture was treated with acetic acid ethyl ester and then extracted with a saturated NaCl solution. Afterwards the solvent was evaporated in vacuo and the crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 93.8 mg (purity: 99.3%; yield: 41%) of the racemic title compound.

[1186] Formula: C.sub.17H.sub.11BrCl.sub.2F.sub.3N.sub.5O Molecular weight: 509.12 g/mol

[1187] HPLC-MS acid (ESI positive) [m/z]: 510.0 [M+H].sup.+

[1188] .sup.1H-NMR peaklist (600.1 MHz, DMSO-d.sub.6): δ=9.4115 (2.6); 9.4001 (2.7); 8.6396 (0.4); 8.6349 (4.7); 8.6311 (4.5); 8.6307 (4.4); 8.2163 (3.4); 8.2120 (3.3); 8.2089 (0.4); 8.2018 (3.6); 8.1975 (3.6); 8.1214 (4.6); 8.0745 (4.3); 8.0615 (4.7); 7.8651 (5.0); 7.8506 (4.6); 5.9417 (0.4); 5.9302 (2.0); 5.9253 (0.4); 5.9186 (3.2); 5.9139 (0.5); 5.9071 (2.1); 5.8955 (0.4); 3.3216 (92.2); 2.6184 (0.4); 2.6154 (0.5); 2.6124 (0.4); 2.5244 (1.1); 2.5214 (1.4); 2.5182 (1.5); 2.5094 (26.3); 2.5064 (55.2); 2.5033 (76.9); 2.5003 (57.3); 2.4973 (27.2); 2.3904 (0.4); 2.3873 (0.5); 2.3843 (0.3); 1.6353 (11.1); 1.6285 (2.0); 1.6237 (11.1); 1.3974 (16.0); −0.0001 (2.7).

Step 2

Synthesis of 3-chloro-N-[1-[2-(5-chloro-2-pyridyl)-5-cyano-1,2,4-triazol-3-yl]ethyl]-5-(trifluoromethyl)benzamide

[1189] To 500.0 mg (0.98 mmol) racemic N-[1-[5-bromo-2-(5-chloro-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-(trifluoromethyl)benzamide in DMF (20 mL), 567.45 mg (0.49 mmol) tetrakis(triphenylphosphine)palladium(0) and 1.15 g (9.82 mmol) zinc cyanide were added, and the reaction mixture was stirred 8 h at 95° C. under argon atmosphere. The reaction mixture was filtered, concentrated and the residue was purified by HPLC with a MeCN/water gradient (acid) to afford 216.8 mg (purity: 100%; yield: 48%) of the racemic title compound.

[1190] Formula: C.sub.18H.sub.11Cl.sub.2F.sub.3N.sub.6O Molecular weight: 455.22 g/mol

[1191] HPLC-MS acid (ESI positive) [m/z]: 455.1 [M+H].sup.+

Synthesis of 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxylic acid (example I-072)

[1192] ##STR00104##

Step 1

(2S)-2-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]propanoic acid

[1193] ##STR00105##

[1194] A mixture of 22.0 g (246.9 mmol) L-alanine and 39.5 g (987.6 mmol) NaOH in a mixture of water (270 mL) and MeCN (90 mL) was stirred for 20 min at 0° C. To the above mixture was added (60.0 g, 246.9 mmol) 3-chloro-5-(trifluoromethyl)benzoyl chloride which was dissolved in MeCN (30 mL) dropwise over 30 min at 0° C. The resulting mixture was stirred for additional 1 h at room temperature. Then, the mixture was concentrated under reduced pressure. The mixture was acidified to pH 6 with HCl (aq.). The aqueous layer was extracted with EtOAc (3×200 mL). The combined organic layers were washed by brine (100 mL), dried by Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by reverse flash chromatography (C.sub.18 silica gel column; mobile phase, methanol in water, 10% to 50% gradient in 10 min, detector, UV 254 nm) to afford 35.0 g (yield: 48%) of the title compound.

Step 2

methyl 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxylate

[1195] ##STR00106##

[1196] To a stirred mixture of 10.0 g (33.8 mmol) (2S)-2-[[3-chloro-5-(trifluoromethyl)benzoyl] amino]propanoic acid and 19.3 g (50.7 mmol) HATU in DMF (300 mL) were added 4.7 g (33.8 mmol) methyl 2-amino-2-imino-acetate hydrochloride and 13.1 g (101.5 mmol) DIPEA in portions at room temperature. The resulting mixture was stirred for 3 h at room temperature. To the above mixture was added (698.1 mmol) AcOH (40 mL) and 4.5 g (40.6 mmol) 2-hydrazinylpyrimidine in portions within 1 minute at room temperature. The resulting mixture was stirred for additional 1 h at 80° C. The aqueous layer was extracted with ethyl acetate (500 mL). The organic layer was washed by brine (100 mL), dried by Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by reverse flash chromatography (C.sub.18 silica gel column; mobile phase, methanol in water, 10% to 50% gradient in 10 min; detector, UV 254 nm) to afford 4.9 g (32%) of the racemic title compound (partial racemization) as a white solid; 900 mg of which were purified by chiral HPLC chromatography to afford 127.6 mg (yield: 14%) methyl 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxylate as a white solid (major enantiomer) and 104.7 mg (yield: 12%) (minor enantiomer) as a white solid.

[1197] .sup.1H-NMR peaklist (300 MHz, DMSO-d.sub.6, ppm)—major enantiomer: δ=9.5192 (1.3); 9.4959 (1.3); 9.0451 (8.1); 9.0288 (8.3); 8.1212 (2.4); 8.1165 (1.8); 8.0722 (4.7); 8.0691 (4.5); 7.7265 (2.2); 7.7102 (4.0); 7.6940 (2.1); 6.0320 (1.0); 6.0087 (1.5); 5.9855 (1.0); 3.8958 (16.0); 3.3280 (17.2); 2.5158 (5.6); 2.5098 (10.8); 2.5038 (14.1); 2.4978 (9.6); 2.4919 (4.3); 1.6917 (5.2); 1.6685 (5.1); −0.0004 (7.6).

Step 3

5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxylic acid

[1198] To a stirred mixture of 2.5 g (5.5 mmol) racemic methyl 5-[1-[[3-chloro-5-(trifluoromethyl) phenyl]formamido]ethyl]-1-(pyrimidin-2-yl)-1,2,4-triazole-3-carboxylate (from step 2) in a mixture of MeOH (60 mL) and water (20 mL), 0.66 g (16.5 mmol) NaOH was added in portions at room temperature. The resulting mixture was stirred for 30 min at room temperature. Then, the mixture was acidified to pH 5 with HCl (aq.). The resulting mixture was concentrated under reduced pressure. The aqueous layer was extracted with ethyl acetate (3×40 mL). The combined organic layers were washed by brine (100 mL), dried by Na.sub.2SO.sub.4 and concentrated under reduced pressure to get 1.6 g (66%) of the racemic title compound as a white solid.

[1199] .sup.1H-NMR peaklist (300 MHz, DMSO-d.sub.6, ppm): δ=9.4845 (2.0); 9.4608 (2.0); 9.0248 (15.6); 9.0085 (16.0); 8.1180 (5.2); 8.0638 (11.0); 7.6967 (3.8); 7.6804 (7.1); 7.6642 (3.6); 6.0407 (0.4); 6.0177 (1.7); 5.9942 (2.8); 5.9807 (1.0); 5.9707 (1.8); 5.9483 (0.3); 3.3143 (95.7); 2.7332 (1.0); 2.7270 (1.3); 2.7206 (0.8); 2.5130 (83.9); 2.5070 (162.9); 2.5009 (215.8); 2.4949 (146.0); 2.4890 (66.0); 2.2770 (0.9); 2.2708 (1.2); 2.2646 (0.9); 1.9088 (0.4); 1.6790 (10.6); 1.6558 (10.4); 1.2349 (1.9); 1.1662 (0.4); 1.1466 (0.4); 0.4842 (0.7); 0.0106 (1.0); −0.0003 (28.4); −0.0114 (0.9).

Synthesis of 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-(5-cyano-2-pyridyl)-1,2,4-triazole-3-carboxylic acid (example I-073)

[1200] ##STR00107##

Step 1

methyl 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-(5-cyano-2-pyridyl)-1,2,4-triazole-3-carboxylate

[1201] ##STR00108##

[1202] The preparation was carried out analogously to the reaction instructions of example 1-071 (step 2), using:

16.0 g (54.2 mmol) (2S)-2-[[3-chloro-5-(trifluoromethyl)benzoyl] amino]propanoic acid
30.9 g (81.4 mmol) HATU

DMF (320 mL)

[1203] 7.5 g (54.2 mmol) methyl carbamimidoylformate hydrochloride
16.4 g (162.7 mmol) DIPEA
acetic acid (60 mL)
8.7 g (65.1 mmol) 5-cyano-2-hydrazinylpyrimidine

[1204] The residue was purified chiral HPLC chromatography to afford 128.6 mg (yield: 2%) methyl 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-(5-cyano-2-pyridyl)-1,2,4-triazole-3-carboxylate as major enantiomer and 102.2 mg (yield: 2%) as minor enantiomer.

[1205] .sup.1H-NMR peaklist (300 MHz, DMSO-d.sub.6, ppm)—major enantiomer: δ=9.5483 (1.6); 9.5255 (1.6); 9.1190 (2.7); 9.1169 (2.9); 9.1119 (3.0); 9.1098 (2.7); 8.6426 (2.0); 8.6353 (1.9); 8.6141 (2.2); 8.6067 (2.2); 8.1648 (2.9); 8.1377 (2.9); 8.1358 (2.9); 8.1094 (5.2); 8.0749 (2.7); 6.1075 (1.1); 6.0845 (1.7); 6.0614 (1.1); 3.9100 (16.0); 3.3373 (4.2); 2.5265 (2.2); 2.5207 (4.1); 2.5148 (5.4); 2.5090 (3.7); 2.0872 (3.5); 1.6946 (5.8); 1.6714 (5.7); 1.3273 (0.3); −0.0004 (0.7).

Step 2

5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-(5-cyano-2-pyridyl)-1,2,4-triazole-3-carboxylic acid

[1206] To a stirred mixture of 2.0 g (4.2 mmol) racemic methyl 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]-amino]ethyl]-1-(5-cyano-2-pyridyl)-1,2,4-triazole-3-carboxylate in toluene (60 mL) was added 1.5 g (8.4 mmol) Sn(CH.sub.3).sub.3OH in portions at 60° C. The resulting mixture was stirred for 5 h at 60° C. The precipitated solids were collected by filtration and washed with toluene (2×10 mL). The organic layer was concentrated under reduced pressure to afford 1.7 g (yield: 88%) of the racemic title compounds as a white solid.

[1207] .sup.1H-NMR peaklist (300 MHz, DMSO-d.sub.6, ppm): δ=9.5082 (4.2); 9.4854 (4.2); 9.0893 (8.4); 9.0842 (8.6); 8.6227 (6.5); 8.6154 (6.1); 8.5942 (7.1); 8.5868 (7.0); 8.1587 (7.8); 8.1021 (15.7); 8.0737 (15.5); 6.1150 (0.7); 6.0911 (2.6); 6.0681 (4.0); 6.0452 (2.6); 6.0221 (0.7); 3.8979 (0.4); 3.3145 (128.3); 2.7330 (1.4); 2.7272 (1.9); 2.7208 (1.4); 2.6550 (0.4); 2.5131 (120.7); 2.5071 (236.4); 2.5011 (314.8); 2.4951 (213.4); 2.4891 (96.6); 2.2770 (1.3); 2.2711 (1.9); 2.2648 (1.3); 1.9091 (0.5); 1.6742 (16.0); 1.6512 (15.8); 1.2348 (1.4); 1.1578 (0.6); 1.1471 (0.5); 1.1334 (0.4); 0.8550 (0.3); 0.8300 (0.4); 0.0107 (1.6); −0.0003 (43.6); −0.0113 (1.2)

Synthesis of 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxamide (example I-074)

[1208] ##STR00109##

[1209] To a stirred mixture of 1.5 g (3.4 mmol) racemic 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino] ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxylic acid and 1.9 g (5.1 mmol) HATU in DMF (40 mL) were added 0.55 g (10.2 mmol) ammonium chloride and 1.3 g (10.2 mmol) DIEA in portions at room temperature. The resulting mixture was stirred for 1.5 h at room temperature. The residue was dissolved in water (200 mL). The resulting mixture was extracted with ethylacetate (2×60 mL). The combined organic layers were washed with water (3×20 mL), dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reverse flash chromatography (C.sub.18 silica gel column; mobile phase, MeOH in water, 10% to 50% gradient in 10 min; detector, UV 254 nm) to afford 1.0 g (66.8%) racemic 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl] amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxamide as a white solid; 400 mg of which was purified by chiral HPLC column to afford 116.6 mg (29%) 5-[1-[[3-chloro-5-(trifluoromethyl) benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxamide as a white solid (major enantiomer) and 66.4 mg (17%) as a white solid (minor enantiomer).

[1210] .sup.1H-NMR (major enantiomer) see Table 1.

[1211] The compound of the formula (I-075) listed in Table 1 below can be prepared analogously.

Synthesis of 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-N-cyclopropyl-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxamide (example I-076)

[1212] ##STR00110##

[1213] To a stirred mixture of 141.2 mg (24.7 mmol) cyclopropane amine and 356.6 mg (4.9 mmol) trimethyl aluminium in dichloromethane (40 mL) was added 750.0 mg (1.6 mmol) methyl 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl] amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxylate (example I-072, step 2) dropwise at room temperature under a nitrogen atmosphere. The resulting mixture was stirred for 3 h at room temperature under a nitrogen atmosphere. The resulting mixture was washed with water (3×30 mL). The organic layer was dried by Na.sub.2SO.sub.4 and concentrated under reduced pressure. The crude product was purified by preparative HPLC (XBridge Shield RP18 OBD column, 19×250 mm, 10 um; mobile phase A: water (10 mmol/L NH.sub.4HCO.sub.3), mobile phase B: acetonitrile; Flow rate: 25 mL/min; Gradient: 47 B to 47 B in 7 min; 254/220 nm) to afford 480.0 mg (yield: 60.6%) of the racemic title compound as a white solid. The resulting product was further purified by chiral HPLC column to afford 112.7 mg (yield: 24%) of 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-N-cyclopropyl-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxamide (major enantiomer) as a white solid and 87.1 mg (yield: 18%) of the minor enantiomer as a white solid.

[1214] .sup.1H-NMR (major enentiomer) see Table 1.

[1215] The compound of the formulae (I-077)-(I-079) listed in Table 1 below can be prepared analogously.

Synthesis of 3-chloro-N-[1-(5-cyano-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5-(trifluoromethyl)benzamide (example I-080)

[1216] ##STR00111##

[1217] To a stirred mixture of 560.0 mg (1.3 mmol) 5-[1-[[3-chloro-5-(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazole-3-carboxamide (example I-074) and 644.3 mg (6.4 mmol) triethylamine in THF (20 mL) 1069.79 mg (5.093 mmol) trifluoroacetic acid anhydride (TFAA) was added dropwise at 0° C. The resulting mixture was stirred for overnight at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by preparative TLC (petrolether/EtOAc 3:1) to afford 430.0 mg (yield: 80.1%) of the racemic 3-chloro-N-[1-(5-cyano-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5-(trifluoromethyl)benzamide as a white solid. The resulting product was purified by chiral HPLC column to afford 122.5 mg (yield: 28%) 3-chloro-N-[1-(5-cyano-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-5-(trifluoromethyl)benzamide (major enantiomer) as a white solid and 109.5 mg (yield: 26%) enantiomer compound as a white solid.

[1218] .sup.1H-NMR (major enantiomer) see Table 1.

[1219] The compound of the formula (I-081) listed in Table 1 below can be prepared analogously.

Synthesis of N-[1-(5-benzyl-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-82)

[1220] ##STR00112##

Step 1

2-[(1S)-1-[3-(amino)-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione-hydrochloride

[1221] ##STR00113##

[1222] 8.8 g (17.1 mmol) 2-[(1S)-1-[3-(N-Boc-amino)-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione (synthesisized according to example I-001, steps 1-2), was treated with 4N HCl in dioxane solution (150 ml) and the reaction mixture was stirred 18 h at room temperature. Then the reaction mixture was concentrated and the solid residue was used for the halogen introduction (step 4) without purification.

[1223] Formula: C.sub.16H.sub.14ClN.sub.7O.sub.2 Molecular weight: 371.78 g/mol

[1224] HPLC-MS (ESI positive) [m/z]: 336.2 [M−HCl].sup.+

Step 2

2-[1-(5-Iodo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]isoindoline-1,3-dione

[1225] ##STR00114##

[1226] To 11.22 g (30.17 mmol) 2-[(1S)-1-[3-(amino)-1-pyrimidinyl)-1H-1,2,4-triazol-5-yl)ethyl]-1H-isoindole-1,3(2H)-dione-hydrochloride in acetonitrile (448 ml), 180.95 g (675.64 mmol) diiodomethane was added (argon atmosphere), and then the reaction mixture was treated drop by drop at room temperature with 14.31 g (138.82 mmol) tert-butyl nitrite. Then the reaction mixture was stirred 3 h at 80° C. temperature. The reaction mixture was treated with acetic acid ethyl ester and then extracted with a saturated NaCl solution. Afterwards the solvent was evaporated in vacuo the crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 8.1 g (purity: 99%; yield: 60%) of the racemic title compound.

[1227] Formula: C.sub.16H.sub.11IN.sub.6O.sub.2 Molecular weight: 446.20 g/mol

[1228] HPLC-MS acid (ESI positive): 447.0 [M+H].sup.+

[1229] .sup.1H-NMR peaklist (600 MHz, DMSO-d.sub.6, ppm): δ=8.7920 (10.1); 8.7839 (10.2); 8.7780 (7.2); 8.7699 (7.2); 7.9209 (0.5); 7.9156 (0.6); 7.9124 (0.5); 7.9111 (0.6); 7.9065 (1.1); 7.8865 (1.1); 7.8821 (0.6); 7.8775 (0.6); 7.8723 (0.6); 7.8272 (1.6); 7.8220 (2.5); 7.8200 (3.0); 7.8159 (4.7); 7.8122 (12.5); 7.8073 (16.0); 7.8036 (5.1); 7.8010 (3.2); 7.7995 (4.0); 7.7971 (5.8); 7.7928 (3.1); 7.7889 (1.8); 7.7827 (1.6); 7.5145 (2.8); 7.5064 (5.5); 7.4983 (2.8); 7.4911 (2.0); 7.4830 (3.8); 7.4750 (1.9); 6.1032 (0.8); 6.0915 (3.1); 6.0798 (3.5); 6.0672 (2.7); 6.0553 (2.2); 6.0436 (0.6); 4.8841 (0.6); 4.8719 (0.6); 3.3419 (6.3); 2.5116 (11.4); 2.5087 (15.6); 2.5057 (11.5); 2.5028 (5.4); 2.0892 (0.4); 1.7986 (10.2); 1.7870 (12.4); 1.7772 (7.0); 1.7441 (3.2); 1.5644 (2.1); 1.5522 (2.1); 1.3888 (0.7); 1.2301 (8.8)

Step 3

2-[1-(5-Benzyl-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]isoindoline-1,3-dione

[1230] ##STR00115##

[1231] To 250.0 mg (0.56 mmol) 2-[1-(5-iodo-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]isoindoline-1,3-dione in THF (20 mL), 397.39 mg (1.68 mmol) benzyl zinc bromide (0.5M in THF, ABCR) and 25.0 mg (0.02 mmol) tetrakis(triphenylphosphine)palladium(0) were added, and the reaction mixture was stirred 2 h at 50° C. under argon atmosphere. The reaction mixture was filtered, concentrated and the residue was purified by HPLC with a MeCN/water gradient (acid) to afford 176.0 mg (purity: 100%; yield: 76%) of the racemic title compound.

[1232] Formula: C.sub.23H.sub.18N.sub.6O.sub.2 Molecular weight: 410.43 g/mol

[1233] HPLC-MS acid (ESI positive) [m/z]: 411.2 [M+H].sup.+

[1234] .sup.1H-NMR peaklist (600 MHz, d6-DMSO-d.sub.6, ppm): δ=8.7418 (15.2); 8.7337 (15.4); 7.8139 (2.4); 7.8096 (1.8); 7.8070 (3.4); 7.8029 (4.0); 7.7989 (12.4); 7.7928 (12.7); 7.7887 (4.4); 7.7850 (3.4); 7.7820 (1.7); 7.7777 (2.4); 7.4318 (4.2); 7.4237 (8.1); 7.4157 (4.1); 7.3451 (1.8); 7.3422 (2.7); 7.3311 (8.7); 7.3291 (7.2); 7.3252 (8.8); 7.3212 (1.3); 7.3131 (7.4); 7.3105 (2.4); 7.2999 (2.7); 7.2441 (1.2); 7.2415 (1.9); 7.2384 (1.0); 7.2299 (2.7); 7.2210 (0.7); 7.2183 (1.2); 7.2155 (0.6); 6.0709 (1.1); 6.0592 (4.4); 6.0474 (4.5); 6.0357 (1.1); 4.0926 (16.0); 3.3235 (100.8); 2.6176 (0.3); 2.6145 (0.4); 2.5235 (1.0); 2.5205 (1.3); 2.5174 (1.3); 2.5085 (24.5); 2.5055 (51.6); 2.5025 (71.7); 2.4994 (53.3); 2.4965 (25.2); 2.3894 (0.3); 2.3864 (0.4); 2.3834 (0.3); 2.0748 (12.6); 1.7921 (14.2); 1.7804 (14.2); −0.0001 (1.2)

Step 4

1-(5-Benzyl-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine (INT-015)

[1235] ##STR00116##

[1236] To 913.0 mg (2.22 mmol) 2-[1-(5-benzyl-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]isoindoline-1,3-dione in ethanol (30.4 mL), 506.2 mg (5.56 mmol) hydrazine-hydrate was added, and the reaction mixture was heated under reflux. The reaction mixture was stirred and heated under reflux 2 h, acetone (2 mL) was added and the stirring was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was separated to afford 623.0 mg (yield: 99%) of the racemic intermediate (INT-015), which was used for the N-acylation reaction (step 5) without purification.

[1237] Formula: C.sub.15H.sub.16N.sub.6 Molecular weight: 280.33 g/mol

[1238] HPLC-MS acid (ESI positive): 281.1 [M+H].sup.+

[1239] The intermediates of the formulae (INT-016)-(INT-017) listed in Table 2 below can be prepared analogously.

Step 5

N-[1-(5-benzyl-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-82)

[1240] To 112.4 mg (0.40 mmol) (1S)-1-[2-(5-chloro-2-pyridyl)-5-methylsulfanyl-1,2,4-triazol-3-yl]ethanamine (INT-015), 117.0 mg (0.44 mmol) bis-3,5-(trifluoromethyl)-benzoic acid, 79.7 mg (0.61 mmol) DIPEA in DMF (3.5 mL), 206.0 mg (0.54 mmol) HATU was added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered, concentrated and the residue was purified by HPLC with a MeCN/water gradient (acid) to afford 43.4 mg (purity: 100%; yield: 19%) of the racemic title compound.

[1241] Formula: C.sub.24H.sub.18C.sub.3FN.sub.6O Molecular weight: 520.44 g/mol

[1242] HPLC-MS acid (ESI positive): 521.2 [M+H].sup.+

[1243] The compounds of the formula (I-83)-(I-87) and (I-109)-(I-111) listed in Table 1 below can be prepared analogously.

Synthesis of tert-butyl N-[5-[1-[(3,5-dibromobenzoyl)amino]ethyl]-1-[5-(morpholine-4-carbonyl)-2-pyridyl]-1,2,4-triazol-3-yl]carbamate (example I-106)

[1244] ##STR00117##

Step 1: 6-[3-(tert-butoxycarbonylamino)-5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1,2,4-triazol-1-yl]pyridine-3-carboxylic acid

[1245] ##STR00118##

[1246] To a solution of 1.2 g (3.06 mmol) tert-butyl N—[(E)-N-[(2S)-2-(1,3-dioxoisoindolin-2-yl)propanoyl]-C-methylsulfanyl-carbonimidoyl]carbamate in pyridine (10 ml), 0.7 g (3.69 mmol) 6-hydrazinopyridine-3-carboxylic acid hydrochloride was added and the reaction mixture was stirred for 3.5 h at 80° C. temperature. Afterwards the solvent was evaporated in vacuo. The racemic crude product (2.7 g, purity: 56%) was used in step 2 without purification.

[1247] Formula: C.sub.23H.sub.22N.sub.6O.sub.6 Molecular weight: 478.46 g/mol

[1248] HPLC-MS (ESI positive) [m/z]: 479.2 [M+H].sup.+

Step 2: tert-Butyl N-[5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1-[5-(morpholine-4-carbonyl)-2-pyridyl]-1,2,4-triazol-3-yl]carbamate

[1249] ##STR00119##

[1250] To a solution of 2.7 g (3.16 mmol) 6-[3-(tert-butoxycarbonylamino)-5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1,2,4-triazol-1-yl]pyridine-3-carboxylic acid (step 1) in acetonitril (50 ml), 1.4 g (3.79 mmol) HATU, 531 mg (4.10 mmol) DIPEA and 330 mg (3.76 mmol) morpholine were added and the reaction mixture was stirred at room temperature overnight. Afterwards the solvent was evaporated in vacuo. The crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 1.3 g (purity: 80%; yield: 60%) of the racemic title compound.

[1251] Formula: C.sub.27H.sub.29N.sub.7O.sub.6 Molecular weight: 547.57 g/mol

[1252] HPLC-MS (ESI positive) [m/z]: 548.2 [M+H].sup.+

Step 3: tert-butyl N-[5-(1-aminoethyl)-1-[5-(morpholine-4-carbonyl)-2-pyridyl]-1,2,4-triazol-3-yl]carbamate (INT-018)

[1253] ##STR00120##

[1254] To 880 mg (1.60 mmol) tert-butyl N-[5-[1-(1,3-dioxoisoindolin-2-yl)ethyl]-1-[5-(morpholine-4-carbonyl)-2-pyridyl]-1,2,4-triazol-3-yl]carbamate (step 2) in ethanol (20 mL), 370 mg (4.06 mmol) hydrazine-hydrate were added, and the reaction mixture was heated under reflux. After 30 minutes a colorless precipitate was formed. The reaction mixture was stirred and heated under reflux two additional hours, acetone (2 mL) was added and the heating was continued for further 30 minutes. The reaction mixture was concentrated and the solid residue was treated with ethanol. After filtration, the filtrate was evaporated under reduced pressure to afford 900 mg of the racemic intermediate, which was used in step 4 without purification.

[1255] Formula: C.sub.19H.sub.27N.sub.7O.sub.4 Molecular weight: 417.21 g/mol

[1256] HPLC-MS (ESI positive) [m/z]: 418.2 [M+H].sup.+

[1257] The intermediate of the formula (INT-019) listed in Table 2 below can be prepared analogously.

Step 4: tert-butyl N-[5-[I-[(3,5-dibromobenzoyl)amino]ethyl]-1-[5-(morpholine-4-carbonyl)-2-pyridyl]-1,2,4-triazol-3-yl]carbamate

[1258] To 900 mg (2.15 mmol) tert-butyl N-[5-(1-aminoethyl)-1-[5-(morpholine-4-carbonyl)-2-pyridyl]-1,2,4-triazol-3-yl]carbamate (INT-018), 297 mg (1.03 mmol) 3,5-dibromobenzoic acid, 170 mg (1.31 mmol) DIPEA in acetonitrile (15 mL), 460 mg (1.21 mmol) HATU were added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the solid residue was treated with dichloromethane and then extracted with a saturated aqueous NaHCO.sub.3 solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining crude product was chromatographed with a cyclohexane/acetone gradient on silica gel to afford 439 mg (purity: 98%; yield: 62%) of the racemic title compound.

[1259] Formula: C.sub.26H.sub.29Br.sub.2N.sub.7O.sub.5 Molecular weight: 679.38 g/mol

[1260] HPLC-MS (ESI positive) [m/z]: 680.1 [M+H].sup.+

Synthesis of N-[1-[5-amino-2-[5-(morpholine-4-carbonyl)-2-pyridyl]-1,2,4-triazol-3-yl]ethyl]-3,5-dibromo-benzamide (example I-107)

[1261] ##STR00121##

[1262] 380 mg (0.55 mmol) tert-butyl N-[5-[1-[(3,5-dibromobenzoyl)amino]ethyl]-1-[5-(morpholine-4-carbonyl)-2-pyridyl]-1,2,4-triazol-3-yl]carbamate were dissolved in 4N HCl-dioxane solution (5 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 103 mg (purity: 96%) of the racemic title compound.

[1263] Formula: C.sub.21H.sub.21Br.sub.2N.sub.7O.sub.3 Molecular weight: 579.26 g/mol

[1264] HPLC-MS neutral (ESI-positive) [m/z]: 580.0 [M+H].sup.+

Synthesis of N-[(1S)-1-[5-(methylamino)-2-[5-(morpholine-4-carbonyl)thiazol-2-yl]-1,2,4-triazol-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-126)

[1265] ##STR00122##

Step 1: (2-hydrazinothiazol-5-yl)-morpholino-methanone

[1266] ##STR00123##

[1267] A mixture of 1.3 g (5.58 mmol) (2-chlorothiazol-5-yl)-morpholino-methanone (preparation, see WO 2014118186 A1) in THF (56.5 mL) and 11.2 ml (11.1 mmol) of a 1M solution of hydrazine in THF was refluxed for 2.5 h. After cooling to room temperature, the mixture was evaporated. The remaining 1.3 g crude product (yield: 99.8%) of the title compound was used for step 2.

Step 2: tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-[5-(morpholine-4-carbonyl)thiazol-2-yl]-1,2,4-triazol-3-yl]-N-methyl-carbamate

[1268] ##STR00124##

[1269] To 300 mg (1.58 mmol)N-Boc-alanin (Boc-Ala-OH purchased from Sigma-Aldrich) und 323.9 mg (1.58 mmol) tert-butyl N-methyl-N-(methylsulfanyl-carbonimidoyl)carbamate (preparation, see example I-009, step 1) in N,N-dimethylformamide (20 mL), 481.3 mg (4.75 mmol) DIPEA and 904.3 mg (2.37 mmol) HATU were added, and the reaction mixture was stirred 3 hours at room temperature. Then, to the in-situ formed tert-butyl N—[N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]-C-methylsulfanyl-carbonimidoyl]-N-methyl-carbamate acetic acid (0.109 mL), 434.4 mg (1.90 mmol) (2-hydrazinothiazol-5-yl)-morpholino-methanone were added and the reaction mixture was stirred for 1 h at 50° C. temperature. Afterwards, the reaction mixture was treated with ethyl acetate and then extracted with a saturated aqueous NaCl solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining crude product was chromatographed by HPLC with a water/acetonitrile gradient (neutral) to afford 273.6 mg (purity: 100%; yield: 22%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=100%; R.sub.t=13.62 min.

[1270] Formula: C.sub.23H.sub.35F.sub.6N.sub.7O.sub.6S Molecular weight: 537.64 g/mol

[1271] UPLC-MS neutral [m/z]: 538.2 [M+H].sup.+

Step 3: [2-[5-[(1S)-1-aminoethyl]-3-(methylamino)-1,2,4-triazol-1-yl]thiazol-5-yl]-morpholino-methanone (INT-020)

[1272] ##STR00125##

[1273] 273.6 mg (0.55 mmol) tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-[5-(morpholine-4-carbonyl)thiazol-2-yl]-1,2,4-triazol-3-yl]-N-methyl-carbamate were dissolved in 4N HCl-dioxane solution (50 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 169 mg (purity: 98%) of the title compound, which can be used for the coupling reaction in step 4.

[1274] Formula: C.sub.13H.sub.19N.sub.7O.sub.2S Molecular weight: 337.40 g/mol

Step 4: N-[(1S)-1-[5-(methylamino)-2-[5-(morpholine-4-carbonyl)thiazol-2-yl]-1,2,4-triazol-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-126)

[1275] To 164.8 mg (0.48 mmol) [2-[5-[(1S)-1-aminoethyl]-3-(methylamino)-1,2,4-triazol-1-yl]thiazol-5-yl]-morpholino-methanone (INT-020), 130.0 mg (0.48 mmol) bis-3,5-(trifluoromethyl)-benzoic acid, 82.1 mg (0.63 mmol) DIPEA in N,N-dimethylformamide (4.5 mL), 22.9 mg (0.58 mmol) HATU were added, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the remaining crude product was chromatographed by preparative HPLC with a water/acetonitrile gradient (neutral) to afford 142.1 mg (purity: 96%; yield: 48%) of the title compound.

[1276] Formula: C.sub.22H.sub.21F.sub.6N.sub.7O.sub.3S Molecular weight: 577.51 g/mol

[1277] HPLC-MS neutral (ESI-positive) [m/z]: 578.1 [M+H].sup.+

[1278] .sup.13C-NMR peaklist (150.9 MHz, d.sub.6-DMSO): δ=164.1849 (4.3); 163.2775 (3.2); 160.2210 (3.6); 159.8269 (3.5); 158.4937 (4.1); 141.9436 (3.6); 135.9002 (3.7); 131.0035 (0.8); 130.7826 (2.6); 130.5621 (2.6); 130.3417 (0.8); 129.1643 (4.1); 128.5089 (2.7); 125.9904 (0.8); 125.3732 (1.0); 124.1812 (2.2); 122.3721 (2.2); 120.5633 (0.5); 66.1823 (6.1); 43.8331 (4.4); 40.2357 (9.7); 40.1163 (52.1); 39.9775 (155.2); 39.8386 (304.3); 39.6995 (356.3); 39.5604 (301.7); 39.4213 (151.0); 39.2822 (49.0); 29.3257 (6.4); 18.4308 (7.0); 1.3248 (0.6); 0.2743 (2.3) ppm.

Synthesis of N-[(1S)-1-[5-(methylamino)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-127)

[1279] ##STR00126##

Step 1: tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate

[1280] ##STR00127##

[1281] To 1.0 g (5.28 mmol)N-Boc-alanin (Boc-Ala-OH purchased from Sigma-Aldrich) und 1.1 g (5.28 mmol) tert-butyl N-methyl-N-(methylsulfanyl-carbonimidoyl)carbamate (preparation, see example I-009, step 1) in N,N-dimethylformamide (66.6 mL), 1.6 g (15.8 mmol) DIPEA and 3.0 g (7.92 mmol) HATU were added, and the reaction mixture was stirred 3 hours at room temperature. Then, to the in-situ formed tert-butyl N—[N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]-C-methylsulfanyl-carbonimidoyl]-N-methyl-carbamate acetic acid (0.327 mL), 628.7 mg (5.71 mmol) pyrimidin-2-ylhydrazine were added and the reaction mixture was stirred for 1 h at 50° C. temperature. Afterwards, the reaction mixture was treated with ethyl acetate and then extracted with a saturated aqueous NaCl solution and water. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining crude product was chromatographed by HPLC with a water/acetonitrile gradient (neutral) to afford 970 mg (purity: 100%; yield: 49%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=100%; R.sub.t=10.67 min.

[1282] Formula: C.sub.19H.sub.29N.sub.7O.sub.4 Molecular weight: 419.48 g/mol

[1283] HPLC-MS neutral [m/z]: 420.2 [M+H].sup.+

[1284] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ=8.9825 (1.4); 8.9704 (1.4); 7.6350 (0.7); 7.6228 (1.3); 7.6107 (0.7); 3.3275 (13.3); 3.2074 (6.7); 2.5122 (4.7); 2.5079 (9.0); 2.5034 (11.5); 2.4989 (8.2); 2.4945 (3.9); 2.0751 (0.5); 1.4508 (1.4); 1.4305 (16.0); 1.2951 (5.2); 1.0440 (0.4); 0.0079 (0.6); −0.0002 (14.4); −0.0085 (0.6) ppm.

Step 2: 5-[(1S)-1-aminoethyl]-N-methyl-1-pyrimidin-2-yl-1,2,4-triazol-3-amine hydrochlorid (INT-021)

[1285] ##STR00128##

[1286] 1.75 g (4.18 mmol) tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate were dissolved in 4N HCl-dioxane solution (35 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 1.0 g (yield: 99%) of the title compound, which can be used for the coupling reaction in step 3.

[1287] Formula: C.sub.9H.sub.13N.sub.7 HCl Molecular weight: 255.71 g/mol

[1288] HPLC-MS acid (ESI-positive) [m/z]: 220.1 [M−HCl].sup.+

Step 3: N-[(1S)-1-[5-(methylamino)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]-3,5-bis(trifluoromethyl) benzamide (example I-127)

[1289] To 200.0 mg (0.75 mmol) bis-3,5-(trifluoromethyl)-benzoic acid, 126.2 mg (0.97 mmol) DIPEA in N,N-dimethylformamide (6.9 mL) and 342.9 mg (0.9 mmol) HATU were added, and the reaction mixture was stirred for 10 minutes. Then 164.8 mg (0.48 mmol) 5-[(1S)-1-aminoethyl]-N-methyl-1-pyrimidin-2-yl-1,2,4-triazol-3-amine (INT-021) were added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the remaining crude product was chromatographed by preparative HPLC with a water/acetonitrile gradient (neutral) to afford 181.3 mg (purity: 100%; yield: 52%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=100%; R.sub.t=8.88 min.

[1290] Formula: C.sub.18H.sub.15F.sub.6N.sub.7O Molecular weight: 459.35 g/mol

[1291] HPLC-MS neutral (ESI-positive) [m/z]: 460.1 [M+H].sup.+

[1292] .sup.13C-NMR peaklist (150.9 MHz, d.sub.6-DMSO): δ=163.8284 (3.1); 163.0033 (2.4); 159.3393 (3.0); 159.2264 (7.0); 155.3047 (2.4); 136.1059 (2.8); 130.9315 (0.5); 130.7114 (1.8); 130.4909 (1.9); 130.2706 (0.6); 128.4171 (2.0); 128.3979 (2.0); 125.9791 (0.5); 125.2183 (0.8); 124.1697 (1.5); 122.3607 (1.4); 120.5516 (0.4); 119.2484 (2.9); 44.2100 (3.8); 40.3488 (0.3); 40.2360 (5.8); 40.1163 (31.6); 39.9776 (94.0); 39.8386 (184.3); 39.6996 (215.8); 39.5605 (182.8); 39.4213 (91.5); 39.2822 (29.8); 29.5907 (5.2); 18.9774 (5.1) ppm.

[1293] The compounds of the formula (I-128)-(I-132), (I-136), (I-137), (I-142)-(I-143), (I-180)-(I-186), (I-202), (I-206)-(I-210), (I-212), (I-217)-(I-219), (I-223), (I-226)-(I-228) and (I-231) listed in Table 1 below can be prepared analogously.

[1294] Alternatively, the compound of the formula (I-127) can be prepared by chromatographic separation of the racemic compound of the formula (I-009) forming the compound of the formula (I-133) and following N-Boc group cleavage.

Step 1: tert-butyl N-[5-[(1S)-1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate (example I-133)

[1295] ##STR00129##

[1296] 2.3 g (0.41 mmol) example 1-009 (crude material) was separated by SFC-chromatography on a chiral stationary phase (Chiracel OD-H). The substances were isolated from the fractions by evaporation at 40° C. under vacuum. The last used solvent was methanol and the substance was dried at 10 mbar for 10 min to afford two charges of the title compound, 721 mg (ee-value=99%, R.sub.t=2.7 min) and 98 mg (ee-value=92.3% R.sub.t=2.7 min).

[1297] As side product 860 mg (ee-value=98.9%; R.sub.t=2.4 min) of the tert-butyl N-[5-[(1R)-1-[[3,5-bis(trifluoromethyl) benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate was isolated.

Step 2: N-[(1S)-1-[5-(methylamino)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]-3,5-bis(trifluoromethyl) benzamide (example I-127)

[1298] 721 mg (1.28 mmol) tert-butyl N-[5-[(1S)-1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate (example I-133) were dissolved in 4N HCl-dioxane solution (10 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 101 mg (purity: 99.1; yield: 17%) of the title compound together with 297 mg unsoluble solid. Specific rotation [α].sub.589=+107.5° (5.0 ml, DMSO at 20° C.).

[1299] Formula: C.sub.18H.sub.15F.sub.6N.sub.7O Molecular weight: 459.35 g/mol

[1300] HPLC-MS neutral (ESI-positive) [m/z]: 460.1 [M+H].sup.+

[1301] .sup.1H-NMR peaklist (600.1 MHz, d.sub.6-DMSO): δ=9.4999 (3.1); 9.4880 (3.1); 8.8706 (15.4); 8.8625 (15.5); 8.4678 (10.6); 8.3124 (4.6); 7.4473 (4.1); 7.4393 (7.7); 7.4312 (3.9); 6.2352 (0.9); 6.2269 (3.0); 6.2184 (2.9); 6.2100 (0.8); 6.0711 (0.5); 6.0596 (2.3); 6.0479 (3.6); 6.0362 (2.3); 6.0246 (0.5); 3.3436 (0.5); 3.3167 (538.4); 2.7470 (15.9); 2.7386 (16.0); 2.6188 (1.7); 2.6160 (3.8); 2.6130 (5.2); 2.6100 (3.8); 2.6070 (1.8); 2.5371 (0.6); 2.5220 (10.4); 2.5189 (13.2); 2.5158 (13.4); 2.5069 (290.8); 2.5040 (615.6); 2.5009 (852.6); 2.4979 (639.4); 2.4950 (308.9); 2.4552 (0.5); 2.4476 (0.4); 2.3907 (1.8); 2.3879 (3.8); 2.3849 (5.3); 2.3818 (3.9); 2.3789 (1.9); 2.0738 (1.2); 1.6148 (12.5); 1.6032 (12.6); −0.0001 (5.3) ppm.

Synthesis of N-[(1S)-1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3,5-bis(trifluoromethyl) benzamide (example I-134)

[1302] ##STR00130##

Step 1: tert-butyl N-[5-[(1S)-1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate (example I-135)

[1303] ##STR00131##

[1304] To 2.3 g (8.91 mmol) bis-3,5-(trifluoromethyl)-benzoic acid in acetonitrile (162 mL), 1.6 g (12.3 mmol) DIPEA and 3.8 g (10.0 mmol) HATU were added, and the reaction mixture was stirred for 10 minutes. Then 2.7 g (8.91 mmol) racemic tert-butyl N-[5-(1-aminoethyl)-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate (INT-001) were added and the reaction mixture was stirred at room temperature overnight. Afterwards, the reaction mixture was treated with water and then extracted with dichloromethane. The organic phase was separated, dried over Mg.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining crude product was chromatographed by preparative HPLC with a water/acetonitrile gradient (neutral) to afford 862 mg (purity: 98%) of a racemic mixture, which was separated by SFC-chromatography on a chiral stationary phase (Chiracel OD-H). The substances were isolated from the fractions by evaporation at 40° C. under vacuum. The substance was dried at 10 mbar for 10 min to afford two charges, 270 mg (yield: 5.5%) of the title compound and 280 mg (yield: 5.8%) of the tert-butyl N-[5-[(1R)-1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl] carbamate.

[1305] Formula: C.sub.22H.sub.21F.sub.6N.sub.7O.sub.3 Molecular weight: 545.44 g/mol

[1306] UPLC-MS neutral [m/z]: 446.2 [M+H].sup.+

Step 2: N-[(1S)-1-(5-amino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3,5-bis(trifluoromethyl) benzamide (example I-134)

[1307] 259 mg (0.47 mmol) tert-butyl N-[5-[(1S)-1-[[3,5-bis(trifluoromethyl)benzoyl]amino]ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]carbamate (example I-135) were dissolved in 4N HCl-dioxane solution (5 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 199 mg (purity: 93; yield: 87.5%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=98.6%; R.sub.t=10.34 min.

[1308] Formula: C.sub.17H.sub.13F.sub.6N.sub.7O Molecular weight: 445.33 g/mol

[1309] HPLC-MS neutral (ESI-positive) [m/z]: 446.1 [M+H].sup.+

[1310] .sup.13C-NMR peaklist (150.9 MHz, d.sub.6-DMSO): δ=162.9407 (1.0); 162.7383 (0.4); 159.2277 (1.0); 158.9032 (0.4); 155.2440 (0.4); 136.0900 (1.2); 130.9293 (0.2); 130.7092 (0.8); 130.4889 (0.9); 130.2682 (0.3); 128.3989 (1.1); 125.9811 (0.2); 125.2194 (0.4); 124.1722 (0.7); 122.3632 (0.7); 119.3218 (0.5); 91.3806 (0.4); 72.3366 (0.3); 70.6930 (0.3); 66.5235 (7.0); 60.3557 (0.3); 59.3842 (0.5); 44.1276 (0.7); 43.7807 (0.2); 40.2357 (6.3); 40.1162 (48.3); 39.9775 (143.6); 39.8385 (281.5); 39.6995 (329.3); 39.5604 (279.1); 39.4213 (139.9); 39.2822 (45.6); 19.0353 (1.3); 18.9788 (0.2); 0.2795 (1.5) ppm.

Synthesis of N-[(1S)-1-[5-(dimethylamino)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-141)

[1311] ##STR00132##

Step 1: tert-Butyl N-[(1S)-1-[5-(dimethylamino)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]carbamate

[1312] ##STR00133##

[1313] To 8.2 g (43.60 mmol)N-Boc-alanin (Boc-Ala-OH purchased from Sigma-Aldrich) in tetrahydrofurane (125 mL), 13.2 g (130.80 mmol) triethylamine (18.2 mL) and 24.8 g (65.40 mmol) HATU were added, and the reaction mixture was stirred for 10 minutes. Then 4.5 g (38.20 mmol) N,N-dimethyl(methylsulfanyl) methanimidamide (can be purchased from Enamine building blocks, 57618-94-7) were added, and the reaction mixture was stirred 1 hour at 80° C. Then, to the in-situ formed tert-butyl N-[(1S)-2-[(E)-[dimethylamino(methylsulfanyl)methylene]amino]-1-methyl-2-oxo-ethyl]carbamate acetic acid (0.93 mL), 628.7 mg (5.71 mmol) pyrimidin-2-ylhydrazine in N,N-dimethylformamide (20 mL) were added and the reaction mixture was stirred for 1 h at 50° C. temperature. Afterwards, tetrahydrofurane was removed under reduced pressure and the reaction mixture was treated with water and then extracted with ethyl acetate. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining crude product was chromatographed by HPLC with a water/acetonitrile gradient (neutral) to afford 4.1 mg (purity: 100%; yield: 90.5%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=99.2%; Rt=9.07 min.

[1314] Formula: C.sub.15H.sub.23N.sub.7O.sub.2 Molecular weight: 333.39 g/mol

[1315] HPLC-MS neutral [m/z]: 334.2 [M+H].sup.+

Step 2: 5-[(1S)-1-aminoethyl]-N,N-dimethyl-1-pyrimidin-2-yl-1,2,4-triazol-3-amine (INT-022)

[1316] ##STR00134##

[1317] 2.5 g (7.49 mmol) tert-butyl N-[(1S)-1-[5-(dimethylamino)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]carbamate were dissolved in 4N HCl-dioxane solution (50 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 1.73 g (yield: 99%) of the title compound, which can be used for the coupling reaction in step 3.

[1318] Formula: C.sub.10H.sub.15N.sub.7 Molecular weight: 233.27 g/mol

[1319] HPLC-MS neutral (ESI-positive) [m/z]: 234.2 [M+H].sup.+

Step 3: N-[(1S)-1-[5-(Dimethylamino)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]-3,5-bis (trifluoro-methyl)benzamide (example I-141)

[1320] To 200.0 mg (0.75 mmol) bis-3,5-(trifluoromethyl)-benzoic acid, 126.2 mg (0.97 mmol) DIPEA in N,N-dimethylformamide (6.9 mL) and 342.9 mg (0.9 mmol) HATU were added, and the reaction mixture was stirred for 10 minutes. Then 175.3 mg (0.75 mmol) 5-[(1S)-1-aminoethyl]-N,N-dimethyl-1-pyrimidin-2-yl-1,2,4-triazol-3-amine (INT-022) were added an the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the remaining crude product was chromatographed by preparative HPLC with a water/acetonitrile gradient (neutral) to afford 43.8 mg (purity: 97.5%; yield: 12%) of the title compound.

[1321] Formula: C.sub.19H.sub.17F.sub.6N.sub.7O Molecular weight: 473.38 g/mol

[1322] HPLC-MS neutral (ESI-positive) [m/z]: 474.1 [M+H].sup.+

[1323] .sup.13C-NMR peaklist (150.9 MHz, CD.sub.3CN): δ=165.9962 (1.1); 164.7345 (1.1); 160.2068 (1.6); 159.8730 (6.4); 156.5348 (0.8); 137.6856 (1.4); 132.5785 (0.3); 132.3555 (1.0); 132.1325 (1.1); 131.9095 (0.3); 129.0356 (1.4); 129.0168 (1.4); 126.9883 (0.2); 126.0362 (0.3); 126.0109 (0.6); 125.9860 (0.8); 125.9611 (0.6); 125.9361 (0.3); 125.1852 (0.6); 123.3824 (0.6); 119.9591 (3.3); 118.2929 (140.1); 45.8585 (3.4); 38.4922 (7.0); 19.6631 (3.5); 1.7124 (21.6); 1.5748 (72.5); 1.4371 (150.3); 1.2995 (178.3); 1.1618 (155.5); 1.0943 (6.8); 1.0241 (80.8); 0.9561 (6.2); 0.8865 (29.4); 0.8183 (4.5); 0.6805 (2.8); −0.0852 (1.2); −4.8936 (0.4) ppm.

[1324] The compounds of the formula (I-138)-(I-141), (I-156), (I-157), (I-162), (I-164)-(I-166), (I-170), (I-171), (I-176)-(I-179), (I-191)-(I-194), (I-229), (I-232)-(I-240) and (I-252)-(I-270) listed in Table 1 below can be prepared analogously.

[1325] The racemic compounds of the formula (I-156), (I-157), (I-162), (I-164)-(I-166), (I-171) and (I-191)-(I-194) listed in Table 1 below can be prepared analogously by using racemic N-Boc-alanin as starting component.

Synthesis of N-[(1S)-1-(5-morpholino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-145)

[1326] ##STR00135##

Step 1: tert-Butyl N-[(1S)-1-(5-morpholino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]carbamate

[1327] ##STR00136##

[1328] To 2.6 g (13.67 mmol)N-Boc-alanin (Boc-Ala-OH purchased from Sigma-Aldrich) and 8.8 g (20.51 mmol) HATU in N,N-dimethylformamide (133 mL), 4.1 g (41.0 mmol) DIPEA (5.7 mL) and were added, and the reaction mixture was stirred for 10 minutes. Then 4.5 g (38.20 mmol) morpholine-4-carboximidothioic acid methyl ester (can be purchased from Chemieliva Pharmaceutical Product List, 89269-30-7) were added, and the reaction mixture was stirred 3 hour at room temperature. Then, to the in-situ formed methyl (4E)-N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]morpholine-4-carboximido-thioate acetic acid (0.93 mL), 1.8 g (16.41 mmol) pyrimidin-2-ylhydrazine in N,N-dimethylformamide (100 mL) were added and the reaction mixture was stirred for 1 h at 50° C. and 18 hours at room temperature. Afterwards, N,N-dimethylformamide was removed under reduced pressure and the reaction mixture treated with water and then extracted with ethyl acetate. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining crude product was chromatographed by HPLC with a water/acetonitrile gradient (neutral) to afford 1.2 g (purity: 99%; yield: 23%) of the title compound.

[1329] Formula: C.sub.17H.sub.25N.sub.7O.sub.3 Molecular weight: 375.43 g/mol

[1330] HPLC-MS acid [m/z]: 376.2 [M+H].sup.+

Step 2: (1S)-1-(5-morpholino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine-hydrochlorid (INT-023) (JES 13786-1-1)

[1331] ##STR00137##

[1332] 1.19 g (3.17 mmol) tert-butyl N-[(1S)-1-(5-morpholino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]carbamate were dissolved in 4N HCl-dioxane solution (30 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 1.1 g crude product (yield: 109%) of the title compound, which can be used for the coupling reaction in step 3.

[1333] Formula: C.sub.12H.sub.17N.sub.7O HCl Molecular weight: 311.77 g/mol

[1334] HPLC-MS neutral (ESI-positive) [m/z]: 276.2 [M−HCl].sup.+

Step 3: N-[(1S)-1-(5-Morpholino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-145)

[1335] To 200.0 mg (0.75 mmol) bis-3,5-(trifluoromethyl)-benzoic acid, 126.2 mg (0.97 mmol) DIPEA in N,N-dimethylformamide (6.9 mL) and 342.9 mg (0.9 mmol) HATU were added, and the reaction mixture was stirred for 10 minutes. Then 175.3 mg (0.75 mmol) (1S)-1-(5-morpholino-2-pyrimidin-2-yl-1,2,4-triazol-3-yl)ethanamine-hydrochlorid (INT-023) were added an the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the remaining crude product was chromatographed by preparative HPLC with a water/acetonitrile gradient (neutral) to afford 144.6 mg (purity: 100%; yield: 37%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=100%; R.sub.t=9.86 min.

[1336] Formula: C.sub.21H.sub.19F.sub.6N.sub.7O.sub.2 Molecular weight: 515.42 g/mol

[1337] UPLC-MS neutral (ESI-positive) [m/z]: 516.2 [M+H].sup.+

[1338] .sup.13C-NMR peaklist (150.9 MHz, d6-DMSO): δ=164.1457 (2.8); 163.1322 (2.2); 159.3835 (3.9); 159.3678 (7.0); 155.2292 (2.2); 136.0798 (2.6); 130.9320 (0.5); 130.7115 (1.7); 130.4912 (1.8); 130.2705 (0.6); 128.4139 (1.9); 125.9634 (0.5); 125.2398 (0.8); 124.1541 (1.4); 122.3451 (1.3); 120.5362 (0.4); 119.8711 (2.7); 65.7703 (6.3); 46.4104 (6.2); 44.0056 (3.5); 40.2359 (4.5); 40.1162 (23.9); 39.9775 (71.2); 39.8386 (139.6); 39.6995 (163.5); 39.5604 (138.5); 39.4213 (69.4); 39.2822 (22.5); 18.9118 (4.8); 0.2708 (1.4)

[1339] The compounds of the formula (I-146), (I-147), (I-158)-(I-161), (I-174), (I-175), (I-195), (I-197), (I-199), (I-201) and (I-204) listed in Table 1 (wherein R.sup.5 is morpholinyl) below can be prepared analogously. The racemic compounds of the formula (I-158)-(I-161) and (I-201) listed in Table 1 (wherein R.sup.5 is morpholinyl) below can be prepared analogously by using racemic N-Boc-alanin as starting component.

[1340] The compounds of the formula (I-196), (I-198), (I-200) and (I-220)-(I-222) listed in Table 1 (wherein R.sup.5 is piperidinyl) below can be prepared analogously.

[1341] The racemic compounds of the formula (I-196), (I-198) and (I-200) listed in Table 1 (wherein R.sup.5 is piperidinyl) below can be prepared analogously by using racemic N-Boc-alanin as starting component.

[1342] The compounds of the formula (I-190), (I-203), (I-224)-(I-225) and (I-230) listed in Table 1 (wherein R.sup.5 is pyrrolidinyl) below can be prepared analogously.

Synthesis of N-[(1S)-1-[5-amino-2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-methylsulfonyl-benzamide (example I-148)

[1343] ##STR00138##

Step 1: tert-butyl N-[(1S)-1-[5-(tert-butoxycarbonylamino)-2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate

[1344] ##STR00139##

[1345] To 4.7 g (24.8 mmol)N-Boc-alanin (Boc-Ala-OH purchased from Sigma-Aldrich) and 14.1 g (37.0 mmol) HATU in N,N-dimethylformamide (50 mL), 7.5 g (74.10 mmol) DIPEA (18.2 mL) and 4.64 g (24.40 mmol) 1-N-Boc-2-methyl-isothiourea (purchased from ABCR) were added, and the reaction mixture was stirred for 3 hours at room temperature. Then, to the in-situ formed tert-butyl N—[(Z)—N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]-C-methylsulfanyl-carbonimidoyl]-N-carbamate acetic acid (3.9 mL), 8.3 g (61.8 mmol) 6-hydrazinopyridine-3-carbonitrile were added and the reaction mixture was stirred for 2 hours at 50° C. temperature. Afterwards, the solvent was removed under reduced pressure and the remaining crude product was chromatographed with a acetone/cyclohexane gradient (neutral) to afford 7.0 g (purity: 88%; yield: 27%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=100%; R.sub.t=11.28 min.

[1346] Formula: C.sub.20H.sub.27N.sub.7O.sub.4 Molecular weight: 429.48 g/mol

[1347] HPLC-MS neutral [m/z]: 230.1 [M+H, cleavage of 2× Boc].sup.+

Step 2: 6-[3-amino-5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile-hydrochloride (INT-025)

[1348] ##STR00140##

[1349] 7.0 g (16.2 mmol) tert-butyl N-[(1S)-1-[5-(tert-butoxycarbonylamino)-2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate were dissolved in 4N HCl-dioxane solution (50 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford 4.8 g crude product (yield: 111%) of the title compound, which can be used for the coupling reaction in step 3. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=70.7%; Rt=1.64 min.

[1350] Formula: C.sub.10H.sub.11N.sub.7 HCl Molecular weight: 265.70 g/mol

Step 3: N-[(1S)-1-[5-amino-2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]-3-chloro-5-methylsulfonyl-benzamide (example I-148)

[1351] To 230.0 mg (0.95 mmol) 3-chloro-5-methylsulfonyl-benzoic acid, 370.0 mg (2.86 mmol) DIPEA in acetonitrile (10 mL) and 434.3 mg (1.14 mmol) HATU were added, and the reaction mixture was stirred for 10 minutes. Then 330.0 mg (1.24 mmol) 6-[3-amino-5-[(1S)-1-aminoethyl]-1,2,4-triazol-1-yl]pyridine-3-carbonitrile-hydrochloride (INT-025) were added an the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the remaining crude product was chromatographed by preparative HPLC with a water/acetonitrile gradient (neutral) to afford 76.0 mg (purity: 100%; yield: 18%) of the title compound.

[1352] Formula: C.sub.11H.sub.16ClN.sub.7O.sub.3S Molecular weight: 445.89 g/mol

[1353] UPLC-MS neutral (ESI-positive) [m/z]: 446.1 [M+H].sup.+

[1354] The compounds of the formula (I-154), (I-155), (I-169), (I-172), (I-173), (I-187)-(I-189), (I-205), (I-211), (I-213)-(I-216) and (I-241)-(I-251) listed in Table 1 below can be prepared analogously.

Synthesis of N-[(1S)-1-[5-[methoxy(methyl)amino]-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-149)

[1355] ##STR00141##

Step 1: tert-butyl N-[(1S)-1-[5-[methoxy(methyl)amino]-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]carbamate

[1356] ##STR00142##

[1357] To 3.0 g (15.85 mmol)N-Boc-alanin (Boc-Ala-OH purchased from Sigma-Aldrich) and 9.0 g (23.78 mmol) HATU in N,N-dimethylformamide (200 mL), 2.1 g (20.61 mmol) DIPEA (2.9 mL) and 2.1 g (15.85 mmol) N-methoxy-N-methyl-carbamimidothioic acid methyl ester (preparation according to WO 9300336 A1) were added, and the reaction mixture was stirred for 3 hours at room temperature. Then, to the in-situ formed methyl N-[(2S)-2-(tert-butoxycarbonylamino)propanoyl]-2-methoxy-propanimido-thioate acetic acid (1.1 mL), 2.09 g (19.0 mmol) pyrimidin-2-yl-hydrazine were added and the reaction mixture was stirred for 1 h at 50° C. temperature. Afterwards, the reaction mixture treated with water and then extracted with ethyl acetate. The organic phase was separated, dried over Na.sub.2SO.sub.4 and the solvent was evaporated under reduced pressure. The remaining crude product was chromatographed by HPLC with a water/acetonitrile gradient (neutral) to afford 891.3 mg (purity: 97%; yield: 16%) of the title compound. The enantiomeric excess of the chiral title compounds has been determined via screen OD_RH (acid): ee-value=100%; R.sub.t=8.70 min.

[1358] Formula: C.sub.15H.sub.23N.sub.7O.sub.3 Molecular weight: 349.39 g/mol

[1359] HPLC-MS neutral [m/z]: 350.2 [M+H].sup.+

[1360] .sup.1H-NMR peaklist (400.2 MHz, d.sub.6-DMSO): δ=8.9480 (4.1); 8.9359 (4.1); 7.5811 (1.9); 7.5689 (3.5); 7.5568 (1.8); 7.5004 (0.6); 7.4805 (0.6); 5.5129 (0.4); 5.4957 (0.6); 5.4789 (0.4); 3.7441 (16.0); 3.3259 (29.4); 3.0877 (14.5); 2.6718 (0.4); 2.5252 (1.6); 2.5204 (2.4); 2.5118 (25.1); 2.5073 (51.0); 2.5028 (66.3); 2.4982 (46.9); 2.4937 (22.1); 2.3296 (0.4); 2.0504 (0.4); 1.5274 (1.1); 1.4358 (2.8); 1.4184 (2.6); 1.3057 (12.5); 1.0489 (0.8); 0.1460 (0.5); 0.0079 (4.6); −0.0002 (122.5); −0.0086 (4.7); −0.1496 (0.5) ppm

Step 2: 5-[(1S)-1-aminoethyl]-N-methoxy-N-methyl-1-pyrimidin-2-yl-1,2,4-triazol-3-amine-hydrochloride (INT-026)

[1361] ##STR00143##

[1362] 870.0 mg (2.49 mmol) tert-butyl N-[(1S)-1-[5-[methoxy(methyl)amino]-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl] carbamate were dissolved in 4N HCl-dioxane solution (18.6 mL) and the mixture was stirred 18 h at room temperature. Then the solvent was evaporated under reduced pressure to afford the title compound, which can be used for the coupling reaction in step 3.

[1363] Formula: C.sub.10H.sub.15N.sub.7O HCl Molecular weight: 285.73 g/mol

[1364] HPLC-MS neutral (ESI-positive) [m/z]: 250.1 [M−HCl].sup.+

Step 3: N-[(1S)-1-[5-[methoxy(methyl)amino]-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide (example I-149)

[1365] To 130.0 mg (0.48 mmol) bis-3,5-(trifluoromethyl)-benzoic acid, 82.0 mg (0.63 mmol) DIPEA in N,N-dimethylformamide (3.25 mL) and 222.9 mg (0.58 mmol) HATU were added, and the reaction mixture was stirred for 10 minutes. Then 139.5 mg (0.48 mmol) 5-[(1S)-1-aminoethyl]-N-methoxy-N-methyl-1-pyrimidin-2-yl-1,2,4-triazol-3-amine-hydrochloride (INT-026) were added an the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the remaining crude product was chromatographed by preparative HPLC with a water/acetonitrile gradient (neutral) to afford 60.3 mg (purity: 100%; yield: 25%) of the title compound.

[1366] Formula: C.sub.19H.sub.17F.sub.6N.sub.7O.sub.2 Molecular weight: 489.38 g/mol

[1367] HPLC-MS neutral (ESI-positive) [m/z]: 490.1 [M+H].sup.+

[1368] The compounds of the formula (I-150)-(I-153) listed in Table 1 below can be prepared analogously.

Synthesis of N-{1-[1-(5-cyano-1,3-thiazol-2-yl)-3-(methylsulfanyl)-1H-1,2,4-triazol-5-yl]ethyl}-3-(methylsulfonyl)-5-(trifluoromethoxy)benzamide (example I-167)

[1369] ##STR00144##

Step 1: 2-hydrazino-1,3-thiazole-5-carbonitrile

[1370] ##STR00145##

[1371] A mixture of 9.00 g (62.2 mmol) 2-chloro-1,3-thiazole-5-carbonitrile and 124.5 ml (124.5 mmol) of a 1 M solution of hydrazine in THF was refluxed for 2 h. After cooling to room temperature, the mixture was evaporated and then the residue was suspended in 50 ml of hot water. The resulting precipitate was filtered, washed with water and dried under vacuo to yield the title compound (9.00 g). Further drying by co-evaporation with absolute toluene resulted in a decrease in mass and this material was used in the next step.

[1372] .sup.1H NMR peak list (DMSO-d.sub.6, 400 MHz): δ=9.7694 (1.7); 7.8727 (13.8); 5.3331 (16.0); 3.3330 (6.9); 2.5083 (12.7); 2.5040 (16.5); 2.4997 (12.5)

Step 2: O-methyl [(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl]carbamothioate

[1373] ##STR00146##

[1374] To a solution of 4.73 g (20.5 mmol) (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) propanoic acid in dichloromethane (30 ml) was added at 0° C. 3.58 ml (41.0 mmol) oxalyl chloride and 0.08 mL N,N-dimethylformamide. The reaction mixture was stirred for 1 h at 0° C. and overnight at room temperature. After this time the solvent and excess oxalyl chloride were evaporated under reduced pressure. The crude residue was dissolved in acetone (40 ml) and then 2.99 g (30.7 mmol) KSCN were added dropwise as a solution in acetone (40 ml). The addition funnel was rinsed with 10 ml acetone and the mixture was stirred at 60° C. for 2 h. After cooling to room temperature 2.1 ml (51 mmol) of methanol were added and the mixture was stirred at 55° C. overnight, cooled to room temperature and evaporated under reduced pressure. The resulting residue was suspended in a mixture of water and EtOAc. After separation of the layers the aqueous phase was extracted with EtOAc. The combined organic layers were washed with water and brine respectively and finally the organic layer was dried over anhydrous Na.sub.2SO.sub.4 and then concentrated under reduced pressure. The crude product was purified by silica gel chromatography to yield 3.69 g of the title compound.

[1375] ESI mass [m/z]: 293.1 [M+H].sup.+

Step 3: 2-{5-[1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-(methylsulfanyl)-1H-1,2,4-triazol-1-yl}-1,3-thiazole-5-carbonitrile

[1376] ##STR00147##

[1377] To a solution of 700 mg (2.39 mmol) O-methyl [(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propanoyl]carbamothioate in ethanol (15 ml) were added 0.36 g (2.4 mmol) 2-hydrazino-1,3-thiazole-5-carbonitrile and the reaction mixture was stirred overnight at 75° C., then for 6 h at 85° C. and again overnight at 75° C. The mixture was cooled to room temperature, evaporated under reduced pressure and the resulting residue was purified by HPLC (H.sub.2O/acetonitrile). This resulted in the isolation of 206 mg 2-{5-[(1S)-1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-methoxy-1H-1,2,4-triazol-1-yl}-1,3-thiazole-5-carbonitrile and 77 mg 2-{5-[1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-(methylsulfanyl)-1H-1,2,4-triazol-1-yl}-1,3-thiazole-5-carbonitrile. The enantiomeric excess of the obtained title compound was not determined.

[1378] ESI mass [m/z]: 397.1 [M+H].sup.+

[1379] .sup.1H-NMR (400 MHz, DMSO-d6): δ=8.37 (s, 1H), 7.85 (s, 4H), 5.95 (q, J=7.2 Hz, 1H), 2.62 (s, 3H), 1.80 (d, J=7.2 Hz, 3H).

Step 4: 2-[5-(1-aminoethyl)-3-(methylsulfanyl)-1H-1,2,4-triazol-1-yl]-1,3-thiazole-5-carbonitrile

[1380] ##STR00148##

[1381] A solution of 75 mg (0.18 mmol) 2-{5-[1-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-3-(methylsulfanyl)-1H-1,2,4-triazol-1-yl}-1,3-thiazole-5-carbonitrile and 0.03 mL hydrazine hydrate in 2 mL ethanol was stirred for 90 min at room temperature. At this point all of the starting material had converted to a mixture of N-{1-[1-(5-cyano-1,3-thiazol-2-yl)-3-(methylsulfanyl)-1H-1,2,4-triazol-5-yl]ethyl}-2-(hydrazinocarbonyl)benzamide and the desired product as determined by HPLC/MS. 2 ml of 1 M hydrochloric acid were added and the resulting mixture was further stirred for 2 h at room temperature. The pH of the reaction mixture was then adjusted to pH 8 by the addition of a sat. aqueous solution of NaHCO.sub.3. Water was added, and the mixture repeatedly extracted with ethyl acetate. The combined organic layers were washed with brine, dried using Na.sub.2SO.sub.4, filtered and the solvent was evaporated under reduced pressure to yield 37 mg of a residue containing 2-[5-(1-aminoethyl)-3-(methylsulfanyl)-1H-1,2,4-triazol-1-yl]-1,3-thiazole-5-carbonitrile which was used for the next step without further purification.

[1382] ESI mass [m/z]: 267.1 [M+H].sup.+

[1383] Step 5: N-{1-[I-(5-cyano-1,3-thiazol-2-yl)-3-(methylsulfanyl)-1H-1,2,4-triazol-5-yl]ethyl}-3-(methylsulfonyl)-5-(trifluoromethoxy)benzamide

[1384] A solution of 41 mg (0.15 mmol) 3-(methylsulfonyl)-5-(trifluoromethoxy)benzoic acid, 100 mg (0.263 mmol) HATU, 0.08 mL (0.5 mmol)N-ethyldiisopropylamine in 2 mL DMF was stirred for 60 min at room temperature. 35 mg of the crude product obtained in step 4 were then added and the mixture stirred over night. The reaction mixture was then diluted with 1 mL acetonitrile and purified directly by HPLC (H.sub.2O/acetonitrile) to provide 23 mg N-{1-[1-(5-cyano-1,3-thiazol-2-yl)-3-(methylsulfanyl)-1H-1,2,4-triazol-5-yl]ethyl}-3-(methylsulfonyl)-5-(trifluoromethoxy)benzamide.

[1385] ESI mass [m/z]: 533.1 [M+H].sup.+

Synthesis of 3-methylsulfonyl-5-(trifluromethoxy)benzoic acid

[1386] ##STR00149##

[1387] A mixture of 2.95 g (17.5 mmol) trans-N,N-dimethylcyclohexane-1-2-diamine and 11.4 g (35 mmol) cesium carbonate in 60 mL DMF was degassed for 30 min by purging with argon. 5 g (17.5 mmol) 3-bromo-5-(trifluoromethoxy)benzoic acid, 3.58 g (35 mmol) sodium methanesulfinate and 3.34 g (17.5 mmol) copper(I) iodide were added and the mixture further purged with argon for 5 min. The mixture was stirred at 120° C. over night, cooled to room temperature and then three times extracted with dichloromethane. The aqueous layer was acidified to pH 2 using concentrated hydrochloric acid and again extracted with dichloromethane. The dichlormethane phase was washed with brine several times. The layers were separated, and the combined organic layers were dried over anhydrous Na.sub.2SO.sub.4 and filtered. The solvent was removed under reduced pressure and the residue triturated with n-pentane, filtered-off and dried to provide 3.2 g of 3-methylsulfonyl-5-(trifluromethoxy)benzoic acid.

[1388] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=14.00 (br s, 1H, COOH), 8.42 (s, 1H), 8.20 (s, 1H), 8.14 (s, 1H), 3.39 (s, 3H).

[1389] ESI mass [m/z]: 285.0 [M+H].sup.+

Synthesis of 3-(difluoromethylsulfonyl)-5-(trifluromethoxy)benzoic acid (INT-039)

Step 1: Methyl 3-(trifluoromethoxy)-5-triisopropylsilylsulfanyl-benzoate

[1390] ##STR00150##

[1391] To a stirred solution of triisopropylsilanethiol (21.45 g, 112 mmol) in toluene (500 mL), under a stream of argon, NaH (5.03 g, 122 mmol, 60% disperse in oil) was added in portions. The mixture was stirred until no more gas evolved. Then methyl 3-bromo-5-(trifluoromethoxy)benzoate (CAS: 1306763-53-0) (30 g, 100 mmol), XantPhos (6.13 g, 11.2 mmol) and Pd.sub.2(dba).sub.3 (4.85 g, 5.3 mmol) were added to the reaction mixture sequentially. The mixture was stirred at 100° C. overnight, cooled to r.t., diluted with EtOAc (500 mL) and filtered through a thin pad of silica gel. After evaporation, crude methyl 3-(trifluoromethoxy)-5-triisopropylsilylsulfanyl-benzoate (50 g, 50% purity by LC/MS, 64 mmol, 57% yield) was obtained and used in the next step without further purification.

Step 2: Methyl 3-(difluoromethylsulfanyl)-5-(trifluoromethoxy)benzoate

[1392] ##STR00151##

[1393] To a stirred solution of crude methyl 3-(trifluoromethoxy)-5-triisopropylsilylsulfanyl-benzoate (50 g, 50% purity by LC/MS, 64 mmol) in DMF (1000 mL) sodium 2-chloro-2,2-difluoroacetate (29.27 g, 192 mmol) and cesium carbonate (62.55 g, 192 mmol) were added under a stream of argon. The mixture was stirred at 100° C. overnight, cooled to r.t., and evaporated under reduced pressure. The residue was dissolved in water (1000 mL) and extracted with EtOAc (5×250 mL). Methyl 3-(difluoromethylsulfanyl)-5-(trifluoromethoxy)benzoate (10.5 g, 34.7 mmol, 54.3% yield) was obtained after column chromatography.

Step 3: Methyl 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoate

[1394] ##STR00152##

[1395] To a solution of methyl 3-(difluoromethylsulfanyl)-5-(trifluoromethoxy)benzoate (10.5 g, 34.7 mmol) in dichloromethane (200 mL) mCPBA (16.35 g, 93.9 mmol, 75% purity) was added in portions at 0° C. under a stream of argon. The mixture was stirred overnight at room temperature and evaporated under reduced pressure. Methyl 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoate (6.8 g, 20.34 mmol, 58.63%) was obtained after column chromatography on silica gel.

Step 4: 3-(Difluoromethylsulfonyl)-5-(trifluromethoxy)benzoic acid (INT-039)

[1396] ##STR00153##

[1397] To a stirred solution of methyl 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)benzoate (6.8 g, 20.34 mmol) in THF (80 mL)/water (20 mL) mixture at 0° C. LiOH monohydrate (1.146 g, 27.459 mmol) was added and the mixture was stirred overnight at r.t. THF was evaporated under reduced pressure, the water phase was acidified to pH=3 and extracted with MTBE (5×10 mL). Pure 3-(difluoromethylsulfonyl)-5-(trifluromethoxy)benzoic acid (3 g, 9.37 mmol, 34.12% yield) was obtained after recrystallization from 30% aqueous EtOH as white solid.

[1398] .sup.1H NMR (DMSO-d.sub.6, 400 MHz): δ=7.47 (t, 1H), 8.21 (s, 1H), 8.32 (s, 1H), 8.40 (s, 1H), 13.79 (s, 1H).

[1399] ESI mass [m/z]: 319.0 [M+H].sup.+

Synthesis of 6-[5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3-(dimethylamino)-1H-1,2,4-triazol-1-yl]-N-ethyl-N-methylnicotinamide (example I-232)

Step 1: Methyl 6-[5-{(1S)-1-[(tert-butoxycarbonyl)amino]ethyl}-3-(dimethylamino)-1H-1,2,4-triazol-1-yl]nicotinate

[1400] ##STR00154##

[1401] A solution of 2 g (10.57 mmol)N-(tert-butoxycarbonyl)-L-alanine in 25 ml dioxane under argon was treated with 4.42 g (11.63 mmol) bis(dimethylamino)(3-oxido-1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)methylium hexafluorophosphate (HATU) and 8.28 ml (47.50 mmol) N,N-diisopropylethylamine. The reaction mixture was stirred 10 minutes at room temperature and then 3.90 g (15.86 mmol) methyl N,N-dimethylcarbamimidothioate hydroiodide (1:1) was added and the mixture was stirred further 1 h at room temperature. Finally 2.65 g (15.86 mmol) methyl 6-hydrazinonicotinate, 25 ml dioxane and 6 ml acetic acid were added into the mixture and the stirring was kept overnight at room temperature. The mixture was diluted with ethyl acetate and washed with a saturated NaHCO.sub.3 solution and brine, dried over sodium sulfate and then the solvent was reduced under pressure. The residue was purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 3.51 g (purity: 99%; yield: 84%) of the title compound.

[1402] ESI mass [m/z]: 391.2 [M+H].sup.+

[1403] .sup.1H-NMR (400.2 MHz, d6-DMSO): δ=8.9645 (1.0); 8.9602 (0.9); 8.4646 (1.0); 8.4588 (0.9); 8.4429 (1.0); 8.4371 (1.0); 7.8941 (1.3); 7.8928 (1.4); 7.8725 (1.2); 7.8711 (1.3); 7.4274 (0.4); 7.4074 (0.4); 5.6538 (0.4); 5.6360 (0.6); 5.6179 (0.4); 3.9006 (8.0); 3.3283 (35.3); 2.9711 (16.0); 2.5253 (0.6); 2.5118 (12.2); 2.5075 (23.9); 2.5030 (31.2); 2.4984 (23.3); 2.4941 (11.6); 1.4158 (2.0); 1.3985 (1.9); 1.3342 (7.2); 1.0612 (0.4); 0.0080 (0.8); −0.0002 (25.1); −0.0084 (1.0)

Step 2: Methyl 6-{5-[(1S)-1-aminoethyl]-3-(dimethylamino)-1H-1,2,4-triazol-1-yl}nicotinate hydrochloride (1:1) (INT-037)

[1404] ##STR00155##

[1405] A solution of 2.52 g (6.45 mmol) methyl 6-[5-{(1S)-1-[(tert-butoxycarbonyl)amino]ethyl}-3-(dimethylamino)-1H-1,2,4-triazol-1-yl]nicotinate in 26 ml dioxane was treated with 4N HCl-dioxane solution (30.17 ml) and the mixture was stirred 18 h at room temperature. Then, the solvent was evaporated under reduced pressure to afford 8.58 g (purity: 100%) of the title compound which was used in the next step without further purification.

[1406] ESI mass [m/z]: 291.5 [M+H−HCl].sup.+

[1407] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ=8.9997 (1.4); 8.9987 (1.4); 8.9942 (1.4); 8.6467 (1.4); 8.5193 (1.0); 8.5136 (1.0); 8.4977 (1.1); 8.4919 (1.0); 7.9443 (1.4); 7.9227 (1.3); 5.3583 (0.9); 5.3413 (0.9); 3.9130 (8.3); 3.5687 (3.0); 3.3328 (17.5); 3.0343 (16.0); 2.6727 (0.4); 2.5262 (0.6); 2.5127 (10.1); 2.5084 (19.5); 2.5038 (25.0); 2.4993 (18.3); 2.4950 (9.0); 1.6214 (3.3); 1.6045 (3.2); 0.0078 (0.6); −0.0002 (16.9); −0.0086 (0.6)

Step 3: Methyl 6-[5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3-(dimethylamino)-1H-1,2,4-triazol-1-yl]nicotinate

[1408] ##STR00156##

[1409] To a solution of 2.13 g (6.50 mmol) methyl 6-{5-[(1S)-1-aminoethyl]-3-(dimethylamino)-1H-1,2,4-triazol-1-yl}nicotinate hydrochloride (1:1) in 90 ml dichloromethane were added 3.0 ml (17.36 mmol) N,N.diisopropylethylamine and then a solution of 1.2 g (4.33 mmol) 3,5-bis(trifluoromethyl)benzoyl chloride in 90 ml dichloromethane and then the reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane and washed with a 5% NaH.sub.2PO.sub.4 aqueous solution, a bicarbonate solution and brine. The organic phase was dried over sodium sulfate, and the solvent was reduced under pressure. The residue was crystallized in acetonitrile and the filtrate was reduced under pressure and purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 641 mg (purity: 98%; yield: 27%) of the title compound.

[1410] ESI mass [m/z]: 531.4 [M+H].sup.+

[1411] .sup.1H-NMR (400.2 MHz, d6-DMSO): δ=9.5405 (0.7); 9.5224 (0.8); 8.9423 (1.3); 8.9380 (1.3); 8.4684 (1.1); 8.4625 (1.4); 8.4548 (2.7); 8.4470 (1.3); 8.4411 (1.1); 8.3155 (0.9); 8.3093 (1.2); 7.9082 (1.3); 7.8879 (1.2); 7.8866 (1.2); 6.1599 (0.6); 6.1423 (0.9); 6.1247 (0.6); 3.8906 (8.3); 3.3249 (112.0); 2.9656 (16.0); 2.6800 (0.4); 2.6757 (0.9); 2.6712 (1.2); 2.6667 (0.9); 2.5247 (4.5); 2.5199 (7.0); 2.5112 (73.5); 2.5068 (144.4); 2.5023 (187.9); 2.4977 (137.7); 2.4933 (67.9); 2.3337 (0.9); 2.3291 (1.2); 2.3245 (0.8); 1.6462 (3.0); 1.6288 (3.0); 0.1460 (0.6); 0.0080 (5.0); −0.0002 (133.0); −0.0085 (4.8); −0.1496 (0.6)

Step 4: 6-[5-{(1S)-1-[3,5-Bis(trifluoromethyl)benzamido]ethyl}-3-(dimethylamino)-1H-1,2,4-triazol-1-yl]nicotinic acid

[1412] ##STR00157##

[1413] A solution of 508 mg (0.95 mmol) methyl 6-[5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3-(dimethylamino)-1H-1,2,4-triazol-1-yl]nicotinate in a mixture of 10.5 ml THF and 1 ml water was treated with 80 mg (1.91 mmol) lithium hydroxide monohydrate. The reaction mixture was stirred at room temperature overnight. The mixture was acidified with a 10% HCl aq. solution and was extracted with ethyl acetate. The combined organic layer were washed with brine, dried over sodium sulfate and the solvent was removed under reduced pressure to provide 457 mg (purity: 100%; yield: 93.0%) of the title compound.

[1414] ESI mass [m/z]: 517.0 [M+H].sup.+

[1415] .sup.1H-NMR (400.2 MHz, d6-DMSO): δ=9.5431 (0.7); 9.5253 (0.7); 8.9210 (1.2); 8.9194 (1.4); 8.9154 (1.3); 8.9136 (1.3); 8.4560 (2.5); 8.4439 (1.1); 8.4382 (1.0); 8.4224 (1.1); 8.4167 (1.1); 8.3071 (1.1); 7.8906 (1.3); 7.8891 (1.3); 7.8692 (1.2); 7.8676 (1.3); 6.1645 (0.5); 6.1470 (0.9); 6.1294 (0.5); 4.0384 (0.6); 4.0206 (0.6); 3.3305 (36.8); 2.9634 (16.0); 2.6723 (0.4); 2.6679 (0.3); 2.5259 (1.5); 2.5212 (2.3); 2.5125 (25.4); 2.5080 (50.6); 2.5034 (66.0); 2.4988 (47.4); 2.4942 (22.5); 2.3303 (0.4); 1.9895 (2.5); 1.9097 (0.8); 1.6479 (2.9); 1.6305 (2.9); 1.1935 (0.7); 1.1758 (1.4); 1.1580 (0.7); 0.0080 (1.9); 0.0059 (1.0); −0.0002 (51.5); −0.0085 (1.4)

Step 5: 6-[5-{(1S)-1-[3,5-Bis(trifluoromethyl)benzamido]ethyl}-3-(dimethylamino)-1H-1,2,4-triazol-1-yl]-N-ethyl-N-methylnicotinamide

[1416] ##STR00158##

[1417] A solution of 72 mg (0.13 mmol) 6-[5-{(1S)-1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3-(dimethylamino)-1H-1,2,4-triazol-1-yl]nicotinic acid in 2 ml dichloromethane was treated with 64 mg (0.17 mmol) bis(dimethylamino)(3-oxido-1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)methylium hexafluorophosphate (HATU) and 0.034 ml (0.19 mmol) N,N-diisopropylethylamine and then the mixture was stirred 10 minutes at room temperature. Finally, 0.018 ml (0.21 mmol)N-methylethylamine was added to the reaction and the mixture was stirred overnight at room temperature. The mixture was treated with a 5% aqueous NaH.sub.2PO.sub.4 solution and extracted several times with dichloromethane. The combined organic layers were washed with sodium bicarbonate and brine, dried and finally the solvent was reduced under pressure. The residue was purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 56 mg (purity: 99%; yield: 72%) of the title compound.

Synthesis of N-{(1S)-1-[1-{5-[(cyclopropylcarbonyl)(methyl)amino]pyridin-2-yl}-3-(dimethylamino)-1H-1,2,4-triazol-5-yl]ethyl}-3,5-bis(trifluoromethyl)benzamide Example I-269)

Step 1: N-(6-Chloropyridin-3-yl)-N-methylcyclopropanecarboxamide

[1418] ##STR00159##

[1419] To a solution of 3 g (21.0 mmol) 6-chloro-N-methylpyridin-3-amine in 55 ml dichloromethane and 11.0 ml (63.2 mmol) N,N.diisopropylethylamine was added a solution of 2.10 ml (23.1 mmol) cyclopropanecarbonyl chloride in 5 ml dichloromethane and the reaction mixture was stirred at room temperature for 1 h. The mixture was washed with an 5% NaH.sub.2PO.sub.4 aqueous solution, brine and then the organic phase was dried and evaporated under pressure. The residue was purified by flash chromatography using a mixture of cyclohexan/ethyl acetate as a eluent to provide 3.94 g (purity: 97%; yield: 86%) of the title compound.

[1420] ESI mass [m/z]: 211.1 [M+H].sup.+

Step 2: tert-Butyl 2-{5-[(cyclopropylcarbonyl)(methyl)amino]pyridin-2-yl}hydrazinecarboxy-late

[1421] ##STR00160##

[1422] To a solution of 3.94 g (18.7 mmol)N-(6-chloropyridin-3-yl)-N-methylcyclopropanecarboxamide in 101 ml toluene under argon were added 4.95 g (37.4 mmol) tert-butyl hydrazinecarboxylate, 685 mg (0.75 mmol) Pd.sub.2(dba).sub.3, 1.24 g (2.24 mmol) dppf and 12.2 mg (37.4 mmol) cesium carbonate and the reaction mixture was stirred at 100° C. overnight. The mixture was diluted with dichloromethane, filtered and evaporated under pressure. The residue was purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 2.96 g (purity: 96%, yield: 50%) of the title compound.

[1423] ESI mass [m/z]: 307.1 [M+H].sup.+

Step 3: N-(6-Hydrazinopyridin-3-yl)-N-methylcyclopropanecarboxamide

[1424] ##STR00161##

[1425] A solution of 3.1 g (10.1 mmol) tert-butyl 2-{5-[(cyclopropylcarbonyl)(methyl)amino]pyridin-2-yl}hydrazinecarboxylate in 71 ml dioxane was treated with 4N HCl-dioxane solution (25.2 ml) and the mixture was stirred 18 h at room temperature. Then, the solvent was evaporated under reduced pressure to afford 3.31 g (purity: 53%, yield:85%) of the title compound which was used in the next step without further purification.

[1426] ESI mass [m/z]: 207.1 [M+H−HCl]+

Step 4: tert-Butyl {(1S)-1-[1-{5-[(cyclopropylcarbonyl)(methyl)amino]pyridin-2-yl}-3-(dimethylamino)-1H-1,2,4-triazol-5-yl]ethyl}carbamate

[1427] ##STR00162##

[1428] A solution of 1.5 g (7.93 mmol)N-(tert-butoxycarbonyl)-L-alanine in 15 ml dioxane was treated with 3.32 g (8.72 mmol) bis(dimethylamino)(3-oxido-1H-[1,2,3]triazolo[4,5-b]pyridin-1-yl)methylium hexafluorophosphate (HATU) and 6.21 ml (35.66 mmol) N,N-diisopropylethylamine. The reaction mixture was stirred 10 minutes at room temperature and then 2.93 g (11.89 mmol) methyl N,N-dimethylcarbamimidothioate hydroiodide (1:1) was added and the mixture was stirred 1 h at room temperature. Finally 2.45 g (11.89 mmol)N-(6-hydrazinopyridin-3-yl)-N-methylcyclopropanecarboxamide, 15 ml dioxane and 4.6 ml acetic acid were added into the mixture and the stirring was kept further at room temperature overnight. The mixture was diluted with ethyl acetate and washed with a saturated NaHCO.sub.3 solution, brine, dried over sodium sulfate and then the solvent was reduced under pressure. The residue was purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 641 mg (purity: 96%, yield: 18%) of the title compound.

[1429] ESI mass [m/z]: 391.2 [M+H].sup.+

[1430] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ=8.5201 (0.8); 8.0420 (0.5); 8.0359 (0.5); 8.0202 (0.6); 8.0146 (0.5); 7.8328 (1.0); 7.8110 (0.8); 7.3962 (0.4); 7.3774 (0.4); 5.5726 (0.4); 5.5546 (0.5); 4.0561 (0.4); 4.0383 (1.1); 4.0205 (1.1); 4.0028 (0.4); 3.3296 (20.7); 3.2607 (1.1); 2.9526 (16.0); 2.5887 (0.4); 2.5116 (12.2); 2.5076 (21.8); 2.5032 (26.9); 2.4987 (19.6); 1.9894 (4.8); 1.4265 (2.4); 1.4093 (2.3); 1.3257 (8.5); 1.1933 (1.3); 1.1756 (2.6); 1.1578 (1.3); 1.0554 (0.5); 0.8429 (1.0); 0.8342 (1.6); 0.8233 (1.1); 0.6919 (0.7); 0.0077 (0.5); −0.0002 (8.3)

Step 5: N-(6-{5-[(1S)-1-Aminoethyl]-3-(dimethylamino)-1H-1,2,4-triazol-1-yl}pyridin-3-yl)-N-methylcyclopropanecarboxamide hydrochloride (1:1)

[1431] ##STR00163##

[1432] A solution of 611 mg (1.42 mmol) tert-butyl {(1S)-1-[1-{5-[(cyclopropylcarbonyl) (methyl)amino]pyridin-2-yl}-3-(dimethylamino)-1H-1,2,4-triazol-5-yl]ethyl}carbamate in 5.6 ml dioxane was treated with 4N HCl-dioxane solution (6.65 ml) and the mixture was stirred 18 h at room temperature. Then, the solvent was evaporated under reduced pressure to afford 573 mg (purity: 96%, yield: 100%) of the title compound which was used in the next step without further purification.

[1433] ESI mass [m/z]: 330.4[M+H−HCl].sup.+

[1434] .sup.1H-NMR (400.2 MHz, d6-DMSO): δ=8.5478 (1.7); 8.5421 (1.7); 8.1004 (0.4); 8.0941 (0.3); 8.0789 (0.4); 8.0728 (0.4); 7.8919 (0.9); 7.8700 (0.7); 5.3057 (0.3); 3.5681 (10.6); 3.3463 (62.6); 3.3089 (0.4); 3.2803 (0.8); 3.0193 (16.0); 2.9701 (0.8); 2.6761 (0.4); 2.6715 (0.6); 2.6669 (0.4); 2.6598 (0.5); 2.5250 (2.1); 2.5202 (3.2); 2.5116 (38.2); 2.5071 (75.5); 2.5025 (98.0); 2.4979 (70.6); 2.4934 (33.8); 2.3341 (0.4); 2.3294 (0.6); 2.3249 (0.4); 1.6129 (3.1); 1.5961 (2.9); 0.8650 (0.4); 0.8549 (0.9); 0.8474 (1.2); 0.8363 (1.0); 0.8288 (0.4); 0.7020 (0.5); 0.0079 (1.0); −0.0002 (31.1); −0.0086 (1.0)

Step 6:

N-{(1S)-1-[1-{5-[(Cyclopropylcarbonyl)(methyl)amino]pyridin-2-yl}-3-(dimethylamino)-1H-1,2,4-triazol-5-yl]ethyl}-3,5-bis(trifluoromethyl)benzamide

[1435] ##STR00164##

[1436] To a solution of 137 mg (0.37 mmol)N-(6-{5-[(1S)-1-aminoethyl]-3-(dimethylamino)-1H-1,2,4-triazol-1-yl}pyridin-3-yl)-N-methylcyclopropanecarboxamide hydrochloride (1:1) in 2 ml dichloromethane were added 0.17 ml (0.99 mmol) N,N.diisopropylethylamine and then a solution of 69 mg (0.25 mmol) 3,5-bis(trifluoromethyl)benzoyl chloride in 2 ml dichloromethane and the reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane and was washed with a 5% NaH.sub.2PO.sub.4 aqueous solution, bicarbonate solution and then brine. The organic phase was dried over sodium sulfate and the solvent was reduced under pressure. The residue was purified by reversed phase chromatography (H.sub.2O/acetonitrile) to provide 116 mg (purity: 97%; yield: 79%) of the title compound.

Intermediates: BOC-Protected Amines

[1437] Table A shows enantiomeric enriched intermediate compounds (Boc-INT) of general formula (a) according to the invention described in table A, wherein R.sup.1 is tert-butyloxycarbonyl (Boc), R.sup.3b is methyl, R.sup.3a is hydrogen and Y is a direct bond and wherein R.sup.4 and R.sup.5 have the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1), which are obtained according to or analogously to the preparation examples described above.

##STR00165##

TABLE-US-00001 TABLE A Example R4 R.sup.5 ee-Value Ret. Time ESI Mass (m/z).sup.1) Boc-INT-024 [00166] [00167]  100% 11.28 min 444.2 [M + H].sup.+ Boc-INT-027 [00168] [00169] 96.9% 11.20 min 444.1 [M + H].sup.+ Boc-INT-028 [00170] [00171]  100% 10.74 min 368.1 [M + H].sup.+ Boc-INT-029 [00172] [00173]  100% 10.51 min 454.1 [M + H].sup.+ Boc-INT-030 [00174] [00175]  100%  9.26 min 406.2 [M + H].sup.+ Boc-INT-031 [00176] [00177] 75.5% 11.17 min 360.2 [M + H].sup.+ Boc-INT-032 [00178] [00179]  100% 10.30 min 374.1 [M + H].sup.+ Boc-INT-033 [00180] [00181]  100% 12.09 min 406.1 [M + H].sup.+ Boc-INT-034 [00182] [00183]  100% 15.35 min 450.2 [M + H].sup.+ Boc-INT-035 [00184] [00185]  100% 15.24 min 436.4 [M + H].sup.+ Boc-INT-036 [00186] [00187]  100% 11.35 min 391.2 [M + H].sup.+ Boc-INT-038 [00188] [00189]  100% 12.25 min 439.2 [M + H].sup.+ .sup.1)The stated mass corresponds to the peak from the isotope pattern of the [M + H].sup.+ ion with the highest intensity.

Analytical Data of the Compounds

[1438] The determination of [M+H].sup.+ or [M−H].sup.− by LC-MS under acidic chromatographic conditions was done with 1 ml formic acid per liter acetonitrile and 0.9 ml formic acid per liter Millipore water as eluents. The column Zorbax Eclipse Plus C18 50 mm*2.1 mm was used. The temperature of the column oven was 55° C.

[1439] The enantomeric excesses of the intermediate compounds tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-[5-(morpholine-4-carbonyl)thiazol-2-yl]-1,2,4-triazol-3-yl]-N-methyl-carbamate, tert-butyl N-[5-[(1S)-1-(tert-butoxycarbonylamino)ethyl]-1-pyrimidin-2-yl-1,2,4-triazol-3-yl]-N-methyl-carbamate, tert-Butyl N-[(1S)-1-[5-(dimethylamino)-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl]carbamate, tert-butyl N-[(1S)-1-[5-(tert-butoxycarbonylamino)-2-(5-cyano-2-pyridyl)-1,2,4-triazol-3-yl]ethyl]carbamate, tert-butyl N-[(1S)-1-[5-[methoxy(methyl) amino]-2-pyrimidin-2-yl-1,2,4-triazol-3-yl]ethyl] carbamate, the intermediate compounds in table A and examples 1-031, 1-127, 1-134 were determined using chiral HPLC: Chiralcel OD-RH column (4.6 mm×150 mm×5 μm), room temperature, eluting with 0.1% phosphoric acid (A) and acetonitrile (B), gradient A:B 95/5 to 10/90, detecting at 210 nm. Analogously, the enantiomeric excess were determined for the examples given in Table 1: I-132 (ee-value: 92%; Rt=10.17 min); 1-137 (ee-value: 100%; Rt=7.70 min); 1-145 (ee-value: 100%; Rt=9.86 min); 1-169 (ee-value: 96%; Rt=8.90 min); 1-175 (ee-value: 81%; Rt=14.30 min); 1-176 (ee-value: 78%; Rt=12.87 min); 1-202 (ee-value: 100%; Rt=8.35 min); 1-206 (ee-value: 97%; Rt=12.90 min); 1-222 (ee-value: 100%; Rt=12.01 min).

[1440] The determination of the .sup.1H NMR data was effected with a Bruker Avance III 400 MHz equipped with a 1.7 mm TCI cryo probe, a Bruker Avance III 600 MHz equipped with a 5 mm multi-nuclear cryo probe or a Bruker Avance NEO 600 MHz equipped with a 5 mm TCI cryo probe with tetramethylsilane as reference (0.0) and the solvents CD.sub.3CN, CDCl.sub.3 or D.sub.6-DMSO.

[1441] The NMR data of selected examples are listed either in conventional form (S values, multiplet splitting, number of hydrogen atoms) or as NMR peak lists.

NMR Peak List Method

[1442] The .sup.1H NMR data of selected examples are stated in the form of .sup.1H NMR peak lists. For each signal peak, first the δ value in ppm and then the signal intensity in round brackets are listed. The pairs of δ value-signal intensity numbers for different signal peaks are listed with separation from one another by semicolons.

[1443] The peak list for one example therefore takes the form of:

δ.sub.1 (intensity.sub.1); δ.sub.2 (intensity.sub.2); . . . ; δ.sub.i (intensity.sub.i); . . . ; δ.sub.n (intensity.sub.n)

[1444] The intensity of sharp signals correlates with the height of the signals in a printed example of an NMR spectrum in cm and shows the true ratios of the signal intensities. In the case of broad signals, several peaks or the middle of the signal and the relative intensity thereof may be shown in comparison to the most intense signal in the spectrum.

[1445] For calibration of the chemical shift of .sup.1H NMR spectra, we use tetramethylsilane and/or the chemical shift of the solvent, particularly in the case of spectra which are measured in DMSO. Therefore, the tetramethylsilane peak may but need not occur in NMR peak lists.

[1446] The lists of the .sup.1H NMR peaks are similar to the conventional .sup.1H NMR printouts and thus usually contain all peaks listed in a conventional NMR interpretation.

[1447] In addition, like conventional .sup.1H NMR printouts, they may show solvent signals, signals of stereoisomers of the target compounds which are likewise provided by the invention, and/or peaks of impurities.

[1448] In the reporting of compound signals within the delta range of solvents and/or water, our lists of .sup.1H NMR peaks show the standard solvent peaks, for example peaks of DMSO in DMSO-D.sub.6 and the peak of water, which usually have a high intensity on average.

[1449] The peaks of stereoisomers of the target compounds and/or peaks of impurities usually have a lower intensity on average than the peaks of the target compounds (for example with a purity of >90%).

[1450] Such stereoisomers and/or impurities may be typical of the particular preparation process. Their peaks can thus help in identifying reproduction of our preparation process with reference to “by-product fingerprints”.

[1451] A person skilled in the art calculating the peaks of the target compounds by known methods (MestreC, ACD simulation, but also with empirically evaluated expected values) can, if required, isolate the peaks of the target compounds, optionally using additional intensity filters. This isolation would be similar to the peak picking in question in conventional .sup.1H NMR interpretation.

[1452] Further details of .sup.1H NMR peak lists can be found in the Research Disclosure Database Number 564025.

[1453] The compounds according to the invention described in table 1 below are likewise preferred compounds of the formula (I), wherein R.sup.1 is hydrogen, R.sup.3b is methyl, R.sup.3a is hydrogen, X is oxygen and Y is a direct bond which are obtained according to or analogously to the preparation examples described above.

##STR00190##

TABLE-US-00002 TABLE 1 Exam- ESI mass ple Structure.sup.3) NMR Peaklist.sup.1) [m/z].sup.2) I-001 [00191] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO, ppm): δ = 9.9040 (1.2); 9.4253 (0.5); 9.4078 (0.5); 8.9559 (2.6); 8.9437 (2.7); 8.1409 (0.9); 8.0909 (0.9); 8.0608 (0.8); 7.5881 (0.7); 7.5760 (1.3); 7.5639 (0.7); 5.9945 (0.4); 5.9772 (0.6); 5.9598 (0.4); 3.3216 (13.8); 2.5246 (0.8); 2.5111 (14.8); 2.5068 (30.1); 2.5023 (39.8); 2.4977 (28.9); 2.4933 (14.0); 1.6393 (2.0); 1.6219 (2.1); 1.4648 (0.9); 1.4280 (16.0); 1.3978 (0.6); 0.0080 (1.0); −0.0002 (30.1); −0.0085 (1.1). 512.2 [M + H].sup.+ I-002 [00192] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.9597 (1.3); 9.4565 (0.6); 9.4394 (0.6); 8.6066 (1.0); 8.6053 (1.1); 8.6003 (1.1); 8.5989 (1.0); 8.2971 (0.8); 8.2933 (1.4); 8.2895 (0.9); 8.1982 (0.9); 8.1944 (1.0); 8.1912 (1.5); 8.1859 (0.9); 8.1764 (0.8); 8.1699 (0.8); 8.1471 (1.0); 8.1428 (1.2); 8.1383 (0.7); 7.8087 (1.1); 7.8074 (1.0); 7.7867 (1.0); 7.7854 (1.0); 5.9913 (0.4); 5.9742 (0.6); 5.9569 (0.4); 5.7562 (5.8); 3.3328 (75.4); 3.3203 (7.0); 3.1753 (1.6); 3.1621 (1.6); 2.6717 (0.4); 2.5251 (1.2); 2.5116 (23.5); 2.5072 (45.3); 2.5027 (57.1); 2.4982 (40.7); 2.4937 (19.6); 2.3295 (0.3); 1.6306 (2.0); 1.6131 (2.0); 1.4326 (16.0); −0.0002 (0.6) 499.1 [M − isoButen].sup.+ I-003 [00193] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.9516 (1.2); 9.4034 (0.5); 9.3864 (0.6); 8.5937 (1.0); 8.5883 (1.0); 8.5873 (1.0); 8.1906 (0.7); 8.1842 (0.7); 8.1687 (0.8); 8.1622 (0.8); 8.1531 (1.0); 8.0996 (0.9); 8.0699 (0.9); 7.8018 (1.0); 7.8008 (1.0); 7.7800 (0.9); 7.7788 (1.0); 5.9753 (0.4); 5.9581 (0.6); 5.9408 (0.4); 5.7569 (1.4); 4.1056 (0.4); 4.0925 (0.4); 3.3307 (36.2); 3.1758 (2.5); 3.1627 (2.4); 2.5255 (0.8); 2.5207 (1.3); 2.5121 (15.2); 2.5076 (30.4); 2.5031 (39.2); 2.4985 (28.0); 2.4940 (13.4); 1.6262 (2.0); 1.6088 (2.0); 1.4311 (16.0); −0.0002 (0.4) 545.3 [M + H].sup.+ I-004 [00194] .sup.1H-NMR (400 MHz, d.sub.6-DMSO, ppm): δ = 9.3548 (1.1); 9.3368 (1.0); 8.8619 (4.0); 8.8498 (4.1); 8.3485 (0.4); 8.3365 (0.4); 8.1819 (1.9); 8.1365 (2.0); 8.0652 (1.8); 7.4487 (1.1); 7.4366 (2.0); 7.4245 (1.0); 6.0247 (0.7); 6.0071 (1.2); 5.9896 (0.8); 4.6986 (0.3); 4.6863 (0.3); 4.6771 (0.3); 4.6316 (0.4); 4.5829 (0.4); 4.5729 (0.4); 4.5594 (0.4); 4.5410 (0.4); 4.5155 (0.4); 4.4724 (0.4); 4.4552 (0.4); 4.4369 (0.4); 4.4244 (0.4); 4.4060 (0.4); 4.3866 (0.3); 3.6474 (0.5); 3.5686 (16.0); 2.8920 (1.8); 2.7326 (1.5); 2.7316 (1.4); 2.6774 (0.4); 2.6728 (0.6); 2.6683 (0.4); 2.5431 (0.4); 2.5263 (1.9); 2.5128 (36.1); 2.5084 (70.8); 2.5039 (91.3); 2.4993 412.1 [M − HCl].sup.+ (67.1); 2.4950 (33.4); 2.3352 (0.4); 2.3307 (0.6); 2.3262 (0.4); 1.5960 (4.2); 1.5787 (4.2); 1.5093 (0.4); 1.4919 (0.4); 0.0080 (2.0); −0.0002 (56.4); −0.0085 (2.3) I-005 [00195] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.3491 (4.0); 9.3373 (4.2); 8.5220 (6.8); 8.5211 (6.7); 8.5176 (7.0); 8.5167 (6.4); 8.3231 (5.7); 8.3206 (10.2); 8.3180 (5.7); 8.2195 (5.6); 8.2166 (8.0); 8.2137 (5.5); 8.1387 (5.8); 8.1358 (8.6); 8.1328 (5.0); 8.1024 (5.5); 8.0980 (5.2); 8.0878 (5.8); 8.0834 (5.7); 7.7024 (7.4); 7.7015 (7.0); 7.6878 (7.1); 7.6868 (6.7); 6.0264 (0.6); 6.0149 (3.0); 6.0032 (4.8); 5.9915 (3.1); 5.9799 (0.6); 5.7800 (12.2); 5.7521 (1.7); 3.3232 (46.4); 3.3058 (281.5); 3.2824 (0.4); 3.1733 (0.3); 2.6184 (0.9); 2.6154 (1.8); 2.6124 (2.5); 2.6093 (1.8); 2.6063 (0.8); 2.5214 (6.7); 2.5183 (8.7); 2.5151 (10.2); 2.5065 (145.2); 2.5034 (291.9); 2.5003 (393.4); 2.4973 (283.2); 2.4943 (131.6); 2.3904 (0.8); 455.1 [M + H].sup.+ 2.3874 (1.8); 2.3843 (2.4); 2.3812 (1.7); 2.3782 (0.8); 1.5848 (16.0); 1.5733 (16.0); 0.0053 (1.7); −0.0001 (44.0); −0.0057 (1.3) I-006 [00196] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3376 (2.9); 9.3201 (3.0); 8.5158 (5.5); 8.5097 (5.6); 8.1910 (5.4); 8.1414 (5.4); 8.1077 (3.3); 8.1013 (3.2); 8.0857 (3.7); 8.0792 (3.9); 8.0681 (5.2); 7.7040 (5.6); 7.6820 (5.1); 6.0224 (0.4); 6.0051 (2.1); 5.9877 (3.4); 5.9703 (2.2); 5.9528 (0.5); 5.7573 (16.0); 4.0982 (0.4); 3.7817 (5.0); 3.5612 (0.8); 3.5314 (0.6); 3.5100 (0.6); 3.5038 (0.6); 3.4939 (0.6); 3.4745 (0.5); 3.4621 (0.5); 3.4504 (0.4); 3.1690 (3.8); 2.6775 (0.6); 2.6731 (0.9); 2.6687 (0.6); 2.5264 (1.8); 2.5126 (74.2); 2.5086 (150.3); 2.5042 (197.0); 2.4997 (147.2); 2.4955 (76.8); 2.3913 (0.5); 2.3353 (1.1); 2.3309 (1.4); 2.3266 (1.1); 1.5867 (11.8); 1.5694 (12.0); 1.2340 (0.4); −0.0003 (1.6) 445.1 [M + H].sup.+ I-007 [00197] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.4837 (3.5); 9.4721 (3.4); 8.8573 (5.6); 8.8508 (5.5); 8.4734 (16.0); 8.3054 (7.9); 7.4313 (2.7); 7.2051 (0.6); 7.1201 (0.7); 7.0350 (0.6); 6.0520 (1.6); 6.0406 (2.2); 6.0292 (1.6); 5.7257 (0.5); 5.6841 (0.4); 3.6473 (0.3); 3.5034 (0.5); 3.4955 (0.5); 3.4891 (0.4); 3.4793 (0.5); 3.4725 (0.6); 3.4635 (0.6); 3.4557 (0.6); 3.4536 (0.6); 3.3904 (5.2); 3.3534 (17.4); 3.1693 (0.7); 2.6193 (1.2); 2.6164 (2.3); 2.6134 (3.1); 2.6104 (2.2); 2.6074 (1.0); 2.5224 (8.9); 2.5193 (11.7); 2.5161 (14.4); 2.5073 (217.0); 2.5044 (420.5); 2.5014 (557.9); 2.4984 (411.1); 2.4954 (200.7); 2.3913 (1.2); 446.2 [M + H].sup.+ 2.3884 (2.3); 2.3854 (3.1); 2.3823 (2.2); 2.3794 (1.1); 1.9086 (0.6); 1.6141 (10.7); 1.6028 (10.2); 1.2353 (0.6); 0.0053 (1.8); −0.0001 (47.8); −0.0057 (1.5) I-008 [00198] .sup.1H-NMR (400 MHz, d.sub.6-DMSO, ppm): δ = 3.5682 (16.0); 3.3248 (1.4); 2.5117 (6.8); 2.5074 (13.7); 2.5028 (18.0); 2.4983 (13.4); 2.4939 (6.8); 1.5995 (0.4); 1.5824(0.4); 1.2892(0.6); 1.2725(0.7); 1.2663 (0.8); 1.2591 (0.4); 1.2499 (0.7); −0.0002 (9.9): −0.0085 (0.4). 422.1 [M + H].sup.+ I-009 [00199] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6183 (0.5); 9.6006 (0.5); 8.9926 (2.6); 8.9804 (2.7); 8.4547 (1.8); 8.3216 (0.8); 7.6303 (0.7); 7.6182 (1.3); 7.6060 (0.7); 6.0646 (0.4); 6.0469 (0.6); 6.0293 (0.4); 5.7568 (2.2); 3.3346 (54.4); 3.2143 (7.0); 2.5263 (0.7); 2.5127 (14.4); 2.5084 (28.8); 2.5038 (37.0); 2.4993 (26.5); 2.4948 (12.8); 1.6756 (2.0); 1.6582 (2.0); 1.5031 (0.4); 1.3216 (16.0); −0.0002 (0.4) 561.1 [M + H].sup.+ I-010 [00200] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.3323 (3.0); 9.3962 (1.4); 9.3792 (1.4); 8.5911 (2.5); 8.5852 (2.6); 8.1943 (1.6); 8.1878 (1.5); 8.1725 (1.7); 8.1659 (1.7); 8.1421 (2.6); 8.0864 (2.6); 8.0684 (2.4); 7.7959 (2.6); 7.7738 (2.3); 5.9673 (1.0); 5.9501 (1.5); 5.9329 (1.0); 5.7568 (4.4); 4.1058 (0.5); 4.0926 (0.5); 3.6448 (16.0); 3.3308 (75.9); 3.1759 (2.6); 3.1628 (2.6); 2.6765 (0.4); 2.6724 (0.6); 2.6678 (0.4); 2.5076 (74.1); 2.5032 (94.4); 2.4987 (69.4); 2.3344 (0.4); 2.3301 (0.6); 2.3255 (0.4); 1.6324 (5.2); 1.6150 (5.2); −0.0002 (5.6) 503.1 [M + H].sup.+ I-011 [00201] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.6310 (1.2); 9.3851 (3.1); 9.3685 (3.2); 8.5918 (5.9); 8.5856 (5.9); 8.1953 (3.5); 8.1889 (3.3); 8.1734 (3.9); 8.1670 (3.8); 8.1478 (5.8); 8.0923 (5.8); 8.0705 (5.4); 7.8092 (5.6); 7.7873 (5.0); 5.9875 (0.5); 5.9703 (2.2); 5.9532 (3.5); 5.9361 (2.2); 5.9189 (0.5); 5.7569 (12.2); 4.1184 (0.8); 4.1055 (2.5); 4.0924 (2.5); 4.0791 (0.9); 3.3307 (118.0); 3.1759 (16.0); 3.1628 (15.6); 2.6766 (0.8); 2.6722 (1.1); 2.6679 (0.8); 2.5255 (3.8); 2.5077 (156.8); 2.5033 (198.8); 2.4988 (144.2); 2.3344 (0.9); 2.3301 (1.2); 2.3255 (0.9); 2.0560 (4.1); 1.6366 (12.2); 1.6193 (12.2); 1.4313 (0.4); 1.2341 (0.5); −0.0002 (2.1) 487.1 [M + H].sup.+ I-012 [00202] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.5593 (6.0); 9.4902 (2.4); 9.4734 (2.5); 8.6470 (4.4); 8.6459 (4.4); 8.6406 (4.5); 8.6395 (4.3); 8.3155 (0.3); 8.3004 (3.4); 8.2967 (6.0); 8.2929 (3.5); 8.2263 (3.1); 8.2199 (2.8); 8.2045 (3.4); 8.1979 (3.7); 8.1935 (3.4); 8.1890 (5.1); 8.1850 (3.5); 8.1539 (3.9); 8.1497 (5.5); 8.1451 (2.9); 7.8360 (4.6); 7.8142 (4.2); 6.0317 (0.3); 6.0143 (1.6); 5.9970 (2.6); 5.9797 (1.7); 5.9622 (0.3); 5.7561 (16.0); 4.1196 (0.5); 4.1064 (1.4); 4.0933 (1.4); 4.0802 (0.5); 3.3326 (186.2); 3.3234 (32.5); 3.1753 (6.9); 3.1622 (6.7); 2.6763 (0.8); 2.6717 (1.0); 2.6672 (0.8); 2.5250 (3.8); 2.5116 (72.4); 2.5073 (140.4); 2.5028 (178.2); 2.4983 (127.1); 2.4939 (61.2); 2.3341 (0.8); 2.3295 (1.0); 2.3252 (0.8); 1.6534 (8.6); 1.6360 (8.6); 1.5904 (2.2); 1.5774 (5.1); 1.5694 (5.7); 1.5573 (2.9); 1.3803 (3.0); 557.1 [M + H].sup.+ 1.3681 (5.6); 1.3606 (5.7); 1.3470 (2.2); −0.0002 (1.7) I-013 [00203] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 8.5997 (0.5); 8.5955 (0.5); 8.2970 (0.4); 8.2945 (0.7); 8.2920 (0.4); 8.1940 (0.4); 8.1896 (0.4); 8.1870 (0.4); 8.1840 (0.6); 8.1811 (0.4); 8.1795 (0.4); 8.1751 (0.4); 8.1427 (0.4); 8.1398 (0.6); 8.1368 (0.3); 7.8004 (0.5); 7.7859 (0.5); 5.9716 (0.3); 3.3223 (3.4); 3.3079 (36.9); 3.0733 (2.9); 3.0619 (2.8); 2.6156 (0.3); 2.6126 (0.4); 2.5216 (1.0); 2.5185 (1.3); 2.5154 (1.3); 2.5066 (25.0); 2.5036 (52.2); 2.5006 (71.5); 2.4975 (52.4); 2.4945 (24.9); 2.3845 (0.4); 1.6414 (1.1); 1.6298 (1.1); 1.2004 (8.0); 1.1883 (16.0); 1.1762 (7.8); 0.7934 (1.1); 0.7829 (1.5); −0.0001 (7.7) 523.1 [M + H].sup.+ I-014 [00204] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.5523 (4.6); 9.4356 (2.2); 9.4186 (2.2); 8.6328 (4.1); 8.6273 (4.2); 8.2176 (2.8); 8.2111 (2.6); 8.1957 (3.1); 8.1892 (3.1); 8.1531 (4.0); 8.1001 (4.0); 8.0754 (3.7); 7.8278 (4.4); 7.8060 (4.0); 6.0139 (0.3); 5.9966 (1.6); 5.9794 (2.5); 5.9621 (1.6); 5.7568 (6.1); 4.1193 (0.8); 4.1062 (2.4); 4.0930 (2.5); 4.0800 (0.8); 3.3315 (129.4); 3.1757 (16.0); 3.1626 (15.7); 2.6766 (0.7); 2.6720 (0.9); 2.6675 (0.7); 2.5254 (3.2); 2.5120 (62.6); 2.5076 (122.7); 2.5031 (156.1); 2.4985 (111.1); 2.4941 (53.0); 2.3344 (0.7); 2.3299 (0.9); 2.3253 (0.6); 1.6501 (8.4); 1.6327 (8.4); 1.5907 (2.2); 1.5777 (5.0); 1.5698 (5.5); 1.5576 (2.8); 1.3804 (2.9); 1.3681 (5.3); 1.3605 (5.4); 1.3469 (2.1); −0.0002 (1.7) 549.1 [M + H].sup.+ I-015 [00205] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.9181 (1.3); 9.3849 (2.2); 9.3681 (2.2); 8.5886 (4.0); 8.5832 (4.0); 8.5822 (3.9); 8.1935 (2.7); 8.1870 (2.5); 8.1716 (3.0); 8.1651 (3.0); 8.1512 (4.0); 8.0959 (3.9); 8.0715 (3.7); 7.7979 (4.0); 7.7759 (3.6); 5.9931 (0.3); 5.9758 (1.5); 5.9587 (2.3); 5.9416 (1.5); 5.9242 (0.3); 5.7568 (8.7); 4.1190 (0.9); 4.1059 (2.8); 4.0927 (2.8); 4.0797 (1.0); 3.3315 (138.5); 3.1758 (16.0); 3.1627 (15.6); 2.6767 (0.7); 2.6722 (0.9); 2.6676 (0.7); 2.5255 (3.4); 2.5119 (62.6); 2.5077 (121.5); 2.5032 (154.8); 2.4986 (111.1); 2.4943 (54.0); 2.3344 (0.6); 2.3300 (0.9); 2.3255 (0.6); 1.8973 (0.5); 1.6410 (8.1); 1.6236 (8.1); 0.7974 (9.6); 0.7819 (10.5); −0.0002 (1.8) 513.1 [M + H].sup.+ I-016 [00206] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 11.1330 (1.6); 9.3925 (2.5); 9.3758 (2.5); 8.6051 (4.5); 8.5993 (4.6); 8.3162 (0.3); 8.2109 (2.8); 8.2045 (2.7); 8.1890 (3.2); 8.1825 (3.2); 8.1449 (4.9); 8.0885 (4.9); 8.0718 (4.6); 7.8249 (3.9); 7.8030 (3.6); 5.9848 (0.4); 5.9674 (1.9); 5.9503 (2.9); 5.9332 (1.9); 5.9160 (0.4); 5.7567 (16.0); 4.1204 (0.5); 4.1073 (1.6); 4.0942 (1.6); 4.0812 (0.6); 3.5521 (1.1); 3.5278 (1.1); 3.3339 (289.5); 3.1759 (9.2); 3.1627 (8.8); 2.6768 (0.9); 2.6723 (1.3); 2.6677 (0.9); 2.5257 (4.2); 2.5122 (82.7); 2.5078 (164.8); 2.5033 (212.8); 2.4987 (153.3); 2.4943 (74.3); 2.3347 (0.9); 2.3300 (1.2); 2.3256 (0.9); 1.6442 (10.2); 1.6268 (10.2); −0.0002 (2.1) 555.1 [M + H].sup.+ I-017 [00207] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4423 (0.4); 9.4255 (0.5); 8.6056 (1.3); 8.6001 (1.3); 8.3160 (16.0); 8.2904 (1.8); 8.2868 (1.1); 8.2041 (0.8); 8.1976 (0.8); 8.1822 (2.4); 8.1782 (1.5); 8.1760 (1.4); 8.1496 (1.1); 8.1454 (1.6); 8.1411 (0.9); 7.8178 (1.2); 7.7955 (1.1); 5.9849 (0.4); 5.9685 (0.5); 5.9517 (0.4); 5.7562 (6.3); 3.3361 (48.9); 3.3234 (11.8); 3.3129 (4.8); 3.1677 (1.3); 2.6717 (0.4); 2.6675 (0.3); 2.5073 (56.6); 2.5029 (71.4); 2.4985 (53.0); 2.3295 (0.4); 2.3254 (0.3); 2.0546 (1.0); 1.6400 (2.7); 1.6226 (2.7); −0.0002 (0.5) 497.1 [M + H].sup.+ I-018 [00208] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 11.2326 (0.6); 9.3981 (1.4); 9.3814 (1.6); 9.3708 (0.7); 8.6019 (2.6); 8.5969 (3.3); 8.2088 (1.2); 8.2027 (1.4); 8.1870 (1.4); 8.1809 (1.6); 8.1510 (2.7); 8.0951 (2.7); 8.0720 (3.2); 7.8144 (2.8); 7.7925 (2.5); 5.9796 (0.9); 5.9624 (1.3); 5.9562 (0.8); 5.9453 (0.9); 5.7569 (16.0); 4.1054 (0.8); 4.0923 (0.9); 3.3303 (119.9); 3.1757 (5.6); 3.1626 (5.4); 2.8335 (0.3); 2.6765 (0.7); 2.6720 (1.0); 2.6675 (0.7); 2.6630 (0.4); 2.5254 (3.4); 2.5206 (5.5); 2.5119 (61.8); 2.5076 (122.0); 2.5031 (156.6); 2.4985 (112.3); 2.4941 (54.1); 2.3344 (0.6); 2.3298 (0.9); 2.3254 (0.6); 2.0257 (0.6); 2.0056 (1.2); 1.9888 (1.1); 1.9792 (1.2); 1.9587 (0.6); 1.6455 (6.5); 1.6281 (6.4); 1.2346 (0.4): −0.0002 (2.0) 549.1 [M + H].sup.+ I-019 [00209] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 11.1079 (1.4); 9.4730 (1.1); 9.4649 (1.3); 9.4563 (1.3); 9.4481 (1.2); 8.9810 (5.1); 8.9781 (5.2); 8.9689 (5.3); 8.9660 (5.2); 8.2691 (3.1); 8.2648 (3.2); 8.2609 (1.6); 8.1721 (2.8); 8.1678 (2.8); 8.1629 (1.6); 8.1415 (3.4); 7.6171 (1.4); 7.6147 (1.4); 7.6050 (2.6); 7.6026 (2.6); 7.5929 (1.4); 7.5905 (1.3); 6.0132 (1.1); 5.9958 (1.8); 5.9789 (1.2); 5.7565 (16.0); 4.6982 (0.5); 3.3342 (104.1); 3.3193 (20.8); 3.1755 (1.2); 3.1624 (1.2); 2.6767 (0.6); 2.6722 (0.7); 2.5076 (101.7); 2.5033 (127.8); 2.4988 (94.1); 2.3343 (0.6); 2.3301 (0.7); 2.3255 (0.5); 1.6658 (6.6); 1.6484 (6.7); 1.5961 (8.7); 1.5794 (8.6); −0.0002 (1.2) 512.1 [M + H].sup.+ I-020 [00210] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.5453 (4.0); 9.5069 (1.8); 9.4895 (1.8); 8.9958 (7.1); 8.9837 (7.3); 8.2743 (2.4); 8.2708 (4.3); 8.2671 (2.8); 8.1790 (2.2); 8.1745 (3.8); 8.1707 (2.7); 8.1462 (2.8); 8.1419 (3.9); 8.1376 (2.1); 7.6394 (1.9); 7.6273 (3.5); 7.6151 (1.8); 6.0368 (1.1); 6.0194 (1.8); 6.0020 (1.1); 5.7563 (16.0); 4.1053 (0.3); 4.0921 (0.4); 3.3749 (0.4); 3.3620 (0.7); 3.3316 (67.2); 3.3192 (20.5); 3.1754 (1.9); 3.1623 (1.8); 2.6764 (0.5); 2.6720 (0.7); 2.6674 (0.5); 2.5251 (2.8); 2.5073 (95.6); 2.5029 (121.4); 2.4985 (90.0); 2.3341 (0.5); 2.3298 (0.7); 2.3253 (0.5); 1.6669 (6.4); 1.6495 (6.4); 1.5895 (1.4); 1.5779 (3.1); 1.5694(3.9); 1.5578 (1.9); 524.1 [M + H].sup.+ 1.3844 (2.0); 1.3727 (3.9); 1.3650 (3.9); 1.3523 (1.5); −0.0002 (1.2) I-021 [00211] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 11.2094 (0.6); 9.4583 (1.2); 9.4418 (1.2); 8.9706 (4.8); 8.9691 (4.7); 8.9586 (5.0); 8.2613 (3.1); 8.1655 (2.8); 8.1621 (2.9); 8.1422 (2.7); 8.1383 (3.8); 7.6054 (1.5); 7.5934 (2.8); 7.5813 (1.4); 6.0092 (0.9); 5.9935 (1.4); 5.9765 (0.9); 5.7564 (16.0); 4.1063 (0.3); 4.0933 (0.3); 3.3330 (89.1); 3.3180 (20.2); 3.1754 (2.0); 3.1623 (1.9); 2.6764 (0.6); 2.6720 (0.8); 2.6676 (0.6); 2.5075 (112.0); 2.5031 (142.1); 2.4987 (104.6); 2.3343 (0.6); 2.3299 (0.8); 2.3253 (0.6); 2.0281 (0.6); 2.0033 (1.1); 1.9927 (1.0); 1.9807 (1.3); 1.6630 (5.9); 1.6457 (5.9); −0.0002 (1.5) 526.1 [M + H].sup.+ I-022 [00212] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO, ppm): δ = 11.7003 (0.4); 10.5420 (3.1); 9.4658 (1.3); 9.4485 (1.3); 8.9917 (6.4); 8.9795 (6.6); 8.1447 (2.3); 8.0962 (2.4); 8.0704 (2.2); 7.6351 (1.7); 7.6230 (3.2); 7.6108 (1.6); 6.0247 (1.0); 6.0073 (1.5); 5.9899 (1.0); 5.7569 (0.5); 4.2608 (0.4); 3.7780 (0.3); 3.6476 (0.3); 3.3359 (23.8); 2.8917 (0.6); 2.7325 (0.5); 2.6767 (0.4); 2.6723 (0.6); 2.6679 (0.5); 2.5257 (1.8); 2.5209 (2.7); 2.5122 (35.5); 2.5078 (72.8); 2.5033 (96.9); 2.4988 (72.6); 2.4944 (37.0); 2.4250 (0.3); 2.3347 (0.4); 2.3300 (0.6); 2.3257 (0.4); 1.9894 (0.4); 1.9094 (16.0); 1.6628 (5.2); 1.6453 (5.2); 1.5892 (1.2); 1.5777 (2.5); 1.5670 (4.3); 1.5535 (6.2); 1.5454 (6.3); 514.1 [M + H].sup.+ 1.5335 (3.4); 1.4918 (0.4); 1.4184 (0.4); 1.3837 (1.7); 1.3763 (4.0); 1.3720 (3.3); 1.3646 (8.9); 1.3568 (6.2); 1.3520 (1.9); 1.3432 (2.3); 1.2342 (0.5); 1.1755 (0.4); 0.1459 (0.5); 0.0080 (3.4); −0.0002 (103.6); −0.0084 (4.5); −0.1495 (0.5). I-023 [00213] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 13.1206 (0.4); 11.7976 (0.4); 10.8800 (1.6); 9.4104 (2.6); 9.3935 (2.6); 9.0016 (0.6); 8.9894 (0.6); 8.9539 (10.6); 8.9418 (10.7); 8.8594 (0.5); 8.8475 (0.6); 8.2583 (0.7); 8.2203 (0.8); 8.1783 (0.4); 8.1370 (5.0); 8.0855 (5.1); 8.0655 (4.8); 7.5851 (2.8); 7.5730 (5.2); 7.5608 (2.6); 7.2144 (0.3); 6.0147 (0.4); 6.0068 (0.4); 5.9979 (1.8); 5.9806 (2.9); 5.9634 (1.8); 5.9461 (0.4); 5.7566 (16.0); 5.7443 (0.5); 4.2174 (0.5); 4.0108 (0.9); 3.3315 (152.7); 3.1758 (1.3); 3.1627 (1.3); 2.6765 (0.9); 2.6721 (1.2); 2.6679 (0.9); 2.5252 (4.0); 2.5075 (176.0); 2.5032 (223.6); 2.4989 (164.9); 2.3343 (1.0); 2.3301 (1.4); 2.3257 (1.0); 1.9097 (0.6); 480.2 [M + H].sup.+ 1.8472 (0.4); 1.6521 (10.0); 1.6348 (10.0); 1.6046 (0.7); 1.5941 (0.9); 1.5872 (0.7); 1.5777 (0.7); 1.5297 (1.2); 1.5126(1.1); 1.3513 (0.4); 1.2982 (0.3); 1.2590 (0.5); 1.2345 (0.9); 0.8918 (0.5); 0.8847 (0.7); 0.8650 (1.1); 0.8539 (1.0); 0.8346 (0.6); 0.7964 (10.6); 0.7810 (13.6); −0.0002 (2.3) I-024 [00214] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 11.0950 (0.7); 9.4161 (2.8); 9.3991 (2.8); 8.9577 (14.6); 8.9456 (15.0); 8.1352 (5.0); 8.0822 (5.0); 8.0664 (4.6); 7.5924 (3.9); 7.5803 (7.2); 7.5681 (3.8); 6.0119 (0.4); 5.9948 (2.0); 5.9775 (3.2); 5.9603 (2.0); 5.9433 (0.4); 5.7565 (16.0); 4.9328 (0.9); 4.7707 (0.9); 3.3372 (324.4); 3.1761 (1.2); 3.1629 (1.2); 2.6903 (0.5); 2.6815 (0.4); 2.6772 (0.8); 2.6727 (1.1); 2.6680 (0.8); 2.6636 (0.4); 2.5261 (3.5); 2.5213 (5.7); 2.5127 (67.2); 2.5082 (135.1); 2.5037 (175.5); 2.4991 (125.7); 2.4946 (60.4); 2.3395 (0.5); 2.3350 (0.9); 2.3305 (1.1); 2.3259 (0.9); 1.6532 (10.2); 1.6358 (10.2); 1.5505 (0.5); 1.5412 (0.7); 1.5250 (0.5); 498.2 [M + H].sup.+ 1.5108 (0.6); 1.4850 (0.7); 1.4709 (0.5); 1.4430 (0.6); 1.2539 (0.5); 1.2383 (1.3); 1.2221 (1.6); 1.2056(1.6); 1.1894 (1.3); 1.1729 (0.7); −0.0002 (1.9) I-025 [00215] 533.1 [M + H].sup.+ I-026 [00216] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5449 (0.8); 9.5271 (0.8); 8.6885 (1.5); 8.6832 (1.6); 8.2629 (1.0); 8.2564 (1.0); 8.2412 (2.2); 8.2381 (2.3); 8.2346 (2.4); 8.1597 (1.1); 8.1552 (1.9); 8.1509 (1.2); 8.1168 (1.3); 8.1127 (1.7); 8.1084 (1.0); 7.9674 (1.5); 7.9454 (1.4); 6.0185 (0.6); 6.0008 (0.9); 5.9831 (0.6); 5.7563 (11.5); 3.6401 (16.0); 3.3300 (76.3); 3.3208 (11.0); 3.1750 (0.7); 3.1619 (0.7); 2.6758 (0.4); 2.6713 (0.5); 2.6666 (0.4); 2.5248 (1.7); 2.5112 (33.7); 2.5069 (66.7); 2.5024 (85.6); 2.4978 (61.5); 2.4934 (29.8); 2.3337 (0.4); 2.3292 (0.5); 2.3248 (0.4); 1.6563 (3.0); 1.6389 (3.0); −0.0002 (1.0) 611.1 [M + H].sup.+ I-027 [00217] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.4695 (2.0); 9.4579 (2.1); 8.6538 (3.4); 8.6530 (3.2); 8.6496 (3.4); 8.6487 (3.0); 8.2478 (2.8); 8.2453 (5.0); 8.2427 (2.8); 8.2274 (2.6); 8.2231 (2.5); 8.2128 (2.8); 8.2085 (2.8); 8.1407 (1.6); 8.1374 (5.1); 8.1347 (7.9); 8.1322 (4.5); 8.1289 (1.3); 7.8809 (3.7); 7.8802 (3.4); 7.8664 (3.5); 7.8656 (3.1); 5.9792 (1.5); 5.9675 (2.3); 5.9559 (1.5); 5.7519 (13.9); 4.6872 (7.4); 3.3144 (23.8); 3.3057 (131.6); 3.1369 (16.0); 2.6184 (0.5); 2.6153 (1.0); 2.6123 (1.3); 2.6092 (1.0); 2.6063 (0.4); 2.5213 (3.7); 2.5182 (4.8); 2.5150 (5.8); 2.5064 (78.9); 2.5033 (158.2); 2.5003 (212.9); 2.4972 (152.9); 2.4942 (70.8); 2.3902 (0.4); 2.3873 (1.0); 2.3842 (1.3); 2.3812 (0.9); 2.3782 (0.4); 1.6531 (7.7); 1.6415 (7.7); 0.0053 (0.6); −0.0001 (15.3); −0.0057 (0.5) 532.0 [M + H].sup.+ I-028 [00218] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 12.6639 (2.2); 9.2674 (2.0); 9.2558 (2.0); 8.6416 (3.3); 8.6408 (3.2); 8.6373 (3.4); 8.6364 (3.1); 8.3199 (0.9); 8.3149 (0.7); 8.3126 (1.1); 8.3078 (0.8); 8.3046 (1.0); 8.2223 (2.6); 8.2180 (2.5); 8.2078 (2.8); 8.2034 (2.8); 8.1926 (5.7); 8.1894 (6.4); 8.1412 (1.7); 8.1380 (2.7); 8.1348 (1.3); 7.9841 (0.3); 7.9758 (1.7); 7.9721 (1.3); 7.9685 (1.4); 7.9672 (1.3); 7.9636 (1.5); 7.9606 (1.9); 7.9596 (1.8); 7.9516 (0.4); 7.9242 (1.3); 7.9205 (0.9); 7.9156 (1.1); 7.9130 (0.6); 7.9089 (0.7); 7.8685 (3.7); 7.8677 (3.5); 7.8540 (3.4); 7.8532 (3.2); 7.8021 (2.2); 7.7990 (4.6); 7.7958 (2.8); 7.7641 (11.5); 7.7609 (9.7); 5.9302 (1.5); 5.9186 (2.4); 5.9070 (1.5); 5.8954 (0.3); 4.6822 (7.4); 3.3057 (210.1); 3.2911 (0.5); 3.2821 (0.3); 3.1338 (16.0); 2.6185 (0.7); 2.6154 (1.5); 2.6124 (2.1); 2.6093 (1.5); 2.6062 (0.7); 489.9 [M + H].sup.+ 2.5214 (5.4); 2.5183 (6.9); 2.5152 (8.0); 2.5065 (122.6); 2.5034 (246.0); 2.5004 (330.6); 2.4973 (237.8); 2.4943 (110.4); 2.3905 (0.7); 2.3874 (1.5); 2.3843 (2.0); 2.3813 (1.4); 2.3783 (0.7); 2.0719 (0.6); 1.6287 (7.9); 1.6170 (7.9); 0.0053 (1.0); −0.0001 (26.2); −0.0057 (0.8) I-029 [00219] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.4181 (2.0); 9.4065 (2.1); 8.6401 (3.3); 8.6393 (3.2); 8.6358 (3.4); 8.6350 (3.1); 8.2177 (2.6); 8.2133 (2.5); 8.2031 (2.8); 8.1988 (2.8); 8.1000 (3.2); 8.0613 (2.9); 8.0412 (3.2); 7.8725 (3.7); 7.8717 (3.4); 7.8580 (3.4); 7.8572 (3.2); 5.9626 (1.5); 5.9510 (2.3); 5.9394 (1.5); 4.6884 (7.6); 3.3096 (30.6); 3.1350 (16.0); 2.5229 (0.6); 2.5198 (0.7); 2.5167 (0.7); 2.5080 (16.6); 2.5049 (35.6); 2.5018 (49.2); 2.4988 (35.8); 2.4958 (16.6); 2.0735 (1.4); 1.6520 (7.8); 1.6404 (7.8); −0.0001 (1.9) 522.1 [M + H].sup.+ I-030 [00220] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.5022 (2.0); 9.4906 (2.0); 9.1661 (2.9); 9.1630 (2.9); 9.1229 (2.5); 9.1208 (2.5); 8.6507 (3.2); 8.6499 (3.2); 8.6464 (3.4); 8.6455 (3.1); 8.4753 (2.8); 8.4721 (1.6); 8.2236 (2.6); 8.2193 (2.5); 8.2091 (2.8); 8.2048 (2.8); 7.8840 (3.6); 7.8832 (3.5); 7.8695 (3.4); 7.8687 (3.2); 5.9964 (1.5); 5.9848 (2.4); 5.9732 (1.5); 4.6911 (7.8); 3.3092 (56.3); 3.1360 (16.0); 2.6132 (0.4); 2.5223 (0.9); 2.5192 (1.1); 2.5161 (1.1); 2.5073 (24.1); 2.5043 (51.5); 2.5012 (71.3); 2.4982 (51.9); 2.4952? (24.3); 2.3852 (0.4); 2.0729 (0.9); 1.6638 (7.9); 1.6521 (7.9); −0.0001 (4.5). 489.2 [M + H].sup.+ I-031 [00221] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.3866 (4.4); 9.3752 (4.6); 9.0449 (6.6); 9.0410 (6.7); 8.6467 (7.0); 8.6426 (7.1); 8.4321 (4.8); 8.4280 (4.6); 8.4182 (5.0); 8.4141 (4.9); 8.2523 (4.6); 8.2480 (4.4); 8.2378 (5.1); 8.2335 (5.1): 8.0062 (7.7); 7.9918 (6.9); 7.9289 (5.3); 7.9263 (8.4); 7.9237 (5.4); 7.7735 (5.7); 7.7067 (5.8); 7.6888 (7.0); 7.6750 (6.8); 6.0195 (0.7); 6.0079 (3.0); 5.9964 (4.8); 5.9849 (3.1); 5.9732 (0.6); 3.9195 (1.0); 3.3268 (30.6); 2.8954 (1.0); 2.7367 (0.8); 2.6198 (0.4); 2.5288 (0.8); 2.5258 (1.0); 2.5227 (1.1); 2.5138 (20.0); 2.5108 (41.8); 2.5078 (57.4); 2.5048 (42.4); 2.5019 (20.2); 2.3917 (0.4); 1.7082 (15.9); 1.6966 (16.0); −0.0001 (3.4). 557.1 [M + H].sup.+ I-032 [00222] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.4517 (4.0); 9.4403 (4.1); 9.0463 (6.7); 9.0452 (6.7); 9.0423 (6.8); 9.0411 (6.4); 8.6496 (6.9); 8.6487 (6.8); 8.6453 (7.1); 8.6444 (6.5); 8.4340 (5.7); 8.4300 (5.4); 8.4201 (6.0); 8.4161 (6.0); 8.2509 (5.5); 8.2465 (5.2); 8.2364 (6.1); 8.2320 (6.1); 8.1301 (6.7); 8.1275 (4.2); 8.0653 (12.7); 8.0057 (7.7); 8.0048 (7.2); 7.9912 (6.9); 7.9903 (6.6); 7.6904 (7.1); 7.6892 (6.8); 7.6765 (7.0); 7.6753 (6.6); 6.0292 (0.6); 6.0176 (3.0); 6.0060 (4.8); 5.9944 (3.1); 5.9829 (0.6); 3.9176 (0.6); 3.3059 (719.0); 3.2893 (0.8); 3.2820 (0.8); 2.6186 (1.9); 2.6155 (4.0); 2.6125 (5.5); 2.6094 (3.9); 2.6064 (1.8); 2.5366 (0.8); 2.5215 (15.2); 2.5184 (19.7); 2.5153 (22.7); 2.5066 (314.7); 2.5036 (636.7); 2.5005 (860.8); 2.4974 (617.7); 2.4944 (284.0); 2.3905 (1.8); 2.3875 (3.8); 2.3844 (5.3); 2.3814 (3.7); 2.3783 (1.6); 1.7141 (16.0); 1.7025 (16.0); 1.6939 (0.6); 1.2345 (0.5); 0.9486 (0.5); 0.9377 (0.6); 0.0968 (0.3); 0.0053 (3.8); −0.0001 (96.2); −0.0057 (2.8); −0.1002 (0.3) 543.1 [M + H].sup.+ I-033 [00223] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5369 (3.9); 9.5255 (4.0); 9.1934 (6.1); 9.1902 (5.9); 9.1240 (5.2); 9.1219 (5.1); 9.0515 (6.4); 9.0505 (6.4); 9.0475 (6.5); 9.0465 (6.0); 8.6616 (6.6); 8.6609 (6.5); 8.6574 (6.8); 8.6566 (6.3); 8.5035 (5.7); 8.4391 (5.3); 8.4350 (5.0); 8.4252 (5.5); 8.4211 (5.4); 8.2577 (5.0); 8.2534 (4.8); 8.2432 (5.6); 8.2389 (5.5); 8.0192 (7.4); 8.0047 (6.6); 8.0039 (6.3); 7.6914 (6.8); 7.6905 (6.4); 7.6775 (6.6); 7.6765 (6.3); 6.0657 (0.6); 6.0542 (3.0); 6.0426 (4.8); 6.0311 (3.0); 6.0195 (0.6); 3.9177 (0.5); 3.3066 (245.3); 3.2829 (0.3); 2.6191 (0.8); 2.6161 (1.7); 2.6131 (2.3); 2.6100 (1.6); 2.6070 (0.7); 2.5221 (6.3); 2.5190 (8.1); 2.5158 (9.5); 2.5071 (138.4); 2.5041 (277.3); 2.5011 (373.0); 2.4980 (269.0); 2.4950 (125.4); 2.3911 (0.9); 2.3880 (1.7); 2.3850 (2.3); 2.3819 (1.6); 2.3789 (0.7); 1.8883 (0.3); 1.8766 (0.3); 1.7260 (16.0); 1.7144 (16.0); 0.0053 (1.0); −0.0001 (26.3); −0.0057 (0.8) 508.0 [M + H].sup.+ I-034 [00224] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.3501 (1.3); 9.3387 (1.4); 9.3190 (3.1); 9.3165 (3.0); 8.7830 (1.8); 8.7804 (1.9); 8.7788 (2.4); 8.7763 (2.2); 8.7582 (3.7); 8.7541 (2.6); 8.6721 (2.3); 8.6679 (2.3); 8.5585 (1.9); 8.2690 (1.8); 8.2647 (1.6); 8.2545 (2.0); 8.2502 (1.9); 8.0212 (2.5); 8.0067 (2.3); 7.8068 (14.0); 7.6530 (0.4); 7.3637 (1.0); 7.3605 (0.9); 6.0174 (1.0); 6.0059 (1.6); 5.9942 (1.0); 3.3061 (2015.4); 3.2825 (2.7); 2.6181 (5.7); 2.6151 (11.8); 2.6121 (16.0); 2.6090 (11.2); 2.6060 (5.0); 2.5361 (2.4); 2.5211 (44.4); 2.5180 (57.6); 2.5148 (66.8); 2.5062 (955.7); 2.5031 (1909.6); 2.5001 (2556.6); 2.4970 (1828.8); 2.4940 (841.4); 2.4049 (0.4); 2.4017 (0.4); 2.3901 (5.8); 2.3871 (11.8); 2.3840 (15.8); 2.3810 (11.0); 2.3779 (4.9); 2.0849 (0.6); 2.0716 (1.2); 1.7052 (5.3); 1.6935 (5.1); 1.6853 (0.4); 1.5086 (0.5); 1.2353 (1.0); 0.0967 (0.5); 0.0053 (5.7); −0.0001 475.1 [M + H].sup.+ (146.2); −0.0057 (4.3); −0.1000 (0.6) I-035 [00225] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5918 (1.1); 9.5810 (1.1); 9.3291 (3.5); 9.3267 (3.4); 8.7899 (2.0); 8.7873 (2.2); 8.7857 (2.8); 8.7832 (2.5); 8.7652 (4.1); 8.7611 (2.9); 8.6791 (2.6); 8.6782 (2.5); 8.6748 (2.6); 8.6739 (2.4); 8.2779 (2.0); 8.2736 (1.9); 8.2634 (2.2); 8.2591 (2.2); 8.0302 (2.9); 8.0294 (2.7); 8.0157 (2.6); 8.0148 (2.4); 7.9189 (1.3); 7.8468 (16.0); 6.0431 (0.7); 6.0318 (1.1); 6.0204 (0.7); 4.2860 (0.3); 3.8267 (0.4); 3.8156 (0.6); 3.8045 (0.4); 3.3070 (126.9); 2.6190 (0.4); 2.6160 (0.8); 2.6130 (1.1); 2.6099 (0.8); 2.6070 (0.3); 2.5220 (3.0); 2.5189 (4.0); 2.5157 (4.8); 2.5070 (65.1); 2.5040 (129.3); 2.5010 (173.2); 2.4979 (124.6); 2.4949 (57.8); 2.3910 (0.4); 2.3880 (0.8); 2.3849 (1.0); 2.3819 (0.7); 2.3788 (0.3); 1.7108 (6.2); 1.6992 (6.2); 1.2376 (5.3); 1.2264 (5.5); 1.2201 (7.1); 1.2090 (6.7); 0.0053 (0.5); −0.0001 (11.4); −0.0057 (0.4) 475.0 [M + H].sup.+ I-036 [00226] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.4929 (3.9); 9.4814 (4.0); 9.3207 (9.5); 9.3182 (9.4); 8.7827 (4.9); 8.7801 (5.6); 8.7786 (7.1); 8.7761 (6.7); 8.7582 (11.1); 8.7540 (8.0); 8.6688 (6.7); 8.6681 (6.4); 8.6645 (7.0); 8.2787 (6.8); 8.2637 (5.1); 8.2594 (4.9); 8.2492 (5.7); 8.2449 (5.7); 8.1676 (6.0); 8.1146 (6.5); 8.0226 (7.7); 8.0082 (6.9); 6.0588 (0.6); 6.0473 (2.9); 6.0357 (4.6); 6.0241 (2.9); 6.0125 (0.6); 3.3070 (261.3); 3.2831 (0.4); 2.6191 (0.8); 2.6162 (1.8); 2.6131 (2.5); 2.6101 (1.8); 2.6070 (0.9); 2.5222 (5.8); 2.5191 (6.9); 2.5160 (6.6); 2.5072 (133.8); 2.5042 (283.1); 2.5011 (390.3); 2.4981 (284.0); 2.4950 (133.3); 2.3911 (0.8); 2.3881 (1.7); 2.3851 (2.4); 2.3820 (1.7); 2.3791 (0.8); 1.7257 (15.9); 1.7141 (16.0); 0.0053 (0.8); −0.0001 (27.8); −0.0056 (0.9) 554.0 [M + H].sup.+ I-037 [00227] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.7335 (2.4); 9.7252 (2.5); 9.3307 (9.4); 9.3282 (9.3); 8.7888 (5.0); 8.7863 (5.7); 8.7847 (7.2); 8.7822 (6.8); 8.7649 (11.1); 8.7608 (7.9); 8.6805 (6.6); 8.6797 (6.5); 8.6762 (6.9); 8.6754 (6.4); 8.2747 (5.0); 8.2704 (4.8); 8.2602 (5.8); 8.2559 (5.8); 8.2151 (0.5); 8.2051 (9.0); 8.2034 (9.3); 8.1632 (8.7); 8.0331 (7.4); 8.0186 (6.6); 8.0178 (6.3); 6.0802 (1.3); 6.0693 (2.0); 6.0586 (1.5); 3.8313 (0.4); 3.3070 (270.7); 3.2807 (0.3); 2.6191 (0.8); 2.6162 (1.7); 2.6131 (2.4); 2.6100 (1.7); 2.6070 (0.8); 2.5222 (5.8); 2.5191 (7.0); 2.5160 (6.8); 2.5072 (134.8); 2.5042 (281.6); 2.5011 (385.6); 2.4981 (281.7); 2.4951 (133.6); 2.3912 (0.8); 2.3881 (1.8); 2.3851 (2.4); 2.3820 (1.7); 2.3790 (0.8); 1.7340 (15.9); 1.7224 (16.0); 1.2475 (3.1); 1.2364 (3.4); 1.2310 (4.8); 1.2198 (4.4); 0.0053 (0.8); −0.0001 (23.0); −0.0056 (0.8) 509.1 [M + H].sup.+ I-038 [00228] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5805 (3.8); 9.5688 (3.8); 9.3607 (0.8); 9.3269 (9.5); 9.3244 (9.2); 9.2038 (5.9); 9.2006 (5.7); 9.1257 (5.0); 9.1236 (4.9); 9.0620 (0.8); 9.0597 (0.8); 8.7837 (5.3); 8.7812 (5.8); 8.7796 (7.4); 8.7770 (6.9); 8.7673 (0.3); 8.7595 (11.1); 8.7554 (7.9); 8.6809 (6.8); 8.6799 (6.4); 8.6766 (6.9); 8.6757 (6.1); 8.5407 (0.8); 8.5241 (5.6); 8.5208 (3.2); 8.2701 (5.4); 8.2658 (5.1); 8.2556 (6.0); 8.2513 (5.9); 8.0358 (7.7); 8.0349 (7.0); 8.0213 (6.9); 8.0204 (6.3); 7.8994 (0.3); 6.2438 (0.4); 6.2232 (0.4); 6.0976 (0.6); 6.0861 (3.0); 6.0745 (4.8); 6.0629 (3.1); 6.0513 (0.6); 4.2769 (0.4); 3.8046 (0.4); 3.3068 (314.0); 3.2925 (0.9); 2.6190 (1.1); 2.6160 (2.2); 2.6129 (3.1); 2.6098 (2.2); 2.6068 (1.0); 2.5220 (7.9); 2.5188 (10.1); 2.5157 (11.5); 2.5070 (179.6); 2.5040 (364.0); 2.5009 (491.9); 2.4978 (353.2); 2.4948 (162.5); 2.3910 (1.1); 2.3879 (2.3); 2.3849 475.1 [M + H].sup.+ (3.1); 2.3818 (2.1); 2.3788 (1.0); 1.7398 (16.0); 1.7281 (16.0); 1.2443 (4.3); 1.2331 (5.1); 1.2288 (5.4); 1.2176 (4.6); 0.0053 (1.6); −0.0001 (41.4); −0.0057 (1.2) I-039 [00229] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5538 (4.2); 9.5422 (4.3); 9.3241 (9.6); 9.3217 (9.6); 8.7826 (5.1); 8.7801 (5.7); 8.7785 (7.4); 8.7760 (7.0); 8.7580 (11.4); 8.7539 (8.1); 8.6838 (6.8); 8.6830 (6.7); 8.6795 (7.1); 8.6787 (6.6); 8.2887 (5.6); 8.2861 (10.4); 8.2836 (5.9); 8.2743 (5.4); 8.2700 (5.2); 8.2598 (6.0); 8.2554 (6.0); 8.1854 (5.3); 8.1824 (8.3); 8.1796 (5.8); 8.1439 (6.0); 8.1411 (8.7); 8.1380 (4.8); 8.0340 (7.8); 8.0332 (7.5); 8.0196 (7.0); 8.0187 (6.6); 6.0803 (0.6); 6.0687 (3.1); 6.0571 (4.9); 6.0455 (3.1); 6.0339 (0.6); 5.7525 (0.5); 3.3135 (49.6); 3.3065 (301.9); 3.2833 (0.5); 2.6188 (0.8); 2.6158 (1.9); 2.6127 (2.7); 2.6097 (2.0); 2.6066 (0.9); 2.5368 (0.3); 2.5218 (6.1); 2.5187 (7.5); 2.5156 (7.3); 2.5068 (142.8); 2.5038 (303.6); 2.5007 (419.9); 2.4977 (305.6); 2.4947 (142.9); 2.3907 (0.8); 2.3877 (1.9); 2.3847 (2.6); 2.3817 (1.8); 2.3786 (0.8); 2.0724 (2.9); 518.0 [M + H].sup.+ 1.9069 (0.5); 1.7297 (15.9); 1.7180 (16.0); 0.0053 (0.7); −0.0001 (22.8); −0.0057 (0.7) I-040 [00230] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.4996 (3.9); 9.4881 (4.0); 9.3231 (9.2); 9.3207 (9.3); 8.7846 (4.8); 8.7820 (5.5); 8.7805 (7.1); 8.7780 (6.6); 8.7597 (11.0); 8.7556 (7.9); 8.6700 (6.6); 8.6692 (6.5); 8.6657 (6.9); 8.6650 (6.4); 8.2641 (5.1); 8.2598 (4.9); 8.2496 (5.7); 8.2453 (5.7); 8.1487 (6.6); 8.0893 (6.5); 8.0629 (5.9); 8.0255 (7.6); 8.0248 (7.3); 8.0110 (6.8); 8.0103 (6.5); 6.0673 (0.6); 6.0557 (2.9); 6.0441 (4.5); 6.0325 (2.9); 6.0209 (0.6); 4.0942 (1.0); 4.0854 (3.0); 4.0767 (3.1); 4.0679 (1.0); 3.3133 (44.2); 3.1785 (12.5); 3.1698 (12.3); 2.6174 (0.4); 2.5264 (0.8); 2.5234 (1.0); 2.5203 (1.0); 2.5115 (22.9); 2.5085 (49.5); 2.5054 (69.1); 2.5024 (50.6); 2.4993 (23.8); 2.3894 (0.4); 1.7313 (15.9); 1.7197 (16.0); −0.0001 (5.9). 508.0 [M + H].sup.+ I-041 [00231] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 10.8694 (1.2); 9.3294 (3.1); 9.3179 (3.2); 9.0421 (4.8); 9.0383 (4.8); 9.0232 (10.7); 9.0151 (10.7); 8.4415 (3.0); 8.4375 (2.9); 8.4276 (3.1); 8.4236 (3.0); 7.9216 (9.7); 7.9021 (3.6); 7.7922 (7.7); 7.7882 (16.0); 7.6897 (4.8); 7.6759 (7.6); 7.6678 (5.7); 7.6597 (2.9); 6.0483 (0.5); 6.0370 (2.1); 6.0254 (3.2); 6.0139 (2.1); 6.0022 (0.5); 3.3072 (209.0); 2.6129 (2.3); 2.5214 (8.2); 2.5185 (10.6); 2.5035 (296.2); 2.5008 (368.9); 2.4983 (283.9); 2.3849 (2.4); 1.7112 (11.3); 1.6996 (11.3); −0.0001 (19.7) 474.0 [M + H].sup.+ I-042 [00232] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.5688 (3.8); 9.5572 (3.9); 9.1772 (5.7); 9.1745 (5.7); 9.1204 (5.1); 9.1186 (5.0); 9.0615 (0.7); 9.0533 (1.0); 9.0492 (5.9); 9.0453 (6.0); 9.0335 (15.8); 9.0254 (16.0); 9.0145 (1.2); 9.0063 (0.4); 8.8889 (0.8); 8.8853 (0.7); 8.8632 (0.8); 8.5754 (1.1); 8.5674 (1.1); 8.5018 (5.6); 8.4485 (4.1); 8.4444 (4.0); 8.4346 (4.2); 8.4305 (4.2); 8.2872 (0.4); 8.2836 (0.4); 8.2733 (0.4); 8.2697 (0.4); 8.1318 (0.7); 7.7118 (0.4); 7.7040 (0.4); 7.6927 (6.5); 7.6790 (10.2); 7.6711 (8.4); 7.6631 (4.3); 7.6502 (0.4); 7.2432 (0.3); 6.1141 (0.6); 6.1026 (2.7); 6.0910 (4.2); 6.0793 (2.7); 6.0678 (0.6); 3.3190 (89.5); 3.1739 (0.3); 3.1652 (0.3); 2.6175 (1.0); 2.6146 (1.3); 2.6116 (1.0); 2.5235 (3.1); 2.5205 (3.9); 2.5173 (4.2); 2.5055 (151.3); 2.5025 (204.0); 2.4996 (151.3); 2.3893 (0.9); 2.3865 (1.3); 2.3836 (0.9); 1.8739 (0.9); 1.8623 (0.9); 1.7460 (14.7); 1.7344 (14.6); 1.7203 475.1 [M + H].sup.+ (0.5); 1.7088 (0.4); 1.6791 (0.6); 1.6675 (0.5); 1.2327 (0.4); 1.1043 (0.4); 1.0924 (0.8); 1.0806 (0.4); 0.0053 (0.5); −0.0001 (13.6); −0.0056 (0.5). I-043 [00233] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.4797 (3.2); 9.4681 (3.3); 9.0449 (4.9); 9.0440 (4.9); 9.0410 (5.1); 9.0400 (4.7); 9.0254 (15.7); 9.0173 (16.0); 8.4435 (4.0); 8.4395 (3.8); 8.4297 (4.2); 8.4256 (4.2); 8.1258 (5.2); 8.0636 (5.6); 8.0604 (5.1); 8.0568 (4.8); 7.9550 (1.3); 7.6896 (5.4); 7.6888 (5.2); 7.6756 (5.9); 7.6744 (7.4); 7.6658 (8.1); 7.6578 (4.1); 6.0832 (0.5); 6.0717 (2.4); 6.0600 (3.8); 6.0484 (2.4); 6.0368 (0.5); 3.3125 (70.5); 2.8926 (10.8); 2.7338 (8.8); 2.6915 (0.4); 2.6185 (0.4); 2.6156 (0.6); 2.6124 (0.4); 2.5246 (1.1); 2.5215 (1.3); 2.5184 (1.3); 2.5096 (30.6); 2.5066 (64.4); 2.5035 (88.2); 2.5004 (64.0); 2.4975 (29.9); 2.3905 (0.4); 2.3875 (0.5); 2.3844 (0.4); 1.7349 (12.6); 1.7233 (12.6); 1.2726 (0.5); 1.2591 (0.7); 1.2478 (0.6); −0.0001 (6.0). 508.1 [M + H].sup.+ I-044 [00234] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.7602 (2.7); 9.7485 (2.8); 9.3139 (6.7); 9.3115 (6.4); 9.0498 (15.8); 9.0417 (16.0); 8.7944 (3.9); 8.7919 (4.3); 8.7903 (5.2); 8.7878 (4.8); 8.7655 (7.8); 8.7614 (5.8); 8.2052 (6.7); 8.2034 (6.7); 8.1567 (6.4); 7.7012 (4.3); 7.6931 (8.1); 7.6851 (4.1); 6.1317 (0.5); 6.1201 (2.2); 6.1085 (3.5); 6.0969 (2.2); 6.0853 (0.5); 3.3071 (175.5); 3.2940 (0.6); 2.6193 (0.6); 2.6161 (1.2); 2.6131 (1.6); 2.6101 (1.1); 2.6070 (0.5); 2.5222 (4.4); 2.5191 (5.8); 2.5159 (6.8); 2.5072 (96.9); 2.5042 (195.0); 2.5011 (262.8); 2.4980 (189.0); 2.4950 (87.6); 2.3911 (0.6); 2.3881 (1.2); 2.3851 (1.6); 2.3820 (1.1); 2.3790 (0.5); 1.7520 (11.7); 1.7404 (11.7); 0.0053 (0.7); −0.0001 (19.6); −0.0057 (0.6) 476.2 [M + H].sup.+ I-045 [00235] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5659 (2.9); 9.5541 (3.0); 9.3095 (6.7); 9.3070 (6.6); 9.0468 (15.8); 9.0387 (16.0); 8.7894 (3.9); 8.7869 (4.4); 8.7853 (5.2); 8.7828 (4.8); 8.7597 (7.8); 8.7556 (5.9); 8.2604 (4.1); 8.2579 (7.4); 8.2553 (4.1); 8.1705 (3.9); 8.1675 (5.8); 8.1648 (4.1); 8.1355 (4.4); 8.1326 (6.1); 8.1295 (3.3); 7.6951 (4.2); 7.6870 (8.1); 7.6789 (4.1); 6.1142 (0.5); 6.1026 (2.2); 6.0910 (3.4); 6.0793 (2.2); 6.0676 (0.4); 3.3061 (207.5); 2.6188 (0.7); 2.6157 (1.4); 2.6126 (2.0); 2.6096 (1.4); 2.6065 (0.7); 2.5217 (5.4); 2.5186 (7.0); 2.5154 (8.1); 2.5068 (117.5); 2.5037 (235.4); 2.5006 (316.2); 2.4976 (226.8); 2.4946 (104.6); 2.3907 (0.7); 2.3876 (1.5); 2.3846 (2.0); 2.3816 (1.4); 2.3785 (0.6); 2.0853 (0.5); 2.0723 (0.6); 1.7481 (11.5); 1.7365 (11.5); 0.0053 485.1 [M + H].sup.+ (0.9): −0.0001 (23.0); −0.0057 (0.7) I-046 [00236] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.3708 (1.4); 9.3591 (1.5); 9.3048 (3.4); 9.3023 (3.3); 9.0413 (7.7); 9.0332 (7.8); 8.7901 (1.9); 8.7875 (2.2); 8.7860 (2.6); 8.7834 (2.4); 8.7599 (3.9); 8.7557 (3.0); 7.7997 (16.0); 7.6934 (2.1); 7.6853 (4.0); 7.6772 (2.0); 6.0565 (1.1); 6.0448 (1.8); 6.0332 (1.1); 3.3067 (94.6); 2.6190 (0.3); 2.6159 (0.7); 2.6129 (0.9); 2.6098 (0.6); 2.5219 (2.6); 2.5188 (3.3); 2.5157 (3.8); 2.5069 (57.1); 2.5039 (114.4); 2.5009 (153.9); 2.4978 (110.8); 2.4948 (51.6); 2.3910 (0.4); 2.3879 (0.7); 2.3848 (1.0); 2.3817 (0.7); 1.7225 (6.0); 1.7109 (6.0); 0.0053 (0.4); −0.0001 (9.3) 441.1 [M + H].sup.+ I-047 [00237] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.5221 (3.0); 9.5104 (3.1); 9.3068 (6.8); 9.3044 (6.9); 9.0429 (15.7); 9.0348 (16.0); 8.7893 (3.7); 8.7867 (4.3); 8.7852 (5.3); 8.7826 (4.9); 8.7598 (8.1); 8.7557 (6.1); 8.1378 (5.1); 8.0811 (5.1); 8.0592 (4.5); 7.6911 (4.2); 7.6831 (8.1); 7.6750 (4.1); 6.1025 (0.5); 6.0909 (2.3); 6.0793 (3.7); 6.0676 (2.4); 6.0560 (0.5); 3.3078 (107.1); 2.6168 (0.6); 2.6138 (0.9); 2.6108 (0.6); 2.5229 (1.8); 2.5198 (2.2); 2.5167 (2.0); 2.5079 (49.1); 2.5049 (106.0); 2.5018 (148.2); 2.4987 (108.5); 2.4957 (51.0); 2.3888 (0.6); 2.3858 (0.9); 2.3827 (0.6); 1.7449 (12.5); 1.7333 (12.6); 0.0053 (0.4); −0.0001 (14.2); −0.0057 (0.4). 475.1 [M + H].sup.+ I-048 [00238] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5179 (2.7); 9.5062 (2.7); 9.3057 (6.4); 9.3032 (6.3); 9.0415 (15.8); 9.0334 (16.0); 8.7887 (3.8); 8.7861 (4.2); 8.7846 (5.1); 8.7820 (4.8); 8.7592 (7.5); 8.7551 (5.7); 8.2704 (4.6); 8.1623 (4.1); 8.1093 (4.4); 7.6903 (4.2); 7.6822 (8.0); 7.6741 (4.1); 6.0979 (0.4); 6.0864 (2.1); 6.0748 (3.3); 6.0631 (2.1); 6.0515 (0.4); 5.7524 (0.6); 3.3061 (350.3); 3.2827 (0.5); 2.6186 (1.0); 2.6156 (2.2); 2.6126 (2.9); 2.6095 (2.0); 2.6064 (0.9); 2.5369 (0.5); 2.5216 (8.1); 2.5185 (10.6); 2.5154 (12.4); 2.5067 (174.2); 2.5037 (352.2); 2.5006 (476.3); 2.4975 (341.8); 2.4945 (156.8); 2.3907 (1.1); 2.3876 (2.2); 2.3845 (3.0); 2.3815 (2.0); 2.3784 (0.9); 1.7416 (11.1); 1.7300 (11.1); 0.0053 (1.0); −0.0001 (27.0); −0.0057 (0.8) 521.1 [M + H].sup.+ I-049 [00239] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.6129 (1.3); 9.6013 (1.3); 9.3124 (3.3); 9.3099 (3.2); 9.0461 (7.9); 9.0380 (8.0); 8.7959 (2.0); 8.7933 (2.1); 8.7918 (2.6); 8.7892 (2.4); 8.7658 (3.8); 8.7617 (2.9); 7.8404 (16.0); 7.7009 (2.2); 7.6928 (4.1); 7.6847 (2.1); 6.0789 (1.0); 6.0673 (1.6); 6.0557 (1.0); 3.3066 (89.0); 2.6159 (0.6); 2.6128 (0.8); 2.6098 (0.6); 2.5219 (2.4); 2.5188 (3.1); 2.5156 (3.6); 2.5070 (50.8); 2.5039 (102.6); 2.5008 (138.9); 2.4978 (99.9); 2.4947 (46.2); 2.3910 (0.3); 2.3879 (0.6); 2.3848 (0.9); 2.3818 (0.6); 1.7286 (5.9); 1.7170 (5.9); 0.0053 (0.4); −0.0001 (10.1) 442.1 [M].sup.+ I-050 [00240] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.6025 (2.8); 9.5908 (2.8); 9.3115 (6.7); 9.3091 (6.5); 9.1850 (4.4); 9.1819 (4.3); 9.1185 (3.8); 9.1164 (3.7); 9.0492 (15.8); 9.0411 (16.0); 8.7899 (3.9); 8.7873 (4.3); 8.7857 (5.2); 8.7832 (4.8); 8.7606 (7.8); 8.7565 (5.8); 8.5188 (4.2); 8.5155 (2.4); 7.6945 (4.3); 7.6864 (8.2); 7.6783 (4.2); 6.1340 (0.5); 6.1225 (2.3); 6.1109 (3.6); 6.0992 (2.3); 6.0876 (0.5); 3.3071 (172.8); 2.6192 (0.6); 2.6162 (1.2); 2.6131 (1.6); 2.6101 (1.1); 2.6071 (0.5); 2.5222 (4.3); 2.5191 (5.7); 2.5159 (6.7); 2.5072 (91.7); 2.5042 (184.2); 2.5011 (248.2); 2.4981 (178.7); 2.4950 (83.2); 2.3912 (0.5); 2.3881 (1.1); 2.3851 (1.5); 2.3820 (1.0); 2.3790 (0.5); 1.7576 (12.1); 1.7460 (12.1); 0.0053 (0.8); −0.0001 (21.7); −0.0056 (0.7) 442.2 [M + H].sup.+ I-051 [00241] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4763 (2.2); 9.4586 (2.3); 9.0391 (11.0); 9.0270 (11.3); 8.9675 (10.3); 8.9553 (10.6); 7.9485 (3.1); 7.9448 (4.9); 7.9410 (3.2); 7.7752 (3.5); 7.7243 (3.5); 7.6900 (2.9); 7.6778 (5.5); 7.6657 (2.8); 7.6177 (2.8); 7.6056 (5.4); 7.5934 (2.7); 6.0943 (0.4); 6.0771 (1.6); 6.0596 (2.6); 6.0422 (1.7); 6.0246 (0.4); 5.7581 (16.0); 3.3321 (117.6); 3.1764 (0.9); 3.1633 (0.8); 2.6773 (0.7); 2.6728 (0.9); 2.6684 (0.7); 2.5262 (3.2); 2.5125 (62.4); 2.5084 (122.0); 2.5039 (156.2); 2.4994 (112.7); 2.4951 (55.3); 2.3353 (0.6); 2.3307 (0.9); 2.3262 (0.6); 1.7285 (9.0); 1.7111 (9.0); −0.0002 (2.1) 491.1 [M + H].sup.+ I-052 [00242] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5846 (3.0); 9.5727 (3.1); 9.0412 (15.6); 9.0331 (15.9); 8.9624 (15.7); 8.9543 (16.0); 8.2773 (3.9); 8.2748 (7.3); 8.2722 (4.2); 8.1829 (3.8); 8.1800 (5.9); 8.1772 (4.0); 8.1339 (4.2); 8.1310 (6.2); 8.1280 (3.5); 7.6885 (4.2); 7.6804 (8.0); 7.6723 (4.1); 7.6091 (4.2); 7.6010 (8.1); 7.5929 (4.1); 6.1167 (0.5); 6.1052 (2.2); 6.0934 (3.4); 6.0817 (2.2); 6.0701 (0.5); 3.3076 (274.6); 3.2841 (0.5); 2.6188 (0.6); 2.6158 (1.3); 2.6128 (1.8); 2.6097 (1.3); 2.6067 (0.6); 2.5218 (4.2); 2.5187 (5.1); 2.5156 (5.0); 2.5068 (99.5); 2.5038 (210.4); 2.5007 (290.4); 2.4977 (211.8); 2.4947 (99.9); 2.3908 (0.6); 2.3878 (1.3); 2.3847 (1.8); 2.3817 (1.3); 2.3786 (0.6); 1.7378 (11.5); 1.7262 (11.6); 0.0053 (0.9); −0.0001 (29.6); −0.0057 (0.9) 485.1 [M + H].sup.+ I-053 [00243] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 14.7997 (0.5); 9.6442 (1.8); 9.6263 (1.9); 9.1939 (3.0); 9.1895 (3.1); 9.1230 (2.8); 9.1200 (2.8); 9.0487 (10.9); 9.0365 (11.2); 8.9987 (0.8); 8.9674 (11.0); 8.9552 (11.7); 8.9392 (1.2); 8.8744 (0.4); 8.8300 (0.6); 8.5421 (3.4); 8.5270 (1.1); 8.1565 (0.6); 7.6954 (2.8); 7.6833 (5.4); 7.6711 (2.8); 7.6179 (2.9); 7.6057 (5.6); 7.5935 (3.1); 7.1857 (0.5); 6.2713 (0.4); 6.2532 (0.4); 6.1328 (1.4); 6.1153 (2.2); 6.0977 (1.4); 5.7577 (16.0); 3.3342 (177.3); 2.8921 (0.6); 2.7332 (0.6); 2.7319 (0.6); 2.6904 (0.5); 2.6816 (0.4); 2.6775 (0.7); 2.6729 (1.0); 2.6684 (0.7); 2.5264 (3.3); 2.5216 (5.3); 2.5129 (63.3); 2.5085 (126.5); 2.5040 (163.0); 2.4994 (116.1); 2.4949 (55.2); 2.3398 (0.3); 2.3353 (0.7); 2.3307 (1.0); 2.3262 (0.7); 2.3217 (0.3); 1.9270 (1.2); 442.2 [M + H].sup.+ 1.9096 (1.3); 1.7525 (7.6); 1.7351 (7.5); 1.2750 (0.6); 1.2593 (1.3); 1.2440 (0.9); −0.0002 (2.7) I-054 [00244] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4076 (2.2); 9.3898 (2.3); 9.0412 (12.4); 9.0290 (12.8); 8.9680 (11.9); 8.9558 (12.2); 7.8195 (7.6); 7.8152 (16.0); 7.8075 (6.0); 7.8035 (4.2); 7.7983 (1.8); 7.6940 (3.3); 7.6819 (6.2); 7.6697 (3.2); 7.6177 (3.2); 7.6055 (6.2); 7.5934 (3.2); 6.0832 (0.3); 6.0656 (1.6); 6.0481 (2.6); 6.0306 (1.7); 6.0132 (0.4); 5.7579 (8.0); 3.3339 (164.0); 2.6773 (0.6); 2.6728 (0.8); 2.6684 (0.6); 2.5263 (2.8); 2.5127 (54.9); 2.5084 (108.5); 2.5039 (139.6); 2.4993 (99.8); 2.4948 (47.9); 2.3352 (0.6); 2.3307 (0.8); 2.3261 (0.6); 1.7162 (9.0); 1.6988 (8.9); −0.0002 (1.9) 441.1 [M + H].sup.+ I-055 [00245] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5624 (2.3); 9.5446 (2.4); 9.0427 (13.4); 9.0305 (13.7); 8.9665 (13.1); 8.9543 (13.5); 8.1522 (4.3); 8.1032 (4.2); 8.0661 (3.9); 7.6921 (3.5); 7.6800 (6.6); 7.6678 (3.4); 7.6169 (3.5); 7.6047 (6.6); 7.5926 (3.4); 7.2842 (0.7); 7.2616 (0.7); 6.1178 (0.4); 6.1006 (1.7); 6.0830 (2.8); 6.0655 (1.8); 6.0485 (0.4); 5.7581 (16.0); 3.3330 (154.7); 3.1765 (0.6); 3.1634 (0.6); 2.6819 (0.3); 2.6775 (0.7); 2.6730 (0.9); 2.6684 (0.7); 2.6639 (0.3); 2.5265 (3.2); 2.5216 (5.2); 2.5130 (61.2); 2.5086 (122.8); 2.5040 (158.8); 2.4994 (113.4); 2.4950 (54.3); 2.3353 (0.6); 2.3308 (0.9); 2.3264 (0.7); 1.7382 (9.4); 1.7208 (9.4); 1.6497 (0.9); −0.0002 (2.0) 475.3 [M + H].sup.+ I-056 [00246] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.8013 (2.4); 9.7837 (2.4); 9.0483 (11.7); 9.0362 (12.0); 8.9721 (10.0); 8.9599 (10.3); 8.2264 (6.0); 8.2243 (6.1); 8.1688 (6.1); 8.1406 (0.4); 7.7013 (3.1); 7.6891 (5.9); 7.6770 (3.0); 7.6231 (2.8); 7.6109 (5.3); 7.5987 (2.7); 6.1491 (0.4); 6.1320 (1.7); 6.1146 (2.7); 6.0970 (1.7); 6.0800 (0.4); 5.7573 (16.0); 3.3330 (120.1); 3.1760 (0.6); 3.1636 (0.5); 2.6774 (0.8); 2.6728 (1.1); 2.6684 (0.8); 2.5260 (3.8); 2.5124 (74.1); 2.5084 (141.2); 2.5039 (178.0); 2.4994 (129.6); 2.4954 (64.5); 2.3351 (0.8); 2.3307 (1.0); 2.3262 (0.8): 1.7472 (9.4); 1.7298 (9.4); −0.0002 (2.3) 476.3 [M + H].sup.+ I-057 [00247] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5528 (2.2); 9.5353 (2.2); 9.0122 (10.2); 9.0001 (10.5); 8.2737 (3.0); 8.2701 (5.4); 8.2665 (3.3); 8.1781 (2.8); 8.1737 (4.8); 8.1698 (3.2); 8.1416 (3.4); 8.1374 (4.8); 8.1331 (2.5); 7.8677 (4.4); 7.8652 (4.3); 7.6563 (2.7); 7.6442 (5.1); 7.6320 (2.6); 7.0594 (3.8); 7.0522 (3.8); 7.0509 (3.8); 6.6757 (3.1); 6.6713 (3.2); 6.6673 (3.1); 6.6628 (2.9); 6.0904 (1.5); 6.0730 (2.4); 6.0555 (1.6); 6.0379 (0.3); 5.7570 (16.0); 4.1054 (0.4); 4.0922 (0.4); 3.3958 (1.0); 3.3308 (107.7); 3.3144 (23.8); 3.1760 (2.1); 3.1629 (2.1); 2.6767 (0.6); 2.6723 (0.8); 2.6676 (0.6); 2.5253 (2.9); 2.5116 (57.9); 2.5077 (110.0); 2.5032 (138.7); 2.4987 (99.9); 2.4946 (49.0); 2.3345 (0.6); 2.3301 (0.8); 2.3255 (0.6); 1.7087 (8.4); 1.6913 (8.4); 1.2591 (0.5); 1.2504 473.3 [M + H].sup.+ (0.5); 1.2427 (0.4); 1.2340 (0.5); −0.0002 (1.5) I-058 [00248] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5082 (2.2); 9.4905 (2.3); 9.0074 (11.5); 8.9953 (11.9); 8.1440 (4.2); 8.0926 (4.2); 8.0660 (3.8); 7.8667 (4.6); 7.8642 (4.6); 7.8626 (4.2); 7.6516 (3.0); 7.6394 (5.8); 7.6273 (3.0); 7.0558 (3.8); 7.0543 (4.1); 7.0474 (4.0); 7.0459 (4.1); 6.6753 (3.4); 6.6708 (3.5); 6.6668 (3.4); 6.6624 (3.4); 6.0945 (0.3); 6.0773 (1.7); 6.0599 (2.7); 6.0424 (1.7); 6.0251 (0.4); 5.7576 (16.0); 3.3312 (113.7); 3.1764 (0.6); 3.1633 (0.6); 2.6772 (0.7); 2.6727 (0.9); 2.6682 (0.7); 2.5260 (3.0); 2.5125 (58.3); 2.5082 (116.2); 2.5037 (150.5); 2.4992 (109.0); 2.4948 (53.4); 2.3350 (0.6); 2.3306 (0.9); 2.3260 (0.6); 1.7050 (9.3); 1.6876 (9.2); −0.0002 (1.9) 463.3 [M + H].sup.+ I-059 [00249] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.4380 (1.2); 9.4263 (1.2); 8.6161 (2.0); 8.6154 (2.1); 8.6119 (2.0); 8.6110 (2.0); 8.2799 (1.7); 8.2773 (3.1); 8.2748 (1.8); 8.1961 (1.6); 8.1917 (1.6); 8.1815 (1.8); 8.1772 (1.9); 8.1744 (1.6); 8.1713 (2.6); 8.1686 (1.8); 8.1438 (1.8); 8.1409 (2.6); 8.1378 (1.4); 7.8733 (2.2); 7.8725 (2.3); 7.8588 (2.1); 7.8579 (2.1); 5.9879 (0.9); 5.9762 (1.5); 5.9646 (1.0); 3.3190 (13.8); 3.3097 (12.0); 2.5930 (16.0); 2.5176 (0.4); 2.5089 (6.0); 2.5059 (12.3); 2.5029 (16.8); 2.4998 (12.1); 2.4968 (5.6); 1.6275 (4.9); 1.6159 (4.9). 486.1 [M + H].sup.+ I-060 [00250] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.5344 (4.3); 9.5228 (4.5); 8.6914 (7.0); 8.6872 (7.1); 8.2840 (4.8); 8.2798 (4.6); 8.2696 (5.2); 8.2653 (5.2); 8.2415 (5.1); 8.2390 (9.7); 8.2365 (5.7); 8.1543 (4.5); 8.1514 (8.5); 8.1485 (5.3); 8.1282 (5.9); 8.1254 (8.4); 8.1225 (4.6); 7.9406 (7.8); 7.9261 (7.2); 5.9662 (0.6); 5.9546 (3.0); 5.9431 (4.8); 5.9315 (3.1); 5.9198 (0.6); 3.4531 (53.6); 3.3350 (0.4); 3.3177 (56.9); 2.6173 (0.4); 2.6143 (0.6); 2.6113 (0.4); 2.5233 (1.4); 2.5202 (1.7); 2.5171 (1.7); 2.5082 (30.5); 2.5053 (64.3); 2.5022 (89.9); 2.4992 (67.4); 2.4963 (32.2); 2.3892 (0.4); 2.3862 (0.6); 2.3831 (0.4); 2.0752 (0.4); 1.6834 (15.9); 1.6718 (16.0); 0.0053 (0.4); −0.0001 (12.6); −0.0056 (0.4). 518.1 [M + H].sup.+ I-061 [00251] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5539 (2.0); 9.5367 (2.0); 8.6869 (2.5); 8.6816 (4.3); 8.6763 (2.5); 8.2731 (2.1); 8.2669 (2.1); 8.2515 (7.3); 8.1518 (5.6); 8.1470 (6.8); 8.1425 (5.1); 7.9423 (4.6); 7.9205 (4.2); 7.8722 (0.8); 7.6144 (0.4); 7.5968 (0.6); 7.4913 (0.5); 5.9862 (1.0); 5.9812 (1.1); 5.9688 (1.6); 5.9639 (1.6); 5.9513 (1.1); 5.9465 (1.0); 3.3639 (44.1); 3.3205 (32.7); 3.1450 (0.6); 3.0496 (16.0); 3.0402 (15.3); 2.9984 (1.5); 2.7152 (0.3); 2.6791 (0.7); 2.6749 (0.9); 2.6706 (0.6); 2.5452 (67.8); 2.5280 (2.9); 2.5103 (112.0); 2.5059 (141.5); 2.5015 (102.5); 2.3370 (0.6); 2.3327 (0.8); 2.3284 (0.6); 1.6903 (5.7); 1.6853 (5.7); 1.6729 (5.9); 1.6680 (5.4); 1.2364 (0.5) 502.0 [M + H].sup.+ I-062 [00252] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4043 (1.2); 9.3869 (1.2); 8.6063 (2.3); 8.6010 (2.3); 8.5998 (2.2); 8.1961 (1.6); 8.1896 (1.5); 8.1742 (1.8); 8.1677 (1.8); 8.1387 (2.2); 8.0803 (2.4); 8.0746 (2.0); 8.0729 (2.0); 8.0696 (2.1); 7.8703 (2.4); 7.8693 (2.4); 7.8485 (2.1); 7.8474 (2.1); 5.9740 (0.9); 5.9565 (1.4); 5.9391 (0.9); 5.7574 (6.6); 3.3308 (63.4); 2.6770 (0.3); 2.6724 (0.4); 2.6680 (0.3); 2.5890 (16.0); 2.5259 (1.5); 2.5211 (2.4); 2.5124 (28.5); 2.5080 (57.0); 2.5035 (73.9); 2.4990 (53.2); 2.4945 (25.8); 2.3304 (0.4); 1.6256 (4.9); 1.6082 (4.9); −0.0002 (0.9) 476.0 [M + H].sup.+ I-063 [00253] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4770 (3.0); 9.4598 (3.0); 8.6751 (5.7); 8.6698 (5.7); 8.2760 (4.0); 8.2696 (3.8); 8.2543 (4.5); 8.2479 (4.4); 8.0880 (5.5); 8.0844 (5.2); 8.0760 (5.2); 8.0242 (5.2); 7.9330 (5.9); 7.9123 (5.2); 7.9111 (5.3); 5.9608 (0.5); 5.9436 (2.2); 5.9263 (3.5); 5.9089 (2.2); 5.8912 (0.4); 5.7568 (16.0); 3.4507 (43.6); 3.3311 (186.8); 3.1758 (0.9); 3.1626 (0.9); 2.6769 (0.8); 2.6722 (1.2); 2.6676 (0.8); 2.5257 (4.2); 2.5122 (76.0); 2.5078 (149.6); 2.5032 (191.3); 2.4986 (135.1); 2.4941 (63.9); 2.3346 (0.8); 2.3300 (1.1); 2.3253 (0.8); 1.6830 (11.8); 1.6655 (11.8); −0.0002 (2.2) 508.1 [M + H].sup.+ I-064 [00254] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4823 (2.2); 9.4652 (2.2); 8.6709 (2.5); 8.6644 (4.1); 8.6588 (2.2); 8.2610 (1.6); 8.2581 (1.8); 8.2548 (1.9); 8.2517 (1.6); 8.2393 (1.9); 8.2363 (2.0); 8.2329 (2.0); 8.2300 (1.8); 8.1018 (3.9); 8.0781 (4.0); 8.0396 (3.9); 8.0241 (0.4); 7.9294 (4.3); 7.9077 (3.9); 5.9684 (0.9); 5.9623 (1.0); 5.9510 (1.5); 5.9449 (1.6); 5.9337 (1.0); 5.9275 (1.0); 3.4522 (3.0); 3.3348 (156.4); 3.0464 (15.6); 3.0353 (16.0); 2.9971 (1.1); 2.6769 (0.6); 2.6724 (0.8); 2.6679 (0.6); 2.5429 (69.5); 2.5259 (2.5); 2.5212 (3.7); 2.5124 (48.4); 2.5080 (97.3); 2.5035 (125.8); 2.4990 (91.4); 2.4946 (45.1); 2.3349 (0.5); 2.3303 (0.7); 2.3259 (0.5); 1.6857 (5.6); 1.6809 (6.0); 1.6683 (5.8); 1.6635 (5.8); 1.2379 (0.4); −0.0002 (0.6) 492.0 [M + H].sup.+ I-065 [00255] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4734 (2.4); 9.4563 (2.5); 8.6378 (4.4); 8.6367 (4.6); 8.6315 (4.7); 8.6302 (4.5); 8.3162 (0.4); 8.2623 (3.5); 8.2585 (6.4); 8.2547 (3.8); 8.2302 (3.3); 8.2238 (3.1); 8.2084 (3.7); 8.2019 (3.6); 8.1506 (13.0); 8.1468 (11.9); 7.8961 (4.7); 7.8950 (4.7); 7.8744 (4.2); 7.8731 (4.3); 5.9911 (0.4); 5.9735 (1.7); 5.9562 (2.7); 5.9388 (1.8); 5.9212 (0.4); 5.7566 (16.0); 4.2483 (1.2); 4.2228 (4.0); 4.1972 (4.2); 4.1716 (1.4); 3.3301 (177.2); 3.3176 (29.2); 3.1756 (0.8); 3.1625 (0.7); 2.6764 (0.9); 2.6719 (1.2); 2.6673 (0.9); 2.5253 (4.0); 2.5205 (6.4); 2.5119 (77.9); 2.5075 (154.8); 2.5029 (199.2); 2.4983 (141.9); 2.4939 (68.2); 2.3387 (0.4); 2.3342 (0.8); 2.3297 (1.2); 2.3252 (0.8); 1.6378 554.0 [M + H].sup.+ (9.2); 1.6204 (9.2); −0.0002 (2.5) I-066 [00256] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5604 (2.8); 9.5434 (2.8); 8.7135 (3.0); 8.7071 (3.4); 8.6975 (2.5); 8.3156 (0.5); 8.3032 (1.8); 8.2980 (2.5); 8.2921 (2.0); 8.2815 (2.1); 8.2761 (2.8); 8.2704 (1.9); 8.2491 (6.0); 8.2459 (3.8); 8.2263 (0.6); 8.2227 (0.4); 8.1594 (3.1); 8.1550 (6.4); 8.1510 (4.6); 8.1426 (4.5); 8.1390 (5.3); 8.1118 (0.4); 8.1077 (0.5); 7.9809 (3.0); 7.9774 (3.0); 7.9591 (3.1); 7.9557 (2.8); 7.9373 (0.5); 5.9947 (1.1); 5.9872 (1.1); 5.9775 (1.7); 5.9700 (1.6); 5.9602 (1.2); 5.9529 (1.0); 5.9417 (0.4); 5.7563 (16.0); 5.2115 (0.5); 5.1875 (0.5); 4.6095 (0.6); 4.5932 (0.9); 4.5836 (2.0); 4.5808 (1.9); 4.5669 (2.1); 4.5625 (2.1); 4.5572 (2.2); 4.5537 (2.1); 4.5404 (1.9); 4.5357 (2.0); 4.5266 (0.9); 4.5138 (0.6); 4.5087 (0.6); 3.3299 (193.6); 3.3168 (31.2); 3.1752 (0.8); 3.1621 (0.8); 2.6759 (1.0); 2.6715 (1.3); 2.6670 (1.0); 2.5248 570.0 [M + H].sup.+ (4.5); 2.5112 (88.4); 2.5070 (171.1); 2.5026 (217.8); 2.4981 (157.4); 2.4937 (77.3); 2.3338 (0.9); 2.3294 (1.2); 2.3250 (0.9); 1.7035 (5.6); 1.6959 (6.6); 1.6861 (6.1); 1.6785 (6.3); −0.0002 (2.4) I-067 [00257] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4210 (3.0); 9.4038 (3.0); 8.6270 (5.7); 8.6208 (5.7); 8.2217 (3.4); 8.2153 (3.2); 8.1998 (3.8); 8.1934 (3.8); 8.1130 (5.6); 8.0716 (5.4); 8.0518 (5.6); 7.8875 (5.9); 7.8656 (5.2); 5.9721 (0.5); 5.9547 (2.2); 5.9374 (3.4); 5.9201 (2.2); 5.9032 (0.4); 5.7574 (16.0); 4.2420 (1.6); 4.2166 (5.0); 4.1910 (5.2); 4.1654 (1.8); 3.3302 (120.4); 3.1762 (0.8); 3.1631 (0.8); 2.6769 (0.9); 2.6725 (1.2); 2.6680 (0.9); 2.5256 (4.4); 2.5120 (81.7); 2.5080 (156.1); 2.5035 (197.8); 2.4990 (143.2); 2.4950 (71.0); 2.3347 (0.8); 2.3303 (1.2); 2.3259 (0.8); 1.6354 (12.1); 1.6179 (12.0); −0.0002 (2.1) 544.1 [M + H].sup.+ I-068 [00258] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5030 (1.4); 9.4973 (1.7); 9.4862 (1.6); 9.4803 (1.6); 8.7021 (2.6); 8.6957 (2.8); 8.6881 (2.1); 8.6829 (2.0); 8.6817 (2.0); 8.3024 (0.5); 8.2957 (0.7); 8.2925 (1.5); 8.2859 (2.7); 8.2795 (1.6); 8.2742 (0.9); 8.2707 (1.7); 8.2641 (3.0); 8.2576 (1.5); 8.1020 (3.8); 8.0783 (4.4); 8.0377 (3.8); 8.0044 (0.6); 7.9692 (2.7); 7.9676 (2.8); 7.9489 (2.8); 7.9477 (2.7); 7.9459 (2.5); 7.9284 (0.6); 5.9770 (0.9); 5.9707 (0.9); 5.9597 (1.4); 5.9534 (1.4); 5.9423 (1.0); 5.9361 (0.9); 5.9245 (0.5); 5.9074 (0.4); 5.7567 (16.0); 5.2062 (0.7); 5.1820 (0.7); 4.6081 (0.4); 4.6039 (0.4); 4.5820 (1.7); 4.5768 (1.4); 4.5568 (2.6); 4.5498 (1.6); 4.5305 (2.1); 4.5229 (0.6); 4.5036 (0.6); 3.3323 (207.2); 3.1758 (1.0); 3.1626 (1.0); 2.6767 (0.8); 2.6721 (1.0); 2.6676 (0.8); 2.5256 (3.6); 2.5120 (69.3); 2.5077 (136.2); 2.5032 (174.4); 560.0 [M + H].sup.+ 2.4986 (125.8); 2.4942 (61.2); 2.3387 (0.4); 2.3345 (0.7); 2.3300 (1.0); 2.3255 (0.8); 1.7006 (4.8); 1.6941 (5.6); 1.6832(5.1); 1.6766 (5.4); −0.0002 (1.9) I-069 [00259] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.5471 (3.9); 9.5360 (4.0); 8.7137 (6.9); 8.7128 (6.7); 8.7094 (7.1); 8.7085 (6.4); 8.2702 (5.5); 8.2659 (5.2); 8.2557 (5.9); 8.2514 (5.8); 8.2330 (5.6); 8.2305 (10.4); 8.2279 (5.9); 8.1553 (5.2); 8.1522 (8.5); 8.1493 (5.4); 8.1134 (6.2); 8.1107 (8.2); 8.1076 (5.0); 7.9013 (7.6); 7.9005 (7.1); 7.8868 (7.1); 7.8859 (6.7); 5.9141 (0.6); 5.9025 (2.8); 5.8911 (4.3); 5.8796 (2.8); 5.8680 (0.6); 3.3129 (51.5); 3.3063 (260.2); 3.2827 (0.5); 2.6187 (0.9); 2.6157 (1.8); 2.6126 (2.4); 2.6096 (1.7); 2.6066 (0.8); 2.5217 (6.6); 2.5186 (8.6); 2.5155 (10.2); 2.5068 (142.8); 2.5037 (289.0); 2.5007 (391.2); 2.4976 (281.8); 2.4946 (130.8); 2.3907 (0.9); 2.3877 (1.8); 2.3846 (2.4); 2.3815 (1.7); 2.3785 (0.8); 1.6686 (16.0); 1.6569 (15.9); 0.0053 (1.0); −0.0001 (25.8); −0.0057 (0.8) 640.0 [M + H].sup.+ I-070 [00260] .sup.1H-NMR (600.4 MHz, d.sub.6-DMSO): δ = 9.4959 (3.8); 9.4848 (3.9); 8.7064 (6.6); 8.7056 (6.5); 8.7021 (6.8); 8.7013 (6.2); 8.2626 (5.1); 8.2583 (4.9); 8.2481 (5.5); 8.2438 (5.4); 8.0756 (11.5); 8.0107 (6.5); 7.8955 (7.3); 7.8810 (6.8); 7.8802 (6.5); 5.8963 (0.6); 5.8847 (2.8); 5.8733 (4.3); 5.8618 (2.8); 5.8502 (0.6); 3.3067 (340.4); 3.2825 (0.6); 2.6188 (1.0); 2.6158 (2.1); 2.6128 (2.9); 2.6097 (2.0); 2.6066 (0.9); 2.5218 (7.6); 2.5187 (9.8); 2.5156 (11.3); 2.5069 (171.1); 2.5038 (344.2); 2.5008 (463.6); 2.4977 (335.2); 2.4947 (156.6); 2.3908 (1.0); 2.3878 (2.1); 2.3847 (2.8); 2.3817 (2.0); 2.3787 (0.9); 1.6658 (16.0); 1.6541 (16.0); 0.0053 (1.2); −0.0001 (29.9); −0.0057 (0.9) 630.0 [M + H].sup.+ I-071 [00261] .sup.1H-NMR (600 MHz, d.sub.6-DMSO, ppm): δ = 9.4261 (3.4); 9.4150 (3.5); 8.6835 (6.2); 8.6827 (6.2); 8.6793 (6.6); 8.6784 (6.2); 8.2770 (5.2); 8.2727 (5.0); 8.2626 (5.6); 8.2583 (5.6); 8.0896 (6.2); 8.0872 (4.6); 8.0702 (5.6); 8.0248 (6.1); 7.9436 (7.3); 7.9427 (7.0); 7.9291 (6.7); 7.9282 (6.5); 5.9349 (0.6); 5.9234 (2.7); 5.9120 (4.2); 5.9005 (2.8); 5.8890 (0.6); 3.3106 (34.6); 2.6166 (0.3); 2.5256 (0.7); 2.5226 (0.8); 2.5195 (0.8); 2.5107 (18.0); 2.5077 (38.6); 2.5046 (53.6); 2.5016 (39.0); 2.4985 (18.3); 2.3886 (0.3); 2.0760 (0.6); 1.6647 (15.9); 1.6531 (16.0); −0.0001 (1.9). 455.1 [M + H].sup.+ I-072 [00262] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4845 (2.0); 9.4608 (2.0); 9.0248 (15.6); 9.0085 (16.0); 8.1180 (5.2); 8.0638 (11.0); 7.6967 (3.8); 7.6804 (7.1); 7.6642 (3.6); 6.0407 (0.4); 6.0177 (1.7); 5.9942 (2.8); 5.9807 (1.0); 5.9707 (1.8); 5.9483 (0.3); 3.3143 (95.7); 2.7332 (1.0); 2.7270 (1.3); 2.7206 (0.8); 2.5130 (83.9); 2.5070 (162.9); 2.5009 (215.8); 2.4949 (146.0); 2.4890 (66.0); 2.2770 (0.9); 2.2708 (1.2); 2.2646 (0.9); 1.9088 (0.4); 1.6790 (10.6); 1.6558 (10.4); 1.2349 (1.9); 1.1662 (0.4); 1.1466 (0.4); 0.4842 (0.7); 0.0106 (1.0); −0.0003 (28.4); −0.0114 (0.9). I-073 [00263] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.5082 (4.2); 9.4854 (4.2); 9.0893 (8.4); 9.0842 (8.6); 8.6227 (6.5); 8.6154 (6.1); 8.5942 (7.1); 8.5868 (7.0); 8.1587 (7.8); 8.1021 (15.7); 8.0737 (15.5); 6.1150 (0.7); 6.0911 (2.6); 6.0681 (4.0); 6.0452 (2.6); 6.0221 (0.7); 3.8979 (0.4); 3.3145 (128.3); 2.7330 (1.4); 2.7272 (1.9); 2.7208 (1.4); 2.6550 (0.4); 2.5131 (120.7); 2.5071 (236.4); 2.5011 (314.8); 2.4951 (213.4); 2.4891 (96.6); 2.2770 (1.3); 2.2711 (1.9); 2.2648 (1.3); 1.9091 (0.5); 1.6742 (16.0); 1.6512 (15.8); 1.2348 (1.4); 1.1578 (0.6); 1.1471 (0.5); 1.1334 (0.4); 0.8550 (0.3); 0.8300 (0.4); 0.0107 (1.6); −0.0003 (43.6); −0.0113 (1.2). I-074 [00264] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4411 (2.7); 9.4181 (2.8); 9.0179 (15.5); 9.0016 (16.0); 8.9422 (0.7); 8.9259 (0.7); 8.1082 (4.8); 8.0622 (5.1); 8.0481 (5.2): 8.0221 (0.3); 7.9255 (2.6); 7.7229 (2.6); 7.6889 (4.3); 7.6726 (7.8); 7.6564 (4.0); 6.0202 (0.4); 5.9970 (1.9); 5.9737 (3.0); 5.9507 (1.9); 5.9277 (0.4); 3.3209 (56.9); 3.2989 (25.6); 3.0842 (0.7); 3.0108 (0.5); 2.7332 (1.0); 2.7272 (1.4); 2.7210 (1.0); 2.5132 (87.2); 2.5072 (171.7); 2.5012 (228.9); 2.4952 (157.3); 2.4894 (72.3); 2.2771 (1.0); 2.2711 (1.4); 2.2650 (1.0); 2.0744 (2.7); 1.9097 (0.7); 1.6856 (10.2); 1.6625 (10.1); 1.2357 (0.4); 1.1493 (0.4); 0.0105 (1.4); −0.0004 (39.2); −0.0115 (1.3). I-075 [00265] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4702 (4.3); 9.4478 (4.3); 9.0805 (7.7); 9.0781 (8.4); 9.0733 (8.5); 9.0708 (7.8); 8.6541 (6.4); 8.6468 (5.9); 8.6255 (6.8); 8.6182 (6.8); 8.1621 (8.2); 8.1511 (9.1); 8.1487 (8.6); 8.1224 (7.6); 8.1200 (7.7); 8.0950 (8.5); 8.0833 (7.0); 8.0794 (7.6); 8.0187 (4.8); 7.7975 (4.6); 6.1121 (0.6); 6.0887 (2.9); 6.0659 (4.4); 6.0525 (1.0); 6.0431 (2.8); 6.0195 (0.5); 3.3342 (492.9); 3.3106 (37.3); 2.8321 (0.4); 2.7349 (0.6); 2.7289 (0.9); 2.7229 (0.6); 2.5148 (54.4); 2.5089 (106.7); 2.5029 (141.4); 2.4969 (96.3); 2.4911 (43.4); 2.2788 (0.6); 2.2729 (0.8); 2.2667 (0.6); 1.9099 (0.3); 1.6784 (16.0); 1.6552 (15.8); 1.2357 (0.4); 0.0106 (0.4); −0.0003 (11.5). I-076 [00266] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4493 (2.7); 9.4264 (2.8); 9.0191 (15.6); 9.0029 (16.0); 8.6537 (2.9); 8.6385 (2.9); 8.1081 (4.8); 8.0655 (5.1); 8.0567 (5.1); 8.0542 (5.1); 8.0518 (5.1); 7.6931 (4.2); 7.6769 (7.8): 7.6607 (3.9); 6.0152 (0.4); 5.9917 (1.9): 5.9686 (3.0); 5.9455 (1.9); 5.9225 (0.4); 3.3244 (47.4); 3.3009 (0.4); 2.8971 (0.4); 2.8827 (0.9): 2.8698 (1.0); 2.8591 (1.9); 2.8445 (1.9); 2.8359 (1.1); 2.8215 (0.9); 2.8072 (0.4); 2.7278 (0.4); 2.5138 (22.3); 2.5079 (43.7); 2.5019 (58.0); 2.4959 (39.7); 2.4901 (18.1); 2.2715 (0.4); 2.0756 (3.4); 1.6863 (10.3); 1.6630 (10.1); 0.7195 (0.6); 0.6956 (2.9); 0.6883 (3.5); 0.6805 (3.0); 0.6640 (4.8); 0.6579 (5.3); 0.6433 (5.3); 0.6385 (4.9); 0.6200 (0.8); 0.6058 (0.5); 0.0104 (1.1); −0.0005 (25.6); −0.0114 (0.9). I-077 [00267] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4611 (2.9); 9.4384 (3.0); 9.0257 (15.6); 9.0095 (16.0): 8.5949 (0.8); 8.5810 (2.3); 8.5652 (2.3); 8.5507 (0.8); 8.1146 (5.0); 8.0686 (5.6); 8.0622 (7.1); 7.6973 (4.1); 7.6811 (7.7); 7.6649 (3.9); 6.0306 (0.4); 6.0078 (1.9); 5.9849 (3.1); 5.9619 (1.9); 5.9391 (0.4); 4.3681 (0.4); 4.3542 (0.4); 3.3464 (62.3); 2.7916 (13.4); 2.7758 (13.2); 2.5188 (5.3); 2.5129 (10.5); 2.5070 (13.9); 2.5012 (9.7); 1.6961 (10.5); 1.6729 (10.4); 1.0495 (2.8); 1.0291 (2.7); −0.0004 (1.8). I-078 [00268] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4692 (4.5); 9.4471 (4.7); 9.0839 (7.4); 9.0816 (8.3); 9.0768 (8.4); 9.0744 (7.9); 8.6909 (5.1); 8.6762 (5.2); 8.6561 (6.3); 8.6487 (5.8): 8.6275 (6.6); 8.6201 (6.7); 8.1616 (13.2); 8.1354 (7.3); 8.1330 (7.6); 8.0961 (8.3); 8.0747 (7.6): 6.1097 (0.6); 6.0871 (3.0); 6.0642 (4.7); 6.0415 (3.0); 6.0194 (0.6); 3.3311 (131.5); 2.8894 (0.6); 2.8757 (1.5); 2.8630 (1.9); 2.8514 (2.9); 2.8378 (2.8); 2.8282 (1.7); 2.8139 (1.5); 2.8000 (0.6); 2.5176 (9.3); 2.5117 (18.0); 2.5058 (23.8); 2.4998 (16.4); 2.4940 (7.6); 2.0785 (1.8); 1.6812 (16.0); 1.6580 (15.8); 0.7451 (1.7); 0.7371 (1.4); 0.7199 (6.3); 0.7054 (4.6); 0.6944 (6.2); 0.6820 (3.6); 0.6603 (1.6); 0.6494 (3.4); 0.6360 (8.5); 0.6238 (5.7); 0.6182 (5.0); 0.5975 (1.5); 0.0105 (0.5); −0.0004 (11.2); −0.0113 (0.4). I-079 [00269] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4602 (2.0); 9.4382 (2.0); 9.0835 (3.2); 9.0813 (3.5); 9.0763 (3.6); 9.0740 (3.3); 8.6550 (2.6); 8.6476 (2.5); 8.6263 (3.1); 8.6190 (3.3); 8.6064 (1.6); 8.5904 (1.6); 8.5752 (0.5); 8.1609 (3.4); 8.1391 (3.4); 8.1369 (3.4); 8.1105 (3.4); 8.1082 (3.6); 8.0960 (3.5); 8.0722 (3.2); 6.0848 (1.3); 6.0622 (2.0); 6.0395 (1.3); 3.3279 (9.1); 2.8038 (8.8); 2.7879 (8.6); 2.5190 (4.7); 2.5131 (9.2); 2.5071 (12.1); 2.5012 (8.4); 2.4955 (3.9); 2.0799 (16.0); 1.6899 (7.0); 1.6667 (6.9); −0.0004 (1.8). I-080 [00270] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4738 (2.6); 9.4515 (2.6); 9.0614 (15.7); 9.0451 (16.0); 8.0984 (4.7); 8.0708 (4.5); 8.0366 (4.7); 7.7633 (4.3); 7.7470 (7.9); 7.7307 (4.0); 6.0473 (0.4); 6.0242 (2.0); 6.0013 (3.1); 5.9785 (2.0); 5.9558 (0.4); 3.3150 (88.3); 2.7338 (0.4); 2.7277 (0.5); 2.7214 (0.3); 2.5136 (31.3); 2.5076 (60.7); 2.5016 (80.5); 2.4956 (54.4); 2.4897 (24.4); 2.2774 (0.3); 2.2716 (0.5); 2.2654 (0.4); 2.0734 (4.4); 1.6907 (11.2); 1.6675 (11.1); 1.2348 (0.5); 0.8591 (0.4); −0.0004 (6.3). I-081 [00271] .sup.1H-NMR (300 MHz, d.sub.6-DMSO, ppm): δ = 9.4989 (4.0); 9.4768 (4.1); 9.1264 (6.8); 9.1240 (7.6); 9.1193 (7.7); 9.1168 (7.1); 8.6766 (5.8); 8.6693 (5.5); 8.6481 (6.4); 8.6407 (6.4); 8.1561 (7.6); 8.1537 (7.7); 8.1277 (13.1); 8.1252 (12.5); 8.0883 (7.0); 8.0633 (7.0); 6.0800 (0.6); 6.0571 (2.9); 6.0343 (4.4); 6.0116 (2.9); 5.9887 (0.6); 4.2227 (0.5); 3.3254 (93.3); 2.7350 (0.4); 2.7288 (0.6); 2.7225 (0.4); 2.5147 (36.4); 2.5087 (71.4); 2.5027 (95.0); 2.4967 (65.2); 2.4909 (29.8); 2.2788 (0.4); 2.2726 (0.6); 2.2666 (0.4); 2.0755 (1.2); 1.9102 (0.4); 1.6789 (16.0); 1.6557 (15.8); 1.2333 (0.6); 0.9368 (0.4); 0.9124 (0.9); 0.8875 (0.4); 0.0106 (0.3): −0.0004 (8.7). I-082 [00272] .sup.1H-NMR (400 MHz, d.sub.6-DMSO, ppm): δ = 9.5738 (2.8); 9.5556 (2.8); 8.9608 (15.7); 8.9486 (16.0); 8.3857 (10.2); 8.3048 (4.5); 7.5993 (4.2); 7.5872 (7.8); 7.5750 (4.1); 7.3254 (1.9); 7.3210 (2.9); 7.3042 (8.5); 7.3010 (7.4); 7.2959 (6.4); 7.2943 (6.7); 7.2888 (1.5); 7.2765 (7.6); 7.2724 (2.8); 7.2573 (2.8); 7.2252 (1.5); 7.2211 (2.4); 7.2165 (1.3); 7.2101 (1.1); 7.2037 (2.7); 7.1972 (0.8); 7.1905 (0.7); 7.1865 (1.0); 7.1823 (0.5); 6.0553 (0.4); 6.0381 (2.0); 6.0204 (3.1); 6.0027 (2.0); 5.9853 (0.4); 5.7586 (5.4); 4.1010 (0.4); 4.0611 (10.5); 4.0214 (0.4); 3.3341 (76.9); 2.6782 (0.4); 2.6738 (0.6); 2.6693 (0.4); 2.5272 (1.8); 2.5137 (34.8); 2.5093 (68.8); 2.5048 (88.3); 2.5003 (63.8); 521.2 [M + H].sup.+ 2.4959 (31.1); 2.3361 (0.4); 2.3316 (0.5); 2.3271 (0.4); 1.6465 (11.2); 1.6291 (11.1); 0.0080 (2.1); −0.0002 (55.9): −0.0085 (2.1). I-083 [00273] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4144 (3.0); 9.3962 (3.0); 8.9562 (15.6); 8.9440 (16.0); 8.0879 (5.6); 8.0553 (5.4); 8.0357 (5.6); 7.5986 (4.4); 7.5865 (7.8); 7.5743 (4.2); 7.3259 (1.7); 7.3211 (2.7); 7.3048 (10.4); 7.3003 (14.5); 7.2818 (8.4); 7.2774 (2.7); 7.2624 (2.8); 7.2293 (1.6); 7.2248 (2.5); 7.2197 (1.3); 7.2144 (1.3); 7.2077 (2.8); 7.2011 (0.8); 7.1953 (0.8); 7.1910 (1.1); 7.1864 (0.6); 6.0171 (0.5); 5.9998 (2.2); 5.9820 (3.6); 5.9643 (2.3); 5.9469 (0.5); 5.7569 (12.9); 4.0974 (0.4); 4.0576 (12.8); 4.0178 (0.4); 3.3336 (240.3); 3.1762 (0.7); 3.1631 (0.7); 2.6767 (0.8); 2.6723 487.1 [M + H].sup.+ (1.1); 2.6678 (0.8); 2.5256 (3.5); 2.5121 (74.8); 2.5078 (148.9); 2.5033 (192.1); 2.4988 (138.1); 2.4944 (67.1); 2.3346 (0.8); 2.3301 (1.1); 2.3257 (0.8); 1.6233 (12.8); 1.6059 (12.8); −0.0002 (2.3) I-084 [00274] .sup.1H-NMR (400 MHz, d.sub.6-DMSO, ppm): δ = 9.4554 (2.8); 9.4372 (2.9); 8.9606 (15.6); 8.9484 (16.0); 8.3172 (1.2); 8.2302 (3.9); 8.2265 (7.3); 8.2227 (4.4); 8.1333 (2.8); 8.1285 (7.1); 8.1244 (5.7); 8.1198 (5.8); 8.1160 (6.4); 8.1113 (2.7); 7.6034 (4.1); 7.5912 (7.8); 7.5791 (4.0); 7.3328 (1.1); 7.3274 (2.0); 7.3219 (1.1); 7.3089 (14.8); 7.2919 (7.9); 7.2871 (2.2); 7.2770 (1.3); 7.2722 (2.3); 7.2322 (1.4); 7.2272 (2.2); 7.2213 (1.1); 7.2174 (1.3); 7.2105 (2.4); 7.1991 (0.8); 7.1942 (1.0); 7.1891 (0.6); 6.0352 (0.4); 6.0179 (2.0); 6.0002 (3.2); 5.9824 (2.1); 5.9650 (0.4); 5.7571 (0.4); 4.1077 (0.6); 4.1020 (0.5); 4.0947 (0.7); 4.0816 (0.4); 4.0625 (10.5); 4.0217 (0.4); 3.3335 (117.6); 3.3110 (32.6); 497.1 [M + H].sup.+ 3.1761 (3.5); 3.1630 (3.4); 2.6766 (0.5); 2.6720 (0.7); 2.6676 (0.5); 2.5255 (2.3); 2.5207 (3.6); 2.5120 (44.6); 2.5076 (89.5); 2.5031 (116.1); 2.4985 (83.7); 2.4941 (40.5); 2.3344 (0.5); 2.3298 (0.7); 2.3254 (0.5); 1.6267 (11.5); 1.6093 (11.4); 0.0080 (2.3); −0.0002 (65.1); −0.0085 (2.3) I-085 [00275] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.9631 (10.9); 8.9509 (11.2); 8.7798 (2.0); 8.7606 (2.0); 7.6072 (2.9); 7.5950 (5.5); 7.5829 (2.8); 7.3356 (0.4); 7.3293 (1.0); 7.3145 (16.0); 7.3088 (6.6); 7.2984 (6.2); 7.2931 (1.2); 7.2838 (0.8); 7.2784 (1.3); 7.2395 (1.0); 7.2337 (1.4); 7.2258 (1.2); 7.2179 (1.6); 7.2040 (6.5); 6.0139 (0.3); 5.9967 (1.6); 5.9785 (2.1); 5.9603 (1.6); 5.9430 (0.3); 5.7559 (7.4); 4.0986 (0.4); 4.0595 (8.0); 4.0182 (0.5); 4.0028 (15.4); 3.3436 (304.1); 3.1762 (0.4); 3.1631 (0.3); 2.6769 (0.5); 2.6725 (0.7); 2.6681 (0.5); 2.5259 (2.1); 2.5211 (3.3); 2.5124 (43.4); 2.5081 (88.4); 2.5035 (115.9); 2.4990 (84.2); 2.4946 (41.4); 2.3349 (0.5); 2.3303 (0.7); 457.2 [M + H].sup.+ 2.3259 (0.5); 1.5663 (8.9); 1.5490 (8.9); −0.0002 (0.6) I-086 [00276] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5544 (2.7); 9.5362 (2.8); 8.9341 (15.6); 8.9219 (16.0); 8.3649 (9.9); 8.3163 (2.3); 8.3034 (4.3); 7.5850 (4.0); 7.5728 (7.6); 7.5607 (3.9); 7.4164 (0.6); 7.3996 (1.3); 7.3949 (1.3); 7.3783 (2.7); 7.3613 (1.4); 7.3577 (1.6); 7.3406 (0.7); 7.1268 (0.5); 7.1149 (3.9); 7.1064 (0.9); 7.0955 (5.6); 7.0755 (3.3); 7.0641 (0.4); 6.0287 (0.4); 6.0122 (2.0); 5.9945 (3.1); 5.9767 (2.1); 5.9600 (0.5); 5.7565 (4.1); 4.1007 (10.4); 3.3296 (1053.5); 2.6803 (2.6); 2.6759 (5.3); 2.6714 (7.3); 2.6668 (5.4); 2.5859 (0.7); 2.5248 (22.7); 2.5201 (36.3); 2.5114 (451.0); 2.5069 (908.2); 2.5024 (1177.9); 2.4978 (844.6); 2.4933 (405.1); 2.3382 (2.5); 2.3338 (5.1); 2.3293 (7.1); 2.3247 (5.2); 2.2976 (0.6); 1.6331 (11.1); 1.6157 (11.1); 1.2383 (0.6); 1.2105 (0.4); 1.1935 (0.3); 0.1462 (1.7); 0.0081 (16.5); −0.0001 557.1 [M + H].sup.+ (486.6); −0.0084 (16.8); −0.1495 (1.8) I-087 [00277] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4219 (3.1); 9.4042 (3.2); 8.9705 (15.6); 8.9583 (16.0); 8.0960 (5.7); 8.0586 (5.5); 8.0420 (5.8); 7.6153 (4.1); 7.6032 (7.8); 7.5910 (4.0); 7.1074 (0.7); 7.1015 (1.4); 7.0958 (1.0); 7.0839 (1.3); 7.0781 (2.8); 7.0723 (2.2); 7.0611 (1.4); 7.0485 (5.2); 7.0299 (5.0); 7.0144 (0.7); 6.0026 (0.5); 5.9853 (2.4); 5.9678 (3.7); 5.9502 (2.4); 5.9328 (0.5); 5.7584 (5.4); 4.1282 (15.6); 3.3304 (38.5); 2.6782 (0.5); 2.6736 (0.7); 2.6691 (0.5); 2.5269 (2.2); 2.5133 (42.4); 2.5091 (83.6); 2.5046 (107.9); 2.5001 (77.5); 2.4958 (37.5); 2.3359 (0.5); 2.3313 (0.6); 2.3269 (0.5); 1.6448 (13.0); 1.6274 (12.8); 1.3971 (2.3); −0.0001 (1.6) 522.8 [M + H].sup.+ I-088 [00278] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5139 (2.0); 9.4960 (2.1); 8.8752 (10.0); 8.8631 (10.2); 8.5465 (0.4); 8.4725 (7.8); 8.3116 (3.4); 7.4533 (2.6); 7.4412 (4.9); 7.4291 (2.6); 6.0870 (0.3); 6.0697 (1.5); 6.0522 (2.4); 6.0346 (1.6); 6.0173 (0.3); 5.7577 (0.9); 3.6479 (1.3); 3.5691 (14.3); 3.4917 (1.0); 3.4731 (1.4); 3.4624 (1.6); 2.7451 (16.0); 2.6770 (0.5); 2.6726 (0.7); 2.6682 (0.5); 2.5260 (1.8); 2.5124 (42.9); 2.5082 (85.7); 2.5037 (110.9); 2.4992 (81.0); 2.4949 (40.2); 2.3351 (0.5); 2.3305 (0.7); 2.3261 (0.5); 1.6202 (8.6); 1.6029 (8.5); 1.5535 (0.4); 1.5368 (0.4); −0.0001 (2.4) 459.7 [M + H].sup.+ I-089 [00279] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4541 (0.5); 9.4364 (0.5); 8.9872 (2.8); 8.9751 (2.9); 8.2905 (1.0); 8.1719 (0.9); 8.1320 (0.9); 7.6283 (0.8); 7.6162 (1.4); 7.6040 (0.7); 6.0261 (0.4); 6.0086 (0.6); 5.9910 (0.4); 3.3291 (73.3); 3.3075 (0.5); 3.2129 (6.9); 2.6761 (0.3); 2.6716 (0.4); 2.6670 (0.3); 2.5250 (1.4); 2.5115 (28.7); 2.5072 (56.8); 2.5026 (73.1); 2.4981 (52.9); 2.4937 (25.8); 2.3294 (0.4); 2.0751 (0.6); 1.6496 (2.0); 1.6322 (2.0); 1.5033 (0.7); 1.3386 (16.0); −0.0002 (0.4) 570.1 [M + H].sup.+ I-090 [00280] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2572 (2.8); 9.2395 (2.8); 8.8833 (0.3); 8.8708 (0.5); 8.8557 (15.6); 8.8436 (16.0); 8.3151 (1.1); 7.9756 (4.0); 7.9716 (6.3); 7.9677 (4.3); 7.7714 (4.4); 7.7550 (4.5); 7.7524 (4.5); 7.4429 (4.0); 7.4308 (7.6); 7.4187 (4.0); 6.0187 (0.5); 6.0011 (2.1); 5.9835 (3.3); 5.9660 (2.2); 5.9483 (0.4); 5.7555 (1.0); 5.7405 (8.6); 3.6476 (0.4); 3.5684 (0.5); 3.4962 (0.4); 3.4873 (0.4); 3.4731 (0.5); 3.4614 (0.5); 3.3392 (885.9); 2.6765 (2.7); 2.6720 (3.7); 2.6673 (2.7); 2.5254 (11.3); 2.5205 (18.0); 2.5119 (227.9); 2.5075 (459.8); 2.5030 (598.5); 2.4984 (429.9); 2.4940 (207.1); 2.3385 (1.2); 2.3343 428.2 [M + H].sup.+ (2.5); 2.3298 (3.5); 2.3252 (2.5); 2.3208 (1.2); 1.5849 (12.0); 1.5675 (11.9); 1.2338 (1.0); 1.1659 (0.4); −0.0001 (4.9) I-091 [00281] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5824 (1.3); 9.5649 (1.3); 8.9941 (7.3); 8.9820 (7.4); 8.4008 (4.7); 8.3164 (2.7); 7.6360 (1.9); 7.6238 (3.6); 7.6117 (1.9); 6.0600 (1.0); 6.0427 (1.6); 6.0254 (1.0); 3.6018 (0.5); 3.3250 (116.7); 3.2721 (15.9); 2.9270 (0.5); 2.9147 (0.5); 2.6758 (1.4); 2.6713 (1.9); 2.6668 (1.4); 2.5248 (5.8); 2.5200 (9.2); 2.5113 (119.5); 2.5069 (242.1); 2.5023 (314.9); 2.4978 (225.1); 2.4933 (107.2); 2.3337 (1.4); 2.3291 (1.9); 2.3246 (1.4); 2.2610 (16.0); 1.9089 (0.4); 1.7607 (0.6); 1.6950 (5.3); 1.6776 (5.3); 1.5252 (0.4); 1.5083 (0.4); 1.1819 (0.4); −0.0001 (1.6) 501.7 [M + H].sup.+ I-092 [00282] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3508 (3.1); 9.3331 (3.2); 8.8715 (15.6); 8.8594 (16.0); 8.3091 (6.0); 8.1655 (6.2); 8.1555 (6.4); 7.4527 (4.0); 7.4406 (7.7); 7.4285 (4.0); 6.2397 (2.4); 6.2269 (2.5); 6.2154 (0.9); 6.0473 (0.5); 6.0298 (2.4); 6.0123 (3.7); 5.9948 (2.4); 5.9771 (0.6); 5.7570 (2.8); 3.6473 (1.5); 3.5684 (3.4); 3.3285 (183.9); 2.9037 (0.4); 2.7483 (14.5); 2.7359 (14.5); 2.6761 (1.7); 2.6716 (2.3); 2.6674 (1.7); 2.5248 (7.3); 2.5112 (146.6); 2.5071 (287.0); 2.5026 (369.8); 2.4981 (267.8); 2.4939 (131.9); 2.3338 (1.6); 2.3294 (2.2); 2.3250 (1.6); 1.6166 (0.4); 1.5943 (13.2): 1.5770 (13.1); −0.0001 (1.3) 471.6 [M + H].sup.+ I-093 [00283] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3405 (3.1); 9.3226 (3.0); 8.8857 (0.9); 8.8827 (0.9); 8.8737 (1.1); 8.8705 (1.1); 8.8591 (15.5); 8.8470 (16.0); 8.3140 (5.7); 8.2930 (0.4); 8.2827 (0.4); 8.1629 (10.2); 8.1370 (0.6); 8.1178 (0.5); 7.4683 (0.5); 7.4449 (4.1); 7.4329 (7.7); 7.4208 (4.0); 6.0389 (0.5); 6.0216 (2.2); 6.0041 (3.5); 5.9864 (2.3); 5.9693 (0.5); 5.7440 (9.0); 3.7001 (0.3); 3.6471 (0.4); 3.3265 (123.5); 2.6760 (1.4); 2.6714 (1.9); 2.6669 (1.4); 2.5249 (5.8); 2.5113 (125.4); 2.5070 (247.9); 2.5025 (318.5); 2.4980 (231.3); 2.4937 (113.8); 2.3338 (1.4); 2.3293 (2.0); 2.3247 (1.4); 2.0864 (1.4); 1.5917 (12.9); 1.5744 457.5 [M + H].sup.+ (12.8); 1.2342 (0.8); −0.0002 (1.3) I-094 [00284] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1859 (2.5); 9.1680 (2.3); 8.8858 (1.3); 8.8832 (1.4); 8.8737 (1.5); 8.8711 (1.5); 8.8564 (11.8); 8.8444 (11.9); 8.3161 (0.9); 8.0246 (2.3); 8.0202 (4.9); 8.0162 (6.0); 8.0080 (16.0); 8.0039 (8.9); 7.9881 (1.5); 7.9838 (1.2); 7.9767 (1.6); 7.9724 (1.2); 7.4805 (0.4); 7.4699 (0.7); 7.4579 (0.4); 7.4453 (3.2); 7.4332 (5.9); 7.4211 (3.1); 6.6837 (0.3); 6.0031 (0.5); 5.9858 (1.8); 5.9762 (0.9); 5.9682 (2.7); 5.9587 (0.6); 5.9506 (1.8); 5.9330 (0.4); 5.7397 (6.7); 4.6238 (0.5); 3.7246 (0.4); 3.7180 (0.5); 3.7136 (0.9); 3.7097 (0.7); 3.7018 (1.0); 3.6997 (1.1); 3.6801 (1.0); 3.6781 (0.9); 467.3 [M + H].sup.+ 3.6703 (0.6); 3.6661 (0.8); 3.6616 (0.4); 3.6551 (0.4); 3.6472 (1.8); 3.5682 (0.8); 3.5099 (0.5); 3.4964 (0.8); 3.4847 (0.6); 3.4728 (0.9); 3.4613 (0.8); 3.3261 (186.6); 2.6757 (1.8); 2.6712 (2.4); 2.6666 (1.8); 2.5246 (7.6); 2.5111 (155.0); 2.5068 (307.5); 2.5022 (402.5); 2.4977 (297.0); 2.4933 (147.5); 2.3336 (1.8); 2.3290 (2.5); 2.3245 (1.8); 1.5680 (10.4); 1.5507 (10.2); 1.3377 (0.3); 1.2347 (0.7); 0.0079 (1.9); −0.0002 (53.3); −0.0085 (2.2); −0.0636 (1.1) I-095 [00285] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3288 (0.3); 9.2572 (3.3); 9.2396 (3.1); 8.9445 (0.4); 8.9325 (0.4); 8.9282 (0.4); 8.9242 (0.4); 8.8833 (1.6); 8.8800 (1.7); 8.8713 (1.8); 8.8677 (1.8); 8.8554 (16.0); 8.8433 (16.0); 8.3161 (2.6); 8.1812 (0.4); 8.1080 (4.6); 8.1042 (7.2); 8.1006 (4.5); 8.0841 (0.7); 8.0790 (0.8); 8.0745 (0.8); 8.0557 (0.4); 8.0502 (0.4); 8.0392 (0.4); 8.0248 (0.4); 7.8755 (5.4); 7.8109 (0.5); 7.7791 (4.8); 7.7448 (0.7); 7.4971 (0.4); 7.4934 (0.3); 7.4793 (0.6); 7.4671 (0.7); 7.4555 (0.7); 7.4428 (4.2); 7.4307 (7.8); 7.4186 (4.1); 6.3516 (0.4); 5.9988 (2.6); 5.9814 (3.8); 5.9639 (2.6); 5.9465 (0.8); 473.8 [M + H].sup.+ 5.9296 (0.3); 5.7411 (9.1); 4.6367 (0.5); 4.6243 (0.8); 4.6125 (0.4); 4.2087 (0.3); 3.8600 (0.3); 3.7294 (0.6); 3.7246 (0.7); 3.7136 (1.4); 3.7096 (1.4); 3.6997 (1.6); 3.6801 (1.7); 3.6703 (1.1); 3.6662 (1.3); 3.6615 (0.7); 3.6551 (0.8); 3.6471 (4.8); 3.6280 (0.4); 3.6218 (0.4); 3.5982 (0.5); 3.5844 (0.4); 3.5682 (0.8); 3.5570 (0.4); 3.5510 (0.3); 3.5421 (0.3); 3.5097 (0.9); 3.4962 (1.3); 3.4862 (1.1); 3.4728 (1.6); 3.4610 (1.4); 3.4498 (0.8); 3.4129 (0.6); 3.3273 (938.9); 2.8915 (0.7); 2.7311 (0.7); 2.6897 (0.8); 2.6757 (5.8); 2.6711 (8.0); 2.6668 (6.0); 2.5727 (1.0); 2.5246 (25.0); 2.5110 (522.0); 2.5067 (1017.6); 2.5022 (1314.9); 2.4976 (968.6); 2.4933 (480.5); 2.3876 (0.3); 2.3335 (5.9); 2.3291 (7.9); 2.3245 (5.8); 1.6542 (0.6); 1.6465 (0.6); 1.6422 (0.6); 1.6382 (0.6); 1.6271 (0.8); 1.5825 (14.0); 1.5652 (14.0); 1.5204 (0.8); 1.4824 (0.6); 1.4447 (0.6); 1.4389 (0.7); 1.4295 (0.7); 1.4193 (0.7); 1.3954 (1.0); 1.3751 (0.9); 1.3382 (0.8); 1.3106 (0.6); 1.2909 (0.7); 1.2589 (0.6); 1.2347(1.5); 1.1676 (0.4); 1.1405 (0.4); 1.1270 (0.5); 1.1121 (0.4); 1.1012(0.5); 1.0919 (0.4); 1.0821 (0.4); 1.0570 (0.3); 1.0192 (0.3); 1.0035 (0.3); 0.9734 (0.4); 0.9190 (0.3); 0.8760 (0.4); 0.8539 (0.5); 0.8352 (0.5); 0.8326 (0.5); 0.8098 (0.4); 0.1459 (0.6); 0.0079 (5.8); −0.0002 (163.7); −0.0085 (6.9); −0.1499 (0.7) I-096 [00286] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.0900 (1.2); 9.6042 (0.6); 9.5878 (0.6); 9.0206 (1.0); 9.0167 (1.0); 8.5486 (0.7); 8.5431 (0.6); 8.5271 (0.7); 8.5215 (0.7); 8.4790 (2.0); 8.3284 (0.9); 7.9622 (1.0); 7.9608 (0.9); 7.9406 (0.9); 7.9391 (0.9); 6.1166 (0.4); 6.0997 (0.6); 6.0825 (0.4); 3.3278 (67.0); 2.6898 (0.4); 2.6757 (0.4); 2.6714 (0.6); 2.6670 (0.4); 2.5247 (1.8); 2.5112 (35.9); 2.5069 (69.7); 2.5024 (89.7); 2.4979 (65.3); 2.4935 (31.8); 2.3337 (0.4); 2.3294 (0.5); 2.3247 (0.4); 2.0749 (0.9); 1.6582 (2.1); 1.6408 (2.0); 1.4301 (16.0); −0.0002 (5.7) 570.3 [M + H].sup.+ I-097 [00287] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0740 (2.9); 9.0559 (2.9); 8.8797 (0.5); 8.8754 (0.5); 8.8676 (0.6); 8.8633 (0.8); 8.8537 (15.6); 8.8417 (16.0); 8.3171 (0.4); 7.5039 (8.5); 7.5005 (8.7); 7.4751 (0.6); 7.4715 (0.6); 7.4591 (0.6); 7.4400 (4.1); 7.4279 (7.6); 7.4158 (4.0); 7.2660 (4.3); 6.0095 (0.5); 5.9925 (2.1); 5.9749 (3.3); 5.9572 (2.2); 5.9397 (0.5); 5.7238 (8.5); 3.6475 (0.8); 3.3269 (46.0); 2.6763 (0.8); 2.6717 (1.0); 2.6671 (0.8); 2.6625 (0.4); 2.5251 (3.0); 2.5117 (67.7); 2.5073 (134.5); 2.5027 (174.7); 2.4982 (127.4); 2.4937 (62.3); 2.3341 (0.8); 2.3296 (1.1); 2.3250 (0.8); 2.0630 (0.6); 2.0506 (1.3); 2.0420 (1.4); 2.0383 (1.1); 2.0296 (2.6); 2.0171 (1.6); 433.9 [M + H].sup.+ 2.0088 (1.4); 1.9962 (0.8); 1.5840 (11.9); 1.5666 (11.8); 1.0461 (1.5); 1.0349 (4.2); 1.0294 (4.6); 1.0256 (2.5); 1.0189 (2.6); 1.0140 (4.5); 1.0085 (4.5); 0.9981 (2.0); 0.9808 (0.4); 0.7944 (1.8); 0.7837 (4.9); 0.7786 (4.9); 0.7714 (4.8); 0.7663 (5.4); 0.7548 (1.8); −0.0001 (3.0) I-098 [00288] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.0884 (1.3); 9.3024 (0.6); 9.2856 (0.6); 9.0134 (1.0); 9.0094 (1.0); 8.5470 (0.7); 8.5415 (0.6); 8.5255 (0.7); 8.5200 (0.7); 8.0371 (1.3); 8.0330 (1.1); 8.0158 (3.2); 8.0115 (2.3); 7.9548 (1.0); 7.9330 (0.9); 6.0471 (0.4); 6.0305 (0.6); 6.0131 (0.4); 3.3298 (96.8); 2.6757 (0.4); 2.6713 (0.6); 2.6669 (0.4); 2.5068 (74.4); 2.5024 (95.2); 2.4979 (71.0); 2.3335 (0.4); 2.3291 (0.6); 2.3247 (0.4); 1.6094 (2.1); 1.5921 (2.1); 1.4394 (16.0); −0.0002 (1.5) 592.1 [M + H].sup.+ I-099 [00289] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2694 (1.9); 9.2516 (1.9); 8.8690 (8.8); 8.8570 (9.1); 7.9730 (2.5); 7.9689 (4.1); 7.9653 (3.0); 7.9531 (2.5); 7.7706 (3.0); 7.7503 (2.9); 7.7482 (3.0); 7.4509 (2.3); 7.4388 (4.4); 7.4267 (2.3); 6.2402 (1.3); 6.2277 (1.4); 6.0110 (1.3); 5.9936 (2.1); 5.9760 (1.4); 5.7571 (1.2); 3.3303 (54.4); 2.8915 (15.6); 2.7486 (7.4); 2.7328 (15.6); 2.7319 (16.0); 2.6765 (0.5); 2.6720 (0.6); 2.6674 (0.5); 2.5501 (0.4); 2.5075 (78.8); 2.5031 (103.7); 2.4986 (79.8); 2.3344 (0.4); 2.3299 (0.6); 2.3256 (0.5); 1.5881 (7.4); 1.5708 (7.4); −0.0001 (2.6) 441.8 [M + H].sup.+ I-100 [00290] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1983 (2.4); 9.1802 (2.5); 8.8948 (0.3); 8.8692 (13.0); 8.8572 (13.4); 8.3167 (0.5); 8.0766 (0.4); 8.0253 (2.9); 8.0210 (6.0); 8.0168 (5.6); 8.0037 (16.0); 7.9994 (10.2); 7.9829 (0.3); 7.9780 (0.4); 7.4532 (3.5); 7.4411 (6.4); 7.4290 (3.4); 6.2531 (0.7); 6.2409 (2.3); 6.2282 (2.3); 6.2156 (0.7); 6.0117 (0.4); 5.9939 (1.8); 5.9764 (2.8); 5.9588 (1.9); 5.9420 (0.4); 5.7570 (0.6); 3.3265 (127.7); 2.9024 (0.5); 2.7469 (12.6); 2.7343 (12.6); 2.7067 (0.5); 2.6964 (0.4); 2.6756 (1.3); 2.6712 (1.7); 2.6667 (1.3); 2.5246 (5.1); 2.5111 (113.2); 2.5068 (220.3); 2.5023 (283.1); 2.4977 (207.1); 2.4933 481.7 [M + H].sup.+ (101.9); 2.3335 (1.3); 2.3291 (1.7); 2.3246 (1.3); 2.0751 (7.5); 1.8299 (0.5); 1.5940(0.4); 1.5707 (10.0); 1.5534 (10.0); 1.4126 (0.3); 1.3952 (0.3); −0.0002 (4.6) I-101 [00291] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0920 (3.0); 9.0739 (3.0); 8.8666 (15.6); 8.8545 (16.0); 7.4969 (10.0); 7.4935 (9.5); 7.4483 (4.1); 7.4363 (7.6); 7.4242 (4.0); 7.2693 (4.5); 6.2355 (0.9); 6.2236 (2.8); 6.2108 (2.8); 6.1984 (0.8); 6.0160 (0.5); 5.9990 (2.2); 5.9814 (3.4); 5.9638 (2.2); 5.9462 (0.4); 3.3328 (88.9); 2.7472 (15.2); 2.7346 (15.1); 2.6765 (0.8); 2.6719 (1.0); 2.6674 (0.8); 2.5253 (3.5); 2.5118 (66.7); 2.5075 (129.1); 2.5030 (166.8); 2.4985 (123.2); 2.4941 (60.9); 2.3342 (0.8); 2.3298 (1.0); 2.3254 (0.7); 2.0762 (1.0); 2.0623 (0.6); 2.0497 (1.3); 2.0413 (1.4); 2.0289 (2.6); 2.0164 (1.5); 2.0081 (1.4); 1.9954 (0.7); 1.5863 (12.0); 1.5689 (11.9); 1.0459 (1.5); 448.3 [M + H].sup.+ 1.0347 (4.3); 1.0292 (4.6); 1.0187 (2.5); 1.0138 (4.4); 1.0083 (4.4); 0.9980 (1.7); 0.7929 (1.8); 0.7823 (5.0); 0.7772 (5.0); 0.7700 (4.7); 0.7649 (5.2); 0.7534 (1.4); 0.1459 (0.5); 0.0078 (5.2); −0.0002 (119.8); −0.0085 (4.7); −0.1495 (0.5) I-102 [00292] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.0886 (1.3); 9.4491 (0.6); 9.4325 (0.6); 9.0180 (1.0); 9.0163 (1.0); 9.0126 (1.0); 9.0108 (1.0); 8.5476 (0.7); 8.5420 (0.7); 8.5260 (0.8); 8.5204 (0.8); 8.3233 (1.0); 8.1796 (1.0); 8.1632 (1.0); 7.9597 (1.0); 7.9581 (1.0); 7.9382 (0.9); 7.9364 (0.9); 6.0822 (0.4); 6.0651 (0.6); 6.0479 (0.4); 3.3257 (9.6); 2.5252 (0.7); 2.5118 (15.0); 2.5074 (29.8); 2.5029 (39.0); 2.4983 (28.5); 2.4939 (14.0); 1.6342 (2.1); 1.6168 (2.1); 1.4355 (16.0); −0.0002 (0.9) 581.8 [M + H].sup.+ I-103 [00293] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2736 (3.3); 9.2557 (3.3); 8.9577 (0.4); 8.9459 (0.4); 8.8689 (15.6); 8.8569 (16.0); 8.3181 (0.8); 8.1014 (7.3); 8.0979 (4.7); 7.8788 (5.2); 7.7745 (5.2); 7.4516 (4.2); 7.4395 (7.7); 7.4274 (4.0); 6.2443 (2.2); 6.2322 (2.2); 6.0255 (0.5); 6.0077 (2.4); 5.9902 (3.7); 5.9726 (2.4); 5.9550 (0.6); 3.5683 (0.4); 3.3336 (227.8); 2.9476 (0.4); 2.9414 (0.6); 2.7471 (12.6); 2.7353 (12.6); 2.6760 (2.0); 2.6717 (2.7); 2.6673 (2.1); 2.5249 (8.7); 2.5072 (325.4); 2.5027 (422.0); 2.4983 (317.7); 2.3339 (1.9); 2.3296 (2.5); 2.3252 (1.8); 2.0757 (2.0); 1.6321 (0.4); 1.6151 (0.4); 1.5854 (13.1); 1.5681 487.7 [M + H].sup.+ (13.0); 1.4663 (0.4); 1.4502 (0.4); 1.4330 (2.2); 1.2584 (0.6); 1.2427 (0.7); 0.1461 (1.2); 0.0079 (11.3); −0.0001 (262.6); −0.0083 (12.1); −0.1495 (1.1) I-104 [00294] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5417 (4.1); 9.5242 (4.3); 9.5022 (0.3); 8.9353 (7.2); 8.9314 (7.2); 8.9298 (6.8); 8.9100 (0.3); 8.9040 (0.4); 8.5178 (14.7); 8.4898 (0.4); 8.4489 (5.7); 8.4433 (5.6); 8.4272 (5.8); 8.4216 (5.9); 8.3894 (0.4); 8.3287 (6.6); 8.3186 (2.2); 7.8283 (6.7); 7.8270 (6.7); 7.8067 (6.3); 7.8052 (6.3); 6.1428 (0.8); 6.1258 (3.2); 6.1085 (4.9); 6.0911 (3.3); 6.0741 (1.0); 6.0153 (0.7); 5.9984 (0.8); 5.9820 (0.8); 5.7582 (6.8); 3.7995 (0.4); 3.7146 (0.5); 3.7107 (0.4); 3.7009 (0.6); 3.6803 (0.6); 3.6702 (0.4); 3.6660 (0.5); 3.6616 (0.3); 3.6472 (1.1); 3.5684 (5.1); 3.5032 (1.0); 3.4906 (1.3); 3.4732 (1.6); 3.4607 (1.9); 3.3916 (58.3); 2.6897 (1.2); 2.6762 (2.8); 2.6718 (3.8); 2.6673 (2.9); 2.5253 (11.6); 2.5203 (19.3); 2.5118 (241.8); 2.5074 (484.8); 2.5028 (637.4); 2.4983 (473.0); 2.4938 (234.6); 2.3341 (2.9); 2.3297 (3.9); 2.3252 (2.9); 1.6168 (16.0); 1.5995 (15.8); 1.2757 (0.4); 1.2603 469.8 [M + H].sup.+ (0.6); 1.2439 (0.5); 0.1459 (1.8); 0.0080 (15.3); −0.0001 (431.6); −0.0084 (17.5); −0.1496 (1.8) I-105 [00295] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2394 (2.8); 9.2217 (2.8); 8.8596 (15.7); 8.8475 (16.0); 8.3176 (2.0); 8.1623 (4.2); 8.1590 (7.3); 8.1557 (4.4); 8.0741 (1.8); 8.0709 (2.0); 8.0678 (2.1); 8.0648 (1.8); 8.0532 (1.9); 8.0500 (2.1); 8.0469 (2.1); 8.0439 (1.8); 7.9842 (1.9); 7.9805 (2.1); 7.9780 (2.0); 7.9745 (1.7); 7.9605 (2.0); 7.9568 (2.3); 7.9507 (1.7); 7.4465 (4.1); 7.4344 (7.7); 7.4223 (4.0); 6.0303 (0.5); 6.0139 (2.0); 5.9962 (3.5); 5.9787 (2.2); 5.9615 (0.5); 5.7578 (6.2); 5.7501 (8.4); 3.7146 (0.4); 3.7003 (0.4); 3.6779 (0.4); 3.6655 (0.4); 3.6470 (1.5); 3.5682 (1.0); 3.4960 (0.4); 3.4840 (0.3); 3.4726 (0.5); 3.4607 (0.5); 3.3326 (831.4); 2.6803 (1.9); 2.6759 (4.0); 2.6714 (5.3); 2.6669 (3.9); 2.5248 (17.2); 352.9 [M + H].sup.+ 2.5114 (329.8); 2.5070 (655.1); 2.5024 (858.4); 2.4978 (630.7); 2.4934 (308.9); 2.3338 (3.7); 2.3292 (5.2); 2.3247 (3.8); 2.3205 (1.7); 2.0754 (2.0); 1.6148 (0.3); 1.5873 (11.6); 1.5700 (11.6); 1.4325 (0.9); 0.1459 (2.0); 0.0223 (0.5); 0.0080 (19.0); −0.0001 (512.3); −0.0084 (18.6); −0.1496 (2.0) I-106 [00296] 680.1 [M + H].sup.+ I-107 [00297] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1818 (1.7); 9.1640 (1.8); 8.4948 (3.0); 8.4907 (3.0); 8.0475 (1.9); 8.0418 (2.0); 8.0251 (16.0); 7.7410 (2.9); 7.7197 (2.6); 6.0556 (1.2); 6.0380 (1.8); 6.0205 (1.2); 5.8208 (4.6); 5.7564 (13.2); 3.6111 (1.9); 3.3261 (81.4); 2.6756 (0.6); 2.6712 (0.9); 2.6668 (0.7); 2.5244 (2.8); 2.5067 (106.4); 2.5023 (138.8); 2.4978 (103.3); 2.3335 (0.6); 2.3292 (0.9); 2.3248 (0.6); 2.0748 (0.3); 1.9295 (0.4); 1.7687 (0.5); 1.5773 (6.3); 1.5600 (6.2); 0.0080 (2.6); −0.0001 (67.4); −0.0084 (2.8) 579.2 [M + H].sup.+ I-108 [00298] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1861 (3.2); 9.1679 (3.1); 8.8952 (0.4); 8.8833 (0.9); 8.8713 (0.9); 8.8566 (15.8); 8.8446 (16.0); 8.3164 (1.1); 7.9824 (4.5); 7.9785 (7.6); 7.9747 (5.2); 7.9457 (0.5); 7.9162 (4.3); 7.9116 (7.9); 7.9071 (4.6); 7.8903 (0.5); 7.8757 (5.2); 7.8718 (6.9); 7.8676 (4.2); 7.8461 (0.4); 7.4898 (0.3); 7.4689 (0.5); 7.4453 (4.2); 7.4332 (7.8); 7.4211 (4.1); 7.3043 (0.3); 7.2850 (0.7); 7.2603 (0.7); 6.3514 (0.4); 6.0042 (0.6); 5.9882 (2.4); 5.9706 (3.7); 5.9529 (2.4); 5.9351 (0.5); 5.7396 (9.3); 4.6236 (0.4); 3.8095 (0.6); 3.7247 (0.4); 3.7130 (0.6); 3.7000 (0.7); 3.6803 (0.7); 3.6700 (0.5); 423.8 [M + H].sup.+ 3.6666 (0.6); 3.6471 (1.6); 3.5075 (0.4); 3.4958 (0.5); 3.4843 (0.4); 3.4722 (0.6); 3.4609 (0.6); 3.3264 (427.0); 2.6756 (3.0); 2.6711 (4.1); 2.6666 (3.1); 2.5244 (14.5); 2.5109 (252.2); 2.5066 (493.4); 2.5021 (640.6); 2.4976 (468.4); 2.4933 (230.4); 2.3334 (2.8); 2.3289 (3.8); 2.3245 (2.8); 1.9888 (0.3); 1.7896 (0.5); 1.6499 (0.9); 1.6135 (0.4); 1.5700 (13.4); 1.5527 (13.1); 1.4328 (1.5); 1.2981 (0.4); 1.2586 (0.7); 1.2339 (1.2); 1.1054 (0.3); 0.1460 (1.1); 0.0080 (8.9); −0.0002 (236.7); −0.0084 (9.0); −0.1495 (1.0) I-109 [00299] .sup.1H-NMR (400.2 MHz, d6-DMSO): δ = 9.4435 (2.1); 9.4251 (2.2); 8.9355 (12.9); 8.9234 (13.2); 8.3950 (0.4); 8.3168 (1.1); 8.2856 (0.4); 8.2129 (3.0); 8.2090 (5.6); 8.2053 (3.4); 8.1298 (2.7); 8.1251 (5.1); 8.1209 (3.5); 8.1039 (3.7); 8.0999 (4.6); 8.0953 (2.5); 7.5908 (3.3); 7.5786 (6.2); 7.5665 (3.2); 7.4238 (0.4); 7.4073 (1.1); 7.4031 (1.0); 7.3862 (2.0); 7.3690 (1.0); 7.3654 (1.2); 7.3485 (0.6); 7.1398 (0.5); 7.1290 (3.0); 7.1196 (0.8); 7.1095 (4.4); 7.0990 (0.8); 7.0898 (2.5); 7.0781 (0.4); 6.0101 (0.3); 5.9935 (1.5); 5.9758 (2.3); 5.9580 (1.5); 5.7571 (16.0); 4.1025 (7.7); 4.0728 (0.6); 3.3732 (2.8); 3.3612 (0.8); 3.3271 (306.5); 3.3106 (25.7); 3.1312 (0.5); 3.1127 (0.4); 2.6801 (1.4); 2.6756 (2.8); 2.6711 (3.9); 2.6665 (2.9); 2.6619 (1.4); 2.5246 (11.9); 2.5198 (19.2); 2.5111 533.1 [M + H].sup.+ (234.8); 2.5067 (474.9); 2.5021 (617.5); 2.4975 (445.0); 2.4930 (214.2); 2.3379 (1.2); 2.3335 (2.7); 2.3289 (3.7); 2.3244 (2.7); 1.6167 (8.4); 1.5993 (8.3); 1.2508 (0.5); 1.2321 (1.0); 1.2134 (0.4); 0.1458 (1.0); 0.0080 (8.3); −0.0002 (254.0); −0.0085 (8.9); −0.1496 (0.9) I-110 [00300] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4572 (3.0); 9.4394 (3.0); 8.9705 (15.6); 8.9583 (16.0); 8.2384 (4.2); 8.2347 (7.5); 8.2310 (4.6); 8.1374 (3.2); 8.1327 (7.2); 8.1286 (5.4); 8.1216 (5.6); 8.1178 (6.4); 8.1132 (3.0); 7.6164 (4.2); 7.6042 (7.8); 7.5921 (4.0); 7.1173 (0.7); 7.1115 (1.3); 7.1057 (1.0); 7.0939 (1.2); 7.0881 (2.7); 7.0822 (2.4); 7.0756 (1.1); 7.0649 (4.9); 7.0600 (5.0); 7.0438 (4.8); 7.0283 (0.7); 6.0236 (0.4); 6.0063 (2.1); 5.9887 (3.4); 5.9711 (2.2); 5.9540 (0.5); 5.7571 (2.3); 4.1335 (14.1); 3.3759 (0.6); 3.3628 (0.4); 3.3318 (112.7); 3.3103 (32.8); 2.6773 (0.5); 2.6727 (0.8); 2.6683 (0.5); 2.5261 (2.4); 2.5126 (46.7); 2.5083 (93.0); 2.5038 (120.1); 2.4992 (86.5); 2.4948 (42.0); 2.3351 (0.5); 2.3307 (0.7); 2.3260 (0.5); 2.1189 (0.4); 2.0872 (1.9); 1.6459 532.7 [M + H].sup.+ (11.6); 1.6285 (11.6); 1.3971 (9.8); 1.2993 (0.4); 1.2593 (0.6); 1.2342 (1.2); 1.1782 (0.3); 1.1414 (1.0); −0.0002 (1.9) I-111 [00301] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 11.3062 (3.6); 9.5815 (2.8); 9.5638 (2.9); 8.9756 (15.5); 8.9634 (16.0); 8.5882 (6.9); 8.4470 (3.0); 8.3944 (10.3); 8.3091 (4.5); 7.6171 (4.1); 7.6049 (7.8); 7.5928 (4.0); 7.0968 (0.6); 7.0909 (1.3); 7.0851 (0.9); 7.0734 (1.1); 7.0676 (2.6); 7.0618 (2.4); 7.0563 (1.0); 7.0434 (4.7); 7.0243 (4.6); 7.0090 (0.7); 6.0364 (0.4); 6.0194 (2.1); 6.0019 (3.3); 5.9843 (2.1); 5.9672 (0.4); 4.1295 (13.7); 3.3335 (81.8); 2.6793 (0.5); 2.6747 (0.7); 2.6702 (0.5); 2.5282 (2.0); 2.5235 (3.3); 2.5147 (43.2); 2.5104 (85.9); 2.5058 (110.2); 2.5013 (78.5); 2.4969 (37.5); 2.3372 (0.5); 2.3326 (0.7); 2.3281 (0.5); 1.6689 (11.4); 1.6515 (11.3); −0.0002 (2.0 ) 557.1 [M + H].sup.+ I-112 [00302] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1529 (2.4); 9.1387 (2.1); 8.8562 (7.4); 8.8475 (5.3); 8.8447 (5.2); 8.3158 (0.6); 8.0284 (4.1); 7.8748 (4.1); 7.7902 (4.3); 7.4427 (2.7); 7.4311 (3.4); 5.9950 (1.7); 5.9812 (2.1); 5.9645 (1.3); 5.7276 (6.7); 3.7913 (0.3); 3.7062 (0.4); 3.6482 (0.8); 3.3259 (321.5); 2.6734 (3.6); 2.5056 (581.4); 2.3323 (3.5); 2.0158 (0.3); 1.8007 (0.4); 1.7882 (0.5); 1.7369 (4.3); 1.6514 (0.4); 1.5846(8.0); 1.5688 (6.6); 1.4241 (0.6); 1.3635 (6.4); 1.2984 (0.5); 1.2273 (16.0); 1.1222 (0.4); 0.8827 (0.3); 0.0112 (18.8); 0.0067 (23.1); 0.0031 (30.7); 0.0005 (34.2) 498.0 [M + H].sup.+ I-113 [00303] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.9592 (1.5); 9.5816 (0.6); 9.5645 (0.7); 8.5796 (1.0); 8.5742 (1.1); 8.4747 (2.2); 8.3255 (1.0); 8.3155 (0.4); 8.1330 (0.6); 8.1273 (0.6); 8.1119 (0.7); 8.1062 (0.7); 7.8591 (1.0); 7.8378 (0.9); 6.1083 (0.4); 6.0912 (0.6); 6.0742 (0.4); 3.6879 (0.7); 3.6366 (0.6); 3.5562 (0.4); 3.3255 (200.3); 2.6754 (0.9); 2.6710 (1.2); 2.5063 (130.7); 2.5019 (168.9); 2.4976 (126.7); 2.3333 (0.8); 2.3288 (1.1); 2.3245 (0.8); 1.6635 (2.1); 1.6461 (2.1); 1.4294 (16.0); 0.1461 (0.5); 0.0077 (5.9); −0.0002 (101.2); −0.0083 (4.5); −0.1495 (0.5) 658.4 [M + H].sup.+ I-114 [00304] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2260 (2.5); 9.2083 (2.5); 8.9278 (4.4); 8.9237 (4.2); 8.9223 (4.2); 8.4439 (3.1); 8.4383 (3.0); 8.4222 (3.2); 8.4166 (3.2); 8.3160 (0.9); 8.0511 (8.5); 8.0470 (16.0); 8.0392 (6.0); 8.0352 (4.8); 8.0308 (2.2); 7.8200 (4.3); 7.8184 (4.4); 7.7983 (4.0); 7.7967 (4.1); 6.0706 (0.5); 6.0533 (1.9); 6.0359 (2.9); 6.0186 (1.9); 5.9863 (6.8); 3.3246 (222.5); 2.8908 (1.3); 2.7308 (1.2); 2.6795 (1.2); 2.6754 (2.4); 2.6709 (3.2); 2.6664 (2.4); 2.5242 (11.8); 2.5107 (199.8); 2.5064 (395.8); 2.5019 (518.0); 2.4974 (376.7); 2.4930 (184.5); 2.3333 (2.2); 2.3287 (3.1); 2.3242 (2.3); 2.0861 (4.6); 2.0745 (0.8); 1.5684 (9.7); 1.5511 (9.6); 1.3977 (0.5); 0.0079 (2.1); −0.0002 (58.1); −0.0086 (2.2) 491.9 [M + H].sup.+ I-115 [00305] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.4969 (3.4); 9.4855 (3.5); 8.5080 (16.0); 8.3178 (4.8); 8.0452 (3.8); 8.0414 (3.7); 8.0312 (4.3); 8.0273 (4.2); 7.7481 (5.4); 7.7342 (5.2); 6.1428 (0.6); 6.1311 (2.5); 6.1195 (3.9); 6.1078 (2.5); 6.0961 (0.6); 5.8624 (0.3); 5.8512 (0.4); 5.8490 (0.5); 5.8418 (0.6); 5.8124 (1.2); 5.7758 (0.5); 3.9265 (0.4); 3.8573 (0.5); 3.7087 (0.3); 3.6812 (0.6); 3.6055 (1.8); 3.5762 (1.6); 3.5686 (1.4); 3.5587 (1.3); 3.5328 (0.9); 3.5304 (0.9); 3.5140 (0.7); 3.5095 (0.6); 3.5038 (0.6); 3.4672 (0.5); 3.4532 (0.6); 3.4493 (0.6); 3.4422 (0.6); 3.4240 (0.7); 3.3896 (4.4); 3.3304 (159.4); 2.6168 (2.0); 2.6137 (2.7); 2.6107 (2.0); 2.5228 (5.5); 2.5197 (6.8); 2.5166 (6.6); 2.5078 (144.4); 2.5048 (319.2); 2.5018 (448.3); 2.4987 (322.7); 2.4957 (148.3); 2.4613 (0.5); 2.3917 (1.0); 2.3888 (2.0); 2.3855 (2.8); 2.3825 (1.9); 2.0729 (0.7); 1.6211 (12.8); 1.6096 (12.8); 1.2811 (0.3); 0.0054 (1.1); −0.0001 (43.8); −0.0057 (1.4) 558.0 [M + H].sup.+ I-116 [00306] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.5519 (4.6); 9.5405 (4.6); 8.5743 (6.8); 8.5706 (6.6); 8.4699 (13.7); 8.3221 (6.2); 8.3132 (1.8); 8.1312 (5.0); 8.1275 (4.4); 8.1172 (5.5); 8.1135 (5.2); 7.8635 (6.0); 7.8495 (5.6); 6.0950 (3.5); 6.0836 (4.8); 6.0720 (3.2); 3.6462 (2.6); 3.3180 (1400.0); 2.6167 (4.2); 2.6136 (6.0); 2.5226 (12.1); 2.5195 (15.1); 2.5164 (15.0); 2.5076 (298.5); 2.5046 (648.8); 2.5016 (900.6); 2.4985 (642.6); 2.4956 (292.3); 2.3854 (6.1); 2.0624 (2.8); 1.6712 (15.9); 1.6595 (16.0); 0.0054 (2.4); −0.0001 (93.0); −0.0057 (3.5) 600.2 [M + H].sup.+ I-117 [00307] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3758 (4.3); 9.3583 (4.4); 8.9300 (7.6); 8.9260 (7.2); 8.9246 (7.0); 8.9087 (0.3); 8.4451 (5.1); 8.4395 (4.9); 8.4234 (5.3); 8.4178 (5.2); 8.3569 (7.8); 8.3156 (0.9); 8.1991 (7.9); 8.1793 (7.5); 8.1447 (0.3); 7.8230 (7.2); 7.8026 (6.7); 7.8012 (7.1); 6.1054 (0.8); 6.0888 (3.1); 6.0715 (4.7); 6.0541 (3.1); 6.0371 (0.8); 5.9872 (12.0); 3.5998 (0.6); 3.3255 (365.2); 2.8912 (1.6); 2.7314 (1.4); 2.6758 (2.1); 2.6713 (2.8); 2.6669 (2.1); 2.5905 (0.4); 2.5068 (321.5); 2.5023 (420.9); 2.4979 (321.7); 2.3336 (1.9); 2.3292 (2.6); 2.3247 (1.9); 2.0864 (6.1); 1.8074 (0.3); 1.7894 (0.4); 1.5925 (16.0); 1.5752 (15.8); 1.4682 (0.3); 1.4506 (1.8); 1.2347 (0.9); 0.8686 (1.3); 0.1459 (1.2); 0.0079 (13.5); −0.0002 (268.7); −0.0083 (13.1): −0.1495 (1.2) 482.0 [M + H].sup.+ I-118 [00308] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.2816 (3.8); 9.2700 (4.2); 9.2581 (0.5); 9.2491 (0.5); 9.2378 (0.4); 8.9223 (6.2); 8.9214 (6.1); 8.9187 (6.1); 8.9025 (0.7); 8.8988 (0.8); 8.4567 (0.4); 8.4530 (0.7); 8.4494 (0.4); 8.4385 (4.8); 8.4348 (4.3); 8.4240 (4.2); 8.4203 (4.1); 8.1051 (0.5); 8.0894 (0.7); 8.0744 (0.5); 8.0166 (4.7); 8.0140 (7.9); 8.0114 (4.5); 7.9906 (0.7); 7.9880 (0.5); 7.9703 (0.8); 7.8168 (6.1); 7.8024 (5.9); 7.7867 (13.2); 7.7678 (0.8); 7.7568 (0.9); 7.7521 (0.9); 7.7373 (0.4); 7.7197 (0.6); 7.2954 (0.3); 7.2537 (0.4); 6.3510 (0.3); 6.0723 (0.8); 6.0610 (2.8); 6.0494 (4.3); 6.0431 (1.0); 6.0378 (2.8); 6.0321 (0.8); 6.0264 (0.7); 6.0209 (0.5); 5.9824 (11.3); 5.8309 (0.4); 4.6634 (0.4); 3.7133 (0.5); 3.7104 (0.3); 3.7044 (0.4); 3.6776 (0.3); 3.6758 (0.4); 3.6671 (0.4); 3.6469 (1.8); 3.4700 (0.3); 3.4621 (0.3); 3.3168 (149.9); 2.6163 (2.3); 2.6133 (3.1); 2.6103 (2.2); 2.5543 (0.5); 2.5517 (0.5); 2.5223 (6.8); 2.5192 (8.4); 2.5161 (8.7); 452.2 [M + H].sup.+ 2.5042 (366.1); 2.5012 (497.7); 2.4983 (370.2); 2.3881 (2.2); 2.3852 (2.9); 2.3822 (2.1); 1.5941 (1.2); 1.5827 (15.6); 1.5711 (16.0); 1.5602 (1.6); 1.2352 (0.6); 0.0053 (2.4); −0.0001 (75.1); −0.0056 (2.4); −0.1002 (0.3) .sup.13C-NMR (150.9 MHz, d.sub.6-DMSO): δ = 163.1414 (4.1); 163.0940 (4.1); 162.2981 (0.6) 159.3685 (3.9); 152.2063 (3.2); 151.9562 (3.7) 148.8020 (2.0); 143.2362 (3.6); 137.3235 (3.2) 134.5441 (3.7); 126.8575 (5.0); 124.5384 (2.8) 120.8941 (0.9); 119.1850 (1.0); 119.1101 (3.7) 116.9726 (2.3); 114.1941 (4.0); 105.7558 (3.7) 72.1199 (0.8); 44.6020 (4.7); 40.2358 (48.0); 40.1162 (254.4); 39.9775 (757.0); 39.8386 (1484.2); 39.6995 (1737.4); 39.5604 (1471.7); 39.4213 (736.5); 39.2822 (239.0); 18.8378 (7.0); 0.2820 (11.2) I-119 [00309] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2437 (3.5); 9.2259 (3.5); 8.8719 (11.2); 8.8600 (11.5); 8.1537 (7.8); 8.1000 (0.4); 8.0634 (3.0); 8.0428 (3.0); 7.9747 (3.0); 7.9522 (3.2); 7.7734 (0.4); 7.4530 (3.1); 7.4410 (5.9); 7.4291 (3.1); 6.2408 (3.1); 6.2285 (3.2); 6.0413 (0.6); 6.0240 (2.4); 6.0068 (3.7); 5.9894 (2.5); 5.9727 (0.7); 5.7553 (1.2); 3.6475 (0.5); 3.5683 (0.4); 3.3248 (60.9); 2.8912 (0.9); 2.7489 (15.7); 2.7367 (16.0); 2.6709 (1.0); 2.5029 (152.7); 2.3290 (1.0); 1.5911 (13.7); 1.5739 (13.7); −0.0002 (1.2) 367.1 [M + H].sup.+ I-120 [00310] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.0715 (1.4); 9.1846 (0.6); 9.1681 (0.6); 9.0050 (0.9); 9.0006 (1.0); 8.5427 (0.7); 8.5371 (0.6); 8.5212 (0.7); 8.5156 (0.7); 7.9496 (1.0); 7.9278 (0.9); 7.5113 (1.3); 7.5076 (1.3); 7.2791 (0.8); 6.0457 (0.4); 6.0284 (0.6); 6.0118 (0.4); 3.3252 (81.1); 2.6754 (0.3); 2.6711 (0.4); 2.6667 (0.3); 2.5108 (28.5); 2.5066 (55.1); 2.5021 (71.0); 2.4976 (51.7); 2.4933 (25.7); 2.3289 (0.4); 2.0352 (0.5); 1.6269 (2.1); 1.6095 (2.1); 1.4363 (16.0); 1.0386 (0.8); 1.0332 (0.9); 1.0227 (0.5); 1.0178 (0.8); 1.0122 (0.8); 0.7969 (0.3); 0.7861 (0.9); 0.7812 (0.9); 0.7739 (0.9); 0.7690 (1.0); −0.0002 (0.3) 356.2 [M + H].sup.+ I-121 [00311] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1953 (3.4); 9.1773 (3.4); 8.9063 (0.6); 8.8984 (0.7); 8.8944 (0.8); 8.8863 (0.7); 8.8687 (15.4); 8.8567 (15.6); 8.3156 (0.8); 7.9775 (4.4); 7.9736 (7.6); 7.9699 (5.0); 7.9475 (0.5); 7.9145 (4.3); 7.9100 (8.0); 7.9056 (4.8); 7.8712 (5.2); 7.8671 (6.9); 7.8631 (4.1); 7.8463 (0.4); 7.4961 (0.4); 7.4839 (0.4); 7.4523 (4.2); 7.4402 (7.8); 7.4282 (4.0); 6.2490 (1.0); 6.2367 (3.2); 6.2242 (3.2); 6.2123 (1.0); 6.0136 (0.6); 5.9966 (2.4); 5.9790 (3.8); 5.9614 (2.4); 5.9442 (0.6); 5.7556 (1.5); 3.3229 (321.3); 2.9028 (1.2); 2.8836 (0.6); 2.7471 (16.0); 2.7345 (16.0); 2.6753 (2.5); 2.6707 (3.3); 2.6664 (2.4); 2.5104 (206.0); 2.5063 (392.4); 438.0 [M + H].sup.+ 2.5018 (502.8); 2.4973 (366.3); 2.4931 (183.4); 2.3329 (2.3); 2.3287 (3.1); 2.3241 (2.3); 1.8290 (1.1); 1.6133 (0.8); 1.5961 (0.9); 1.5726 (13.3); 1.5553 (13.2); 1.4327 (0.6); 1.2350 (0.4); 0.1459 (1.6); 0.0078 (17.9); −0.0002 (355.9); −0.0084 (16.5); −0.1497 (1.6) I-122 [00312] .sup.1H-NMR (400.2 MHz, d6-DMSO): δ = 20.0075 (0.4); 15.9938 (0.4); 9.1085 (3.9); 9.0910 (4.1); 9.0668 (0.4); 9.0548 (0.4); 8.9206 (6.6); 8.9189 (7.2); 8.9151 (7.1); 8.9132 (6.7); 8.7024 (0.7); 8.4411 (5.8); 8.4355 (5.5); 8.4194 (6.0); 8.4138 (6.0); 8.3310 (0.4); 8.3151 (9.5); 7.9508 (0.4); 7.8183 (7.0); 7.8166 (6.9); 7.7967 (6.8); 7.7949 (6.8); 7.5534 (8.6); 7.5497 (5.8); 7.5352 (5.8); 7.5084 (0.5); 7.4758 (0.4); 7.2761 (5.6); 6.0723 (0.7); 6.0572 (3.0); 6.0398 (4.7); 6.0219 (3.1); 6.0035 (0.8); 5.9668 (10.7); 3.9783 (1.2); 3.9157 (0.4); 3.8298 (0.4); 3.8105 (0.4); 3.6991 (0.4); 3.6054 (0.4); 3.5467 (0.4); 3.4749 (0.5); 3.4583 (0.6); 3.3856 (1.1); 3.3740 (1.5); 3.3241 (1617.6); 3.3001 (4.4); 3.2667 (0.4); 3.0884 (0.4); 2.9172 (0.4); 2.8908 (3.0); 2.8689 (0.4); 2.8183 (0.4); 2.7786 (0.5); 2.7460 (0.6); 2.7307 (2.6); 2.6796 (5.5); 2.6752 (11.3); 2.6706 (15.4); 2.6661 (11.4); 2.6616 (5.5); 2.6359 (1.1); 2.5934 (1.7); 2.5241 (56.2); 2.5193 (89.4); 458.1 [M + H].sup.+ 2.5108 (905.2); 2.5063 (1819.6); 2.5017 (2375.8) 2.4971 (1675.2); 2.4925 (783.3); 2.3376 (4.8); 2.3331 (10.4); 2.3285 (14.5); 2.3239 (10.3); 2.3193 (4.6); 2.1173 (0.5); 2.0859 (1.8); 2.0743 (0.7); 2.0624 (1.6); 2.0535 (2.0); 2.0413 (3.5); 2.0291 (2.0); 2.0203 (2.0); 2.0073 (1.0); 1.6912 (0.4); 1.6368 (0.4); 1.5855 (16.0); 1.5681 (15.9); 1.3979 (2.0); 1.3670 (0.4); 1.2478 (0.6); 1.2356 (0.9); 1.2291 (0.9); 1.2107 (0.4); 1.1399 (0.8); 1.0667 (0.4); 1.0531 (1.6); 1.0415 (5.9); 1.0362 (6.2); 1.0253 (2.9); 1.0209 (6.2); 1.0153 (6.3); 1.0045 (2.1); 0.9651 (0.5); 0.8416 (0.4); 0.8018 (2.5); 0.7921 (5.6); 0.7888 (5.7); 0.7797 (5.8); 0.7759 (5.4); 0.7639 (2.3); 0.7206 (0.4); 0.1458 (16.2); 0.1373 (0.7); 0.0897 (0.5); 0.0749 (0.5); 0.0653 (0.5); 0.0617 (0.7); 0.0566 (0.6); 0.0529 (0.8); 0.0492 (0.9); 0.0455 (1.1); 0.0434 (1.2); 0.0426 (1.2); 0.0412 (1.2); 0.0390 (0.9); 0.0382 (1.0); 0.0360 (1.7); 0.0331 (2.6); 0.0316 (2.8); 0.0309 (2.8); 0.0301 (2.8); 0.0294 (2.9); 0.0279 (3.4); 0.0272 (3.7); 0.0265 (3.9); 0.0251 (4.7); 0.0243 (4.3); 0.0220 (7.0); 0.0206 (8.3); 0.0198 (9.1); 0.0176 (12.3); 0.0169 (13.2); 0.0162 (14.1); 0.0079 (158.6); −0.0002 (4100.9); −0.0086 (145.5); −0.0238 (4.8); −0.0398 (1.7); −0.0480 (1.0); −0.0689 (0.5); −0.0799 (0.4); −0.0959 (0.5); −0.1019 (0.4); −0.1041 (0.4); −0.1497 (16.3); −0.1575 (0.7) I-123 [00313] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 10.9231 (3.2); 9.3798 (3.7); 9.3687 (3.8); 9.3203 (0.4); 9.3085 (0.4); 8.6025 (0.4); 8.5973 (6.1); 8.5965 (5.9); 8.5930 (6.2); 8.5922 (5.8); 8.5134 (0.6); 8.5126 (0.6); 8.5091 (0.6); 8.5083 (0.6); 8.2060 (4.6); 8.2016 (4.4); 8.1914 (5.2); 8.1871 (5.4); 8.1483 (6.0); 8.1397 (0.7); 8.1001 (0.6); 8.0915 (5.9); 8.0857 (0.9); 8.0812 (0.6); 8.0701 (5.7); 7.8237 (6.6); 7.8231 (6.3); 7.8092 (6.4); 7.8084 (6.0); 7.6987 (0.7); 7.6841 (0.6); 7.6833 (0.6); 6.5158(0.4); 6.4913 (0.6); 6.4743 (0.5); 6.2977 (4.2); 6.2948 (4.0); 6.2693 (3.2); 6.2663 (3.1); 5.9891 (0.5); 5.9850 (0.6); 5.9735 (2.7); 5.9621 (4.1); 5.9507 (2.7); 5.9391 (0.6); 5.7950 (4.4); 5.7920 (3.7); 5.7780 (3.3); 5.7750 (3.9); 4.1052 (1.2); 4.0965 (3.7); 4.0877 (3.8); 4.0789 (1.3); 3.3363 (0.3); 3.3227 (118.7); 3.1746 (16.0); 3.1659 (15.7); 2.6182 (0.5); 2.6151 (0.7); 2.6121 (0.5); 2.5241 (1.6); 2.5211 (1.8); 2.5179 499.1 [M + H].sup.+ (1.8); 2.5092 (35.2); 2.5061 (75.3); 2.5031 (105.6); 2.5000 (78.0); 2.4970 (36.1); 2.3900 (0.4); 2.3870 (0.6); 2.3840 (0.4); 1.6477 (13.9); 1.6361 (14.0); 1.6248 (0.6); 1.6132 (0.4); 1.5829 (1.5); 1.5714 (1.5) .sup.13C-NMR (150.9 MHz, d.sub.6-DMSO): δ = 163.2528 (3.4); 163.1075 (0.4); 162.9138 (0.4); 162.4435 (0.5); 157.8891 (3.0); 157.7948 (0.5); 155.4866 (2.7); 148.8173 (3.4); 146.7468 (4.5); 146.3373 (0.5); 139.7420 (4.9); 139.3769 (0.5); 136.7866 (0.4); 136.5526 (3.9); 134.5459 (4.0); 131.5733 (3.1); 131.2155 (1.4); 130.9970 (1.4); 130.9185 (1-6); 130.7783 (0.5); 129.8412 (3.2); 128.3004 (2.6); 128.2539 (1.6); 125.9299 (0.6); 124.1203 (1.2); 122.9941 (1.8); 122.9692 (1.7); 122.3103 (1.2); 120.5007 (0.4); 117.7137 (4.8); 116.2207 (0.6); 48.7687 (3.4); 44.0829 (0.6); 44.0107 (4.8); 40.2360 (11.0); 40.1162 (57.8); 39.9775 (172.6); 39.8386 (338.8); 39.6995 (397.0); 39.5604 (336.4); 39.4213 (168.4); 39.2822 (54.7); 18.9961 (0.7); 18.7947 (7.0) I-124 [00314] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 10.7177 (1.9); 9.1690 (4.2); 9.1526 (4.3); 9.0193 (0.3); 9.0064 (6.7); 9.0047 (7.2); 9.0009 (7.3); 8.9992 (6.9); 8.5503 (5.7); 8.5447 (5.4); 8.5287 (6.0); 8.5231 (6.0); 8.3157 (0.6); 7.9627 (6.4); 7.9614 (6.6); 7.9413 (6.0); 7.9398 (6.2); 7.5144 (9.1); 7.5107 (8.3); 7.5054 (6.0); 7.5025 (6.2); 7.2754 (6.1); 6.0581 (0.7); 6.0411 (3.2); 6.0241 (4.6); 6.0071 (3.0); 5.9898 (0.6); 5.9690 (0.4); 5.8168 (0.4); 3.3244 (155.9); 2.6761 (1.2); 2.6715 (1.7); 2.6669 (1.2); 2.6624 (0.6); 2.5249 (5.2); 2.5201 (8.6); 2.5115 (97.6); 2.5071 (198.3); 2.5025 (260.8); 2.4980 (187.8); 2.4935 (90.7); 2.3385 (0.6); 2.3339 (1.2); 2.3294 (1.7); 2.3248 (1.2); 2.3204 (0.6); 2.0745 (6.1); 2.0680 (6.6); 2.0557 (4.9); 2.0472 (3.6); 2.0345 (4.5); 2.0258 (2.0); 2.0220 (2.6); 2.0136 (2.3); 2.0009 (1.2); 1.6395 (16.0); 1.6221 (15.9); 1.5866 (0.7); 1.5693 (0.6); 1.3469 (1.6); 1.0513 (2.2); 1.0400 (6.2); 1.0345 (6.8); 1.0307 (3.6); 1.0240(3.5); 1.0191 500.1 [M + H].sup.+ (6.4); 1.0136 (6.4); 1.0032 (2.6); 0.7917 (2.8); 0.7809 (7.2); 0.7758 (7.2); 0.7686 (6.6); 0.7635 (7.6); 0.7520 (2.2); 0.1459 (1.5); 0.0080 (14.0); −0.0001 (361.3); −0.0085 (13.8); −0.1496 (1.5) I-126 [00315] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.5983 (3.5); 9.5871 (3.6); 8.5480 (11.2); 8.3454 (4.9); 8.0016 (15.8); 6.6601 (1.0); 6.6521 (3.2); 6.6437 (3.2); 6.6354 (1.0); 6.0209 (0.5); 6.0094 (2.4); 5.9979 (3.7); 5.9864 (2.4); 5.9748 (0.5); 3.6635 (6.1); 3.6531 (12.0); 3.6486 (11.6); 3.3193 (29.4); 2.7404 (15.9); 2.7321 (16.0); 2.6179 (0.4); 2.6151 (0.6); 2.6120 (0.4); 2.5240 (1.1); 2.5209 (1.3); 2.5178 (1.3); 2.5089 (27.2); 2.5060 (57.7); 2.5029 (80.0); 2.4999 (58.7); 2.4970 (27.6); 2.3899 (0.4); 2.3868 (0.5); 2.3838 (0.4); 2.0757 (3.1); 1.6223 (12.5); 1.6106 (12.5); 0.0053 (0.4); −0.0001 (12.5); −0.0057 (0.4) .sup.13C-NMR (150.9 MHz, d.sub.6-DMSO): δ = 164.1849 (4.3); 163.2775 (3.2); 160.2210 (3.6); 159.8269 (3.5); 158.4937 (4.1); 141.9436 (3.6); 135.9002 (3.7); 131.0035 (0.8); 130.7826 (2.6); 130.5621 (2.6); 130.3417 (0.8); 129.1643 (4.1); 128.5089 (2.7); 125.9904 (0.8); 125.3732 (1.0); 578.1 [M + H].sup.+ 124.1812 (2.2); 122.3721 (2.2); 120.5633 (0.5); 66.1823 (6.1); 43.8331 (4.4); 40.2357 (9.7); 40.1163 (52.1); 39.9775 (155.2); 39.8386 (304.3); 39.6995 (356.3); 39.5604 (301.7); 39.4213 (151.0); 39.2822 (49.0); 29.3257 (6.4); 18.4308 (7.0); 1.3248 (0.6); 0.2743 (2.3) I-127 [00316] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.5032 (3.1); 9.4913 (3.2); 8.8732 (15.1); 8.8652 (15.5); 8.4706 (10.8); 8.3118 (4.7); 7.4492 (4.0); 7.4411 (7.6); 7.4331 (4.0); 6.2383 (0.9); 6.2300 (3.0); 6.2216 (3.0); 6.2132 (0.9); 6.0749 (0.5); 6.0634 (2.3); 6.0517 (3.6); 6.0400 (2.3); 6.0284 (0.5); 3.3204 (37.7); 2.7501 (15.9); 2.7417 (16.0); 2.6184 (0.3); 2.6154 (0.4); 2.6124 (0.3); 2.5244 (1.0); 2.5213 (1.2); 2.5183 (1.2); 2.5093 (24.8); 2.5064 (52.1); 2.5034 (71.7); 2.5004 (53.6); 2.4975 (25.8); 2.3873 (0.4); 2.0762 (0.4); 1.6178 (12.6); 1.6063 (12.6); −0.0001 (1.3) 460.1 [M + H].sup.+ I-128 [00317] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2456 (3.0); 9.2278 (3.1); 8.8722 (15.6); 8.8601 (16.0); 8.3160 (0.3); 8.1539 (7.7); 8.1508 (4.9); 8.0707 (1.9); 8.0675 (2.2); 8.0644 (2.4); 8.0614 (2.1); 8.0498 (2.0); 8.0466 (2.3); 8.0436 (2.3); 8.0405 (2.0); 7.9796 (2.0); 7.9761 (2.3); 7.9736 (2.2); 7.9700 (1.8); 7.9559 (2.2); 7.9523 (2.5); 7.9499 (2.2); 7.9462 (1.8); 7.4537 (4.2); 7.4416 (7.9); 7.4295 (4.1); 6.2554 (0.9); 6.2432 (2.9); 6.2306 (2.9); 6.2183 (0.9); 6.0408 (0.5); 6.0235 (2.3); 6.0060 (3.6); 5.9885 (2.3); 5.9711 (0.5); 3.3283 (156.2); 2.7484 (15.6); 2.7358 (15.6); 2.6763 (0.8); 2.6716 (1.1); 2.6673 (0.8); 2.5250 (3.4); 2.5114 (66.6); 2.5072 (132.0); 2.5027 (170.7); 2.4982 (124.0); 2.4939 (61.7); 2.3339 (0.8); 2.3295 (1.1); 2.3251 (0.8); 2.0750 (0.9); 1.5908 (12.9); 1.5735 367.1 [M + H].sup.+ (12.8); −0.0002 (3.0) I-129 [00318] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2669 (2.8); 9.2491 (2.9); 8.8683 (15.6); 8.8562 (16.0); 8.3162 (0.5); 7.9719 (4.0); 7.9679 (6.2); 7.9640 (4.2); 7.7700 (4.1); 7.7496 (4.3); 7.7471 (4.3); 7.4503 (4.2); 7.4382 (7.7); 7.4261 (4.0); 6.2498 (0.8); 6.2376 (2.7); 6.2249 (2.7); 6.2126 (0.8); 6.0278 (0.4); 6.0104 (2.1); 5.9929 (3.4); 5.9753 (2.1); 5.9581 (0.4); 3.3259 (157.0); 2.7486 (14.9); 2.7360 (14.9); 2.6804 (0.6); 2.6760 (1.2); 2.6715 (1.6); 2.6669 (1.1); 2.5250 (4.9); 2.5201 (7.8); 2.5115 (93.6); 2.5071 (186.6); 2.5025 (240.4); 2.4980 (171.2); 2.4935 (82.2); 2.3339 (1.1); 2.3293 (1.5); 2.3248 (1.1); 2.3203 (0.5); 1.5877 (11.8); 1.5704 (11.8); −0.0002 (4.9) 442.1 [M + H].sup.+ I-130 [00319] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2697 (2.9); 9.2518 (2.9); 8.8697 (15.6); 8.8576 (16.0); 8.1056 (4.2); 8.1019 (6.7); 8.0982 (4.2); 7.8751 (4.3); 7.7780 (4.1); 7.7754 (4.4); 7.7730 (3.8); 7.4515 (4.2); 7.4394 (7.7); 7.4273 (4.1); 6.2514 (0.8); 6.2391 (2.7); 6.2265 (2.8); 6.2141 (0.8); 6.0274 (0.4); 6.0103 (2.2); 5.9928 (3.4); 5.9752 (2.2); 5.9579 (0.4); 3.3286 (57.8); 2.7504 (15.2); 2.7378 (15.0); 2.6773 (0.4); 2.6729 (0.6); 2.6684 (0.4); 2.5263 (1.8); 2.5128 (35.3); 2.5084 (69.6); 2.5039 (88.9); 2.4993 (63.2); 2.4949 (30.2); 2.3351 (0.4); 2.3307 (0.5); 2.3260 (0.4); 1.5874 (12.0); 1.5701 (11.9): −0.0002 (1.8) 486.0 [M + H].sup.+ I-131 [00320] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1973 (2.7); 9.1795 (2.7); 8.8696 (12.7); 8.8575 (13.0); 8.0237 (2.5); 8.0197 (5.5); 8.0156 (5.4); 8.0044 (16.0); 8.0002 (10.1); 7.4531 (3.4); 7.4411 (6.3); 7.4290 (3.3); 6.2510 (0.7); 6.2393 (2.1); 6.2265 (2.1); 6.2151 (0.7); 6.0124 (0.4); 5.9953 (1.9); 5.9777 (3.0); 5.9600 (2.0); 5.9425 (0.4); 3.3280 (74.1); 2.7481 (11.5); 2.7358 (11.4); 2.6764 (0.6); 2.6719 (0.8); 2.6675 (0.6); 2.5252 (2.5); 2.5074 (100.2); 2.5029 (127.0); 2.4985 (91.7); 2.3341 (0.6); 2.3298 (0.8); 2.3253 (0.6); 1.5717 (10.9); 1.5543 (10.8); 1.0562 (0.6); −0.0002 (2.4) 481.9 [M + H].sup.+ I-132 [00321] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0872 (3.3); 9.0692 (3.4); 8.8668 (14.4); 8.8548 (14.6); 7.4982 (11.1); 7.4955 (10.8); 7.4477 (4.1); 7.4357 (7.2); 7.4236 (3.7); 7.2669 (5.2); 6.2293 (1.0); 6.2169 (3.0); 6.2043 (3.0); 6.1922 (1.0); 6.0184 (0.5); 6.0014 (2.3); 5.9838 (3.6); 5.9662 (2.4); 5.9489 (0.5); 3.3300 (66.2); 3.0182 (0.5); 3.0061 (0.5); 2.7499 (16.0); 2.7373 (15.9); 2.6729 (0.6); 2.6684 (0.4); 2.5081 (69.7); 2.5038 (87.9); 2.4995 (64.5); 2.3305 (0.5); 2.3260 (0.4); 2.0626 (0.7); 2.0501 (1.4); 2.0417 (1.6); 2.0293 (2.8); 2.0169 (1.7); 2.0085 (1.5); 1.9958 (0.8); 1.5879 (13.1); 1.5706 (13.1); 1.0460 (1.6); 1.0348 (4.9); 1.0293 (5.2); 1.0185 (2.8); 1.0139 (4.9); 1.0085 (4.8); 0.9981 (1.9); 0.8575 (0.5); 0.8398 (0.6); 448.1 [M + H].sup.+ 0.7930 (2.1); 0.7821 (5.8); 0.7774 (5.7); 0.7701 (5.3); 0.7651 (5.9); 0.7535 (1.6); −0.0002 (1.4) I-133 [00322] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6187 (0.5); 9.6013 (0.6); 8.9933 (2.8); 8.9812 (2.8); 8.4542 (1.9); 8.3265 (0.8); 7.6313 (0.7); 7.6191 (1.4); 7.6070 (0.7); 6.0630 (0.4); 6.0456 (0.6); 6.0280 (0.4); 5.7595 (0.4); 3.3327 (18.0); 3.2136 (7.1); 2.5258 (0.5); 2.5210 (0.8); 2.5124 (11.8); 2.5080 (23.8); 2.5034 (31.2); 2.4988 (22.4); 2.4943 (10.7); 1.6749 (2.1); 1.6575 (2.1); 1.3208 (16.0); −0.0002 (5.6) 560.0 [M + H].sup.+ I-134 [00323] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.4998 (0.7); 9.4880 (0.7); 8.8731 (0.3); 8.8620 (1.1); 8.8543 (1.1); 8.4770 (2.7); 8.3123 (1.2); 7.4361 (0.5); 6.3516 (0.3); 6.0516 (0.4); 6.0401 (0.5); 6.0285 (0.4); 3.6473 (0.5); 3.5683 (16.0); 2.5238 (0.7); 2.5208 (0.9); 2.5177 (0.9); 2.5087 (19.3); 2.5058 (39.8); 2.5028 (54.6); 2.4999 (40.8); 1.6155 (2.4); 1.6040 (2.3); −0.0001 (6.7) 446.1 [M + H].sup.+ I-135 [00324] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.9105 (1.3); 9.5857 (0.6); 9.5684 (0.6); 8.9599 (2.9); 8.9478 (3.0); 8.4393 (2.0); 8.3110 (0.9); 7.5892 (0.8); 7.5771 (1.4); 7.5650 (0.8); 6.0305 (0.4); 6.0132 (0.6); 5.9958 (0.4); 3.3263 (15.8); 2.5259 (0.4); 2.5125 (7.8); 2.5082 (15.6); 2.5036 (20.4); 2.4991 (14.7); 2.4947 (7.2); 1.6635 (2.1); 1.6461 (2.1); 1.4239 (16.0); 0.0079 (1.2); −0.0002 (29.0); −0.0086 (1.2) 546.2 [M + H].sup.+ I-136 [00325] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3509 (3.1); 9.3330 (3.2); 8.8720 (15.5); 8.8599 (15.9); 8.3101 (5.9); 8.1598 (7.8); 7.4528 (4.2); 7.4407 (7.8); 7.4286 (4.0); 6.2514 (0.9); 6.2391 (3.0); 6.2265 (3.0); 6.2143 (0.9); 6.0486 (0.5); 6.0314 (2.3); 6.0138 (3.6); 5.9962 (2.3); 5.9792 (0.5); 3.3279 (91.3); 2.7498 (16.0); 2.7372 (15.8); 2.6766 (0.7); 2.6722 (1.0); 2.6679 (0.7); 2.5256 (2.9); 2.5120 (59.8); 2.5078 (115.9); 2.5033 (147.3); 2.4988 (106.7); 2.4947 (52.9); 2.3346 (0.7); 2.3301 (0.9); 2.3257 (0.7); 1.5954 (12.8); 1.5780 (12.8); −0.0001 (3.0) 472.0 [M + H].sup.+ I-137 [00326] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1854 (0.9); 9.1675 (0.9); 8.8726 (3.9); 8.8605 (4.0); 7.8782 (2.9); 7.8750 (2.8); 7.7311 (1.2); 7.7267 (1.9); 7.7222 (1.0); 7.4527 (1.0); 7.4406 (2.0); 7.4286 (1.0); 6.2288 (0.8); 6.2161 (0.8); 6.0182 (0.6); 6.0006 (0.9); 5.9829 (0.6); 3.3294 (34.2); 2.7504 (4.1); 2.7379 (4.1); 2.5249 (0.7); 2.5114 (14.5); 2.5073 (27.6); 2.5029 (34.9); 2.4984 (25.0); 2.4942 (12.2); 1.7071 (16.0); 1.5967 (3.4); 1.5793 (3.3) 425.1 [M + H].sup.+ I-138 [00327] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1191 (0.7); 9.1008 (0.8); 8.8842 (3.5); 8.8721 (3.6); 7.4780 (1.1); 7.4658 (4.2); 7.4539 (1.0); 7.2665 (1.1); 5.9945 (0.5); 5.9769 (0.8); 5.9592 (0.5); 5.7561 (1.6); 3.3249 (15.9); 2.9437 (16.0); 2.5248 (0.7); 2.5115 (12.3); 2.5072 (23.8); 2.5028 (30.7); 2.4983 (22.2); 2.4940 (11.0); 2.0403 (0.4); 2.0280 (0.6); 2.0156 (0.4); 2.0072 (0.4); 1.6055 (3.0); 1.5881 (3.0); 1.0440 (0.4); 1.0335 (1.0); 1.0278 (1.1); 1.0181 (0.6); 1.0127 (1.0); 1.0070 (1.0); 0.9973 (0.4); 0.7899 (0.5); 0.7795 (1.1); 0.7763 (1.1); 0.7675 (1.1); 0.7634 (1.0); 0.7518 (0.4); 0.0076 (2.0); −0.0002 (40.6); −0.0084 (1.8) 462.2 [M + H].sup.+ I-139 [00328] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3021 (0.7); 9.2841 (0.7); 8.8878 (3.8); 8.8757 (3.9); 8.0810 (1.0); 8.0772 (1.6); 8.0734 (1.0); 7.8721 (1.0); 7.7557 (0.9); 7.7531 (1.0); 7.7506 (0.9); 7.4825 (1.0); 7.4704 (1.9); 7.4583 (1.0); 6.0067 (0.5); 5.9892 (0.8); 5.9715 (0.5); 3.3276 (16.1); 2.9458 (16.0); 2.5261 (0.4); 2.5128 (8.0); 2.5084 (15.6); 2.5039 (19.9); 2.4993 (13.9); 2.4948 (6.5); 1.6076 (2.9); 1.5903 (2.9); 0.0077 (1.3); −0.0002 (27.2); −0.0087 (0.9) 502.0 [M + H].sup.+ I-140 [00329] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2332 (0.7); 9.2153 (0.7); 8.8879 (3.5); 8.8758 (3.6); 8.0206 (0.8); 8.0163 (1.6); 8.0120 (1.2); 7.9872 (4.1); 7.9829 (3.2); 7.4846 (0.9); 7.4725 (1.8); 7.4604 (0.9); 5.9912 (0.5); 5.9736 (0.8); 5.9560 (0.6); 5.7564 (3.9); 3.3249 (11.4); 2.9448 (16.0); 2.5251 (0.6); 2.5118 (11.7); 2.5075 (22.7); 2.5030 (29.2); 2.4985 (21.1); 2.4942 (10.4); 1.5942 (3.0); 1.5768 (3.0); 0.0079 (0.8); −0.0002 (19.0); −0.0084 (0.7) 496.0 [M + H].sup.+ I-141 [00330] .sup.1H-NMR (600.1 MHz, CD3CN): δ = 8.7959 (2.5); 8.7878 (2.5); 8.3201 (1.9); 8.1432 (0.8); 7.3240 (0.7); 7.3160 (1.4); 7.3079 (0.7); 6.1539 (0.5); 6.1416 (0.6); 6.1298 (0.5); 2.9874 (16.0); 2.1525 (12.4); 1.9490 (2.3); 1.9449 (4.5); 1.9408 (6.6); 1.9366 (4.5); 1.9325 (2.3); 1.6454 (3.4); 1.6339 (3.4); −0.0001 (0.4) 474.1 [M + H].sup.+ I-142 [00331] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3102 (3.2); 9.2928 (3.3); 8.9274 (5.4); 8.9257 (5.8); 8.9219 (5.8); 8.9201 (5.5); 8.4469 (4.6); 8.4412 (4.4); 8.4252 (4.8); 8.4195 (4.9); 8.1485 (4.6); 8.1447 (7.5); 8.1409 (4.6); 7.9123 (5.8); 7.9106 (5.8); 7.8905 (9.4); 7.8888 (10.1); 7.8108 (4.4); 7.8082 (4.9); 7.8057 (4.2); 6.4890 (0.9); 6.4769 (3.0); 6.4643 (3.0); 6.4517 (0.9); 6.0904 (0.5); 6.0734 (2.4); 6.0560 (3.8); 6.0387 (2.4); 6.0212 (0.5); 3.3280 (71.4); 2.7675 (16.0); 2.7550 (15.9); 2.6773 (0.6); 2.6727 (0.9); 2.6681 (0.7); 2.5262 (2.9); 2.5214 (4.4); 2.5128 (52.9); 2.5083 (108.5); 2.5037 (141.7); 2.4991 (99.7); 2.4946 (46.7); 2.3352 (0.6); 2.3305 (0.8); 2.3260 (0.6); 1.5883 (12.8); 1.5709 (12.7); 1.2337 (0.4); 0.1459 (0.8); 0.0080 (6.6); −0.0002 (191.3); −0.0085 (6.8); 510.0 [M + H].sup.+ −0.1496 (0.8) I-143 [00332] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2428 (2.4); 9.2254 (2.6); 8.9306 (4.3); 8.9252 (4.4); 8.4465 (2.8); 8.4409 (2.7); 8.4248 (2.9); 8.4192 (3.0); 8.0455 (7.2); 8.0419 (16.0); 8.0371 (7.0); 8.0043 (0.4); 7.9096 (4.4); 7.8879 (4.1); 6.4893 (0.7); 6.4771 (2.3); 6.4646 (2.3); 6.4524 (0.7); 6.0776 (0.4); 6.0603 (1.8); 6.0430 (2.8); 6.0256 (1.8); 6.0083 (0.4); 3.3273 (55.2); 2.9149 (0.4); 2.7658 (11.5); 2.7533 (11.5); 2.6768 (0.5); 2.6722 (0.6); 2.6677 (0.5); 2.5255 (1.9); 2.5118 (39.7); 2.5077 (80.2); 2.5033 (105.1); 2.4988 (76.3); 2.4946 (37.9); 2.3344 (0.5); 2.3300 (0.6); 2.3256 (0.5); 1.5731 (9.6); 1.5557 (9.6); 0.1457 (0.5); 0.0079 (3.6); −0.0002 (103.1); −0.0084 (4.5); −0.1497 (0.5) 506.0 [M + H].sup.+ I-144 [00333] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2240 (2.9); 9.2061 (3.0); 8.9003 (14.1); 8.8882 (14.4); 8.0202 (3.1); 8.0160 (6.8); 8.0117 (4.6); 7.9822 (16.0); 7.9779 (12.8); 7.5104 (3.8); 7.4983 (7.2); 7.4862 (3.7); 6.0101 (0.4); 5.9930 (2.1); 5.9755 (3.3); 5.9579 (2.1); 5.9406 (0.4); 4.3628 (0.4); 4.3501 (0.7); 4.3373 (0.4); 3.6982 (6.2); 3.6869 (8.9); 3.6745 (7.0); 3.4565 (0.6); 3.4438 (0.6); 3.4390 (0.6); 3.4263 (0.6); 3.3485 (7.3); 3.3272 (77.8); 2.6768 (0.5); 2.6723 (0.7); 2.6678 (0.5); 2.5257 (2.3); 2.5123 (44.0); 2.5079 (85.7); 2.5034 (109.3); 2.4989 (77.5); 2.4945 (37.2); 2.3348 (0.5); 2.3302 (0.7); 2.3258 (0.5); 1.5959 (11.5); 1.5785 (11.4); 1.0740 (1.2); 1.0566 (2.3); 1.0391 (1.1); 0.0077 (0.5); −0.0002 (12.8); −0.0086 (0.4) 538.0 [M + H].sup.+ I-145 [00334] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.5204 (3.4); 9.5085 (3.5); 8.9028 (15.6); 8.8947 (16.0); 8.4403 (11.5); 8.3084 (4.9); 7.5043 (4.2); 7.4962 (8.0); 7.4881 (4.1); 6.0724 (0.5); 6.0608 (2.4); 6.0491 (3.9); 6.0374 (2.5); 6.0258 (0.5); 3.6925 (7.7); 3.6847 (10.6); 3.6765 (8.4); 3.3499 (8.3); 3.3417 (9.8); 3.3338 (7.4); 3.3208 (17.8); 2.6163 (0.4); 2.5253 (0.8); 2.5223 (1.0); 2.5192 (1.0); 2.5102 (21.3); 2.5073 (45.2); 2.5043 (62.6); 2.5013 (46.5); 2.4984 (22.2); 2.3882 (0.4); 1.6408 (13.3); 1.6292 (13.4); 0.0053 (0.4); −0.0001 (12.6); −0.0057 (0.4) 516.2 [M + H].sup.+ I-146 [00335] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1104 (3.3); 9.0925 (3.3); 8.8963 (15.6); 8.8842 (16.0); 7.5030 (4.2); 7.4909 (7.9); 7.4788 (4.2); 7.4639 (11.3); 7.4603 (11.4); 7.2638 (4.9); 6.0140 (0.5); 5.9968 (2.3); 5.9792 (3.7); 5.9615 (2.4); 5.9443 (0.5); 3.6970 (7.2); 3.6859 (10.6); 3.6734 (8.2); 3.3496 (8.6); 3.3295 (88.3); 2.6773 (0.4); 2.6729 (0.6); 2.6683 (0.4); 2.5261 (2.0); 2.5126 (38.5); 2.5084 (75.0); 2.5039 (95.8); 2.4994 (69.4); 2.4951 (34.6); 2.3351 (0.4); 2.3307 (0.6); 2.3263 (0.4); 2.0591 (0.6); 2.0465 (1.4); 2.0381 (1.5); 2.0257 (2.8); 2.0132 (1.7); 2.0048 (1.5); 1.9921 (0.8); 1.6084 (12.9); 1.5910 (12.9); 1.0434 (1.6); 1.0330 (4.2); 1.0274 (4.6); 1.0176 (2.7); 1.0122 (4.4); 1.0065 (4.4); 0.9968 (1.9); 0.7859 (2.0); 0.7757 (4.6); 0.7723 (4.8); 0.7634 (4.7); 0.7595 (4.5); 0.7479 (1.6); 0.0080 (0.4); −0.0001 (9.7); −0.0083 (0.4) 504.2 [M + H].sup.+ I-147 [00336] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2904 (3.3); 9.2727 (3.3); 8.8987 (15.7); 8.8866 (16.0); 8.0744 (4.4); 8.0708 (7.3); 8.0672 (4.6); 7.8706 (4.8); 7.7475 (4.9); 7.5068 (4.2); 7.4947 (7.9); 7.4826 (4.0); 6.0244 (0.5); 6.0074 (2.3); 5.9899 (3.7); 5.9724 (2.4); 5.9552 (0.5); 3.6976 (7.4); 3.6865 (10.5); 3.6741 (8.1); 3.3501 (8.6); 3.3371 (12.3); 3.3274 (93.5); 2.6771 (0.6); 2.6726 (0.8); 2.6682 (0.6); 2.5256 (3.2); 2.5121 (54.7); 2.5080 (104.0); 2.5036 (131.4); 2.4991 (94.0); 2.4947 (45.7); 2.3349 (0.6); 2.3304 (0.8); 2.3259 (0.6); 1.6087 (12.9); 1.5913 (12.8); 0.0078 (0.6); −0.0002 (15.4); −0.0084 (0.6) 544.0 [M + H].sup.+ I-148 [00337] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4192 (4.0); 9.4017 (4.2); 9.0134 (0.4); 9.0013 (0.3); 8.9398 (7.0); 8.9381 (7.5); 8.9343 (7.5); 8.9325 (7.0); 8.4475 (6.1); 8.4419 (5.7); 8.4258 (6.3); 8.4201 (6.3); 8.3517 (5.8); 8.3479 (10.9); 8.3441 (6.3); 8.3153 (0.8); 8.2560 (6.0); 8.2515 (8.9); 8.2474 (6.0); 8.1540 (6.5); 8.1496 (9.8); 8.1451 (5.6); 7.8287 (7.4); 7.8271 (7.3); 7.8070 (7.1); 7.8053 (7.1); 6.3370 (0.3); 6.1225 (0.6); 6.1053 (3.0); 6.0880 (4.8); 6.0706 (3.1); 6.0529 (0.6); 5.9934 (11.2); 3.3711 (0.9); 3.3315 (62.2); 3.3256 (304.5); 2.7072 (0.7); 2.6948 (0.7); 2.6803 (0.9); 2.6758 (1.9); 2.6712 (2.6); 2.6667 (1.9); 2.6624 (0.8); 2.5248 (8.2); 2.5200 (12.3); 2.5113 (159.1); 2.5069 (326.9); 2.5023 (426.6); 2.4977 (298.3); 2.4932 (137.9); 2.3382 (0.9); 2.3337 (1.9); 446.1 [M + H].sup.+ 2.3291 (2.6); 2.3245 (1.8); 2.3200 (0.8); 1.5994 (16.0); 1.5821 (15.9); 0.1459 (3.5); 0.0079 (30.6); −0.0002 (837.5); −0.0086 (28.6); −0.1496 (3.5) I-149 [00338] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.8482 (0.7); 9.6000 (1.3); 9.5822 (1.4); 9.2338 (0.8); 8.9941 (1.6); 8.9459 (6.1); 8.9338 (6.2); 8.7482 (0.6); 8.7377 (0.6); 8.5275 (0.6); 8.5244 (0.7); 8.5064 (0.8); 8.4598 (0.4); 8.4308 (5.6); 8.3096 (2.2); 7.9544 (1.4); 7.5696 (1.6); 7.5575 (3.1); 7.5454 (1.6); 7.5162 (0.6); 7.5052 (0.6); 7.4950 (0.6); 7.4842 (0.5); 6.9299 (0.4); 6.9109 (0.3); 6.0546 (0.9); 6.0370 (1.4); 6.0194 (0.9); 4.0568 (0.5); 4.0390 (1.5); 4.0213 (1.5); 4.0035 (0.5); 3.7338 (15.0); 3.6526 (0.5); 3.6364 (1.2); 3.6198 (1.6); 3.6035 (1.2); 3.5868 (0.5); 3.3319 (25.3); 3.1696 (0.6); 3.1511 (1.8); 3.1328 (1.9); 3.1144 (0.8); 3.0938 (13.3); 2.9506 (7.6); 2.8929 (9.2); 2.7338 (8.1); 2.6913 (16.0); 2.6783 (0.4); 490.1 [M + H].sup.+ 2.6735 (0.5); 2.5798 (0.5); 2.5533 (0.4); 2.5088 (63.5); 2.5045 (79.2); 2.5001 (56.8); 2.3313 (0.5); 2.3269 (0.4); 1.9900 (6.6); 1.9107 (3.9); 1.8726 (0.6); 1.6652 (5.2); 1.6478 (5.2); 1.5295 (0.7); 1.4036 (1.3); 1.3807 (11.8); 1.3423 (0.6); 1.3217 (4.2); 1.2982 (0.9); 1.2659 (15.2); 1.2497 (14.8); 1.2439 (11.1); 1.2249 (3.3); 1.2119 (0.8); 1.1941 (2.2); 1.1763 (3.5); 1.1585 (1.8); 1.0876 (0.3); 1.0816 (0.3); 0.1460 (0.3); 0.0076 (3.4); −0.0002 (75.7); −0.0083 (3.8); −0.1495 (0.4) I-150 [00339] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2929 (1.2); 9.2750 (1.2); 8.9399 (7.0); 8.9278 (7.2); 8.0215 (1.5); 8.0171 (3.1); 8.0128 (2.0); 7.9678 (7.5); 7.9634 (6.4); 7.5709 (1.8); 7.5588 (3.5); 7.5467 (1.8); 5.9773 (0.9); 5.9598 (1.4); 5.9421 (0.9); 5.7556 (3.7); 3.7368 (16.0); 3.3259 (58.2); 3.0901 (13.6); 2.6763 (0.4); 2.6718 (0.5); 2.6672 (0.4); 2.5252 (1.7); 2.5205 (2.5); 2.5118 (30.6); 2.5074 (62.6); 2.5028 (81.9); 2.4982 (57.5); 2.4937 (26.8); 2.3341 (0.4); 2.3296 (0.5); 2.3251 (0.4); 1.6173 (5.0); 1.5998 (5.0); 0.1458 (0.4); 0.0080 (3.6); −0.0002 (99.4); −0.0086 (3.3); −0.1496 (0.4) 511.9 [M + H].sup.+ I-151 [00340] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3623 (1.1); 9.3445 (1.1); 8.9394 (6.8); 8.9272 (7.0); 8.0601 (1.6); 8.0563 (2.8); 8.0526 (1.8); 7.8731 (1.7); 7.7394 (1.5); 7.7368 (1.7); 7.7341 (1.5); 7.5680 (1.8); 7.5558 (3.3); 7.5437 (1.7); 5.9929 (0.9); 5.9753 (1.4); 5.9577 (0.9); 3.7357 (16.0); 3.3271 (34.9); 3.0913 (13.5); 2.6724 (0.3); 2.5259 (1.0); 2.5211 (1.6); 2.5125 (21.7); 2.5080 (44.7); 2.5035 (58.8); 2.4989 (41.6); 2.4943 (19.7); 2.3302 (0.4); 1.6307 (4.9); 1.6132 (4.9); 0.0079 (2.6); −0.0002 (74.0); −0.0086 (2.6) 516.0 [M + H].sup.+ I-152 [00341] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1882 (1.4); 9.1702 (1.5); 8.9384 (6.5); 8.9263 (6.5); 7.5650 (1.8); 7.5529 (3.3); 7.5408 (1.7); 7.4530 (5.0); 7.4496 (5.0); 7.2688 (2.2); 5.9829 (1.0); 5.9653 (1.6); 5.9477 (1.0); 5.7574 (1.7); 3.7356 (16.0); 3.3304 (17.6); 3.0914 (14.1); 2.5092 (23.6); 2.5049 (28.9); 2.5005 (20.4); 2.0460 (0.6); 2.0375 (0.7); 2.0252 (1.2); 2.0127 (0.7); 2.0043 (0.6); 1.6326 (5.6); 1.6152 (5.6); 1.3970 (0.5); 1.0434 (0.7); 1.0330 (1.9); 1.0275 (2.0); 1.0176(1.3); 1.0121 (1.9); 1.0066(1.8); 0.9970 (0.8); 0.7864 (0.9); 0.7762 (2.1); 0.7732 (2.2); 0.7641 (2.1); 0.7605 (1.9); 0.7488 (0.7); −0.0002 (27.7); −0.0085 (1.1) 478.1 [M + H].sup.+ I-153 [00342] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6387 (1.2); 9.6207 (1.2); 8.9485 (6.9); 8.9363 (7.0); 8.5945 (2.3); 8.4557 (2.1); 8.3870 (2.0); 8.3162 (0.5); 7.5731 (1.8); 7.5610 (3.4); 7.5489 (1.7); 6.0650 (0.9); 6.0474 (1.4); 6.0296 (0.9); 3.7347 (16.0); 3.3687 (13.9); 3.3256 (179.6); 3.0944 (13.6); 2.6801 (0.6); 2.6756 (1.2); 2.6710 (1.7); 2.6665 (1.2); 2.6618 (0.6); 2.5245 (5.7); 2.5197 (8.6); 2.5111 (103.2); 2.5066 (211.3); 2.5021 (276.8); 2.4975 (194.4); 2.4930 (90.6); 2.3379 (0.6); 2.3334 (1.2); 2.3288 (1.7); 2.3243 (1.2); 2.3199 (0.6); 1.6677 (4.9); 1.6503 (4.9); 0.1458 (2.5); 0.0260 (0.5); 0.0217 (0.6); 0.0078 (21.5); −0.0002 (564.1); −0.0087 (19.7); −0.0205 (0.8); −0.0286 (0.4); −0.0316 (0.4); −0.1497 (2.6) 500.1 [M + H].sup.+ I-154 [00343] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1108 (4.0); 9.0933 (4.2); 8.9217 (7.0); 8.9199 (7.5); 8.9161 (7.5); 8.9143 (7.2); 8.4420 (6.1); 8.4364 (5.8); 8.4203 (6.4); 8.4147 (6.4); 8.3162 (0.5); 7.8197 (7.3); 7.8180 (7.4); 7.7981 (7.0); 7.7963 (7.2); 7.5552 (8.9); 7.5516 (6.1); 7.5396 (5.2); 7.5370 (5.8); 7.5345 (5.1); 7.2768 (5.7); 6.0760 (0.7); 6.0590 (3.0); 6.0415 (4.8); 6.0241 (3.1); 6.0064 (0.7); 5.9695 (9.8); 5.7558 (1.0); 3.3256 (81.7); 2.6807 (0.5); 2.6762 (1.2); 2.6716 (1.6); 2.6671 (1.2); 2.6626 (0.5); 2.5251 (5.0); 2.5204 (7.3); 2.5117 (96.6); 2.5072 (200.5); 2.5027 (263.0); 2.4981 (183.7); 2.4935 (84.9); 2.3387 (0.5); 2.3341 (1.1); 2.3295 (1.6); 2.3249 (1.1); 2.3204 (0.5); 2.0753 (0.8); 2.0627 (1.8); 2.0544 (1.9); 2.0506 (1.4); 2.0420 (3.6); 2.0333 (1.3); 2.0294 (2.0); 2.0211 (1.9); 2.0084 (1.0); 1.5869 (16.0); 1.5695 (15.9); 1.0536 (1.6); 1.0424(6.0); 1.0368 (6.5); 1.0262(2.6); 1.0215 (6.2); 1.0159 (6.2); 1.0056 (1.9); 0.8032 (2.6); 0.7931 458.3 [M + H].sup.+ (5.6); 0.7900 (5.6); 0.7872 (5.5); 0.7807 (5.8); 0.7768 (5.5); 0.7650 (2.1); 0.1459 (2.2); 0.0249 (0.4); 0.0207 (0.6); 0.0079 (19.0); −0.0001 (532.3); −0.0086 (17.8); −0.0281 (0.4); −0.1496 (2.3) I-155 [00344] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2125 (0.9); 9.1950 (0.9); 8.9321 (1.5); 8.9305 (1.6); 8.9266 (1.6); 8.9249 (1.5); 8.4443 (1.2); 8.4387 (1.2); 8.4226 (1.3); 8.4170 (1.4); 7.9366 (0.9); 7.9328 (2.1); 7.9280 (3.0); 7.9232 (2.2); 7.9196 (0.9); 7.8245 (1.6); 7.8229 (1.6); 7.8029 (1.5); 7.8012 (1.6); 7.7468 (1.3); 7.7422 (2.3); 7.7376 (1.2); 6.0769 (0.6); 6.0595 (1.0); 6.0421 (0.7); 5.9789 (2.4); 5.7553 (6.9); 3.3254 (41.2); 2.6713 (0.4); 2.5249 (1.3); 2.5202 (1.8); 2.5115 (26.8); 2.5070 (55.7); 2.5024 (73.3); 2.4978 (51.3); 2.4933 (23.9); 2.3292 (0.4); 1.7268 (0.9); 1.7164 (16.0); 1.5957 (3.4); 1.5783 (3.4); 0.1458 (0.6); 0.0132 (0.5); 0.0078 (5.0); −0.0002 (151.0); −0.0087 (5.3); −0.0178 (0.4); −0.1498 (0.6) 435.2 [M + H].sup.+ I-156 [00345] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2645 (0.8); 9.2469 (0.8); 8.9484 (1.4); 8.9439 (1.4); 8.9429 (1.3); 8.4654 (1.0); 8.4598 (1.0); 8.4438 (1.1); 8.4381 (1.1); 7.9344 (1.4); 7.9127 (1.4); 7.9058 (0.8); 7.9020 (1.7); 7.8976 (1.6); 7.8945 (1.4); 7.8902 (1.8); 7.8866 (0.8); 7.7486 (1.1); 7.7440 (2.0); 7.7395 (1.0); 6.0987 (0.6); 6.0812 (0.9); 6.0638 (0.6); 3.3281 (14.8); 2.9666 (16.0); 2.5262 (0.5); 2.5213 (0.8); 2.5128 (9.4); 2.5084 (19.3); 2.5039 (25.2); 2.4994 (17.8); 2.4950 (8.4); 1.7148 (14.4); 1.6132 (3.1); 1.5958 (3.0); 0.0077 (1.7); −0.0002 (43.2); −0.0086 (1.5 ) 463.1 [M + H].sup.+ I-157 [00346] .sup.1H-NMR (400.2 MHz, d6-DMSO): δ = 9.4694 (0.7); 9.4518 (0.8); 8.9557 (1.2); 8.9541 (1.3); 8.9502 (1.4); 8.9485 (1.3); 8.4690 (1.1); 8.4634 (1.0); 8.4473 (1.1); 8.4417 (1.1); 8.3260 (1.0); 8.3222 (2.0); 8.3184 (1.2); 8.2355 (1.1); 8.2310 (1.6); 8.2269 (1.1); 8.1547 (1.2); 8.1503 (1.8); 8.1458 (1.0); 7.9388 (1.4); 7.9372 (1.3); 7.9171 (1.3); 7.9155 (1.2); 6.1270 (0.6); 6.1095 (0.9); 6.0919 (0.6); 3.3279 (20.2); 2.9680 (16.0); 2.8923 (0.4); 2.7334 (0.4); 2.5263 (0.4); 2.5216 (0.6); 2.5128 (9.1); 2.5084 (18.9); 2.5038 (24.7); 2.4992 (17.3); 2.4947 (8.0); 1.6193 (3.0); 1.6019 (2.9); 1.2600 (0.4); 1.2446 (0.4); 0.0079 (1.7); −0.0002 (46.7); −0.0086 (1.5) 474.1 [M + H].sup.+ I-158 [00347] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5703 (3.2); 9.5528 (3.4); 8.9685 (5.7); 8.9669 (6.2); 8.9630 (6.2); 8.9613 (6.0); 8.4893 (11.4); 8.4842 (16.0); 8.4681 (5.4); 8.4625 (5.4); 8.3211 (5.1); 7.9432 (6.3); 7.9415 (6.2); 7.9216 (6.0); 7.9198 (6.0); 6.1633 (0.5); 6.1460 (2.5); 6.1286 (4.0); 6.1112 (2.6); 6.0940 (0.5); 3.6940 (6.8); 3.6829 (9.6); 3.6703 (7.7); 3.3769 (8.1); 3.3646 (9.7); 3.3530 (8.0); 3.3386 (126.8); 2.6794 (0.5); 2.6749 (0.7); 2.6703 (0.5); 2.5284 (2.0); 2.5237 (3.0); 2.5150 (40.7); 2.5105 (84.8); 2.5059 (111.0); 2.5013 (77.1); 2.4967 (35.2); 2.3373 (0.5); 2.3328 (0.6); 2.3281 (0.5); 2.0773 (0.7); 1.6407 (13.5); 1.6233 (13.4); 0.1459 (0.4); 0.0080 (3.0); −0.0002 (96.2); −0.0086 (2.9); −0.1496 (0.4) 540.1 [M + H].sup.+ I-159 [00348] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2532 (0.8); 9.2359 (0.8); 8.9649 (1.4); 8.9611 (1.4); 8.9595 (1.4); 8.4871 (1.1); 8.4815 (1.1); 8.4655 (1.2); 8.4599 (1.2); 7.9377 (1.4); 7.9362 (1.4); 7.9162 (1.3); 7.9145 (1.4); 7.8933 (1.9); 7.8891 (3.0); 7.8851 (2.1); 7.7472 (1.1); 7.7426 (2.0); 7.7380 (1.0); 6.0947 (0.6); 6.0773 (1.0); 6.0598 (0.6); 3.6928 (1.6); 3.6814 (2.3); 3.6689 (1.8); 3.3770 (1.9); 3.3648 (2.3); 3.3535 (1.7); 3.3295 (87.6); 2.6762 (0.3); 2.6716 (0.5); 2.6672 (0.3); 2.5251 (1.4); 2.5204 (2.1); 2.5116 (28.8); 2.5072 (59.4); 2.5026 (77.9); 2.4980 (54.7); 2.4935 (25.4); 2.3340 (0.4); 2.3293 (0.5); 2.3249 (0.4); 2.0746 (16.0); 1.7112 (15.4); 1.6133 (3.1); 1.5959 (3.1); 0.0080 (2.3); −0.0002 (65.7); −0.0086 (1.9) 505.1 [M + H].sup.+ I-160 [00349] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4593 (4.2); 9.4419 (4.3); 8.9730 (7.4); 8.9712 (7.8); 8.9675 (7.9); 8.9657 (7.4); 8.4910 (6.4); 8.4854 (6.0); 8.4693 (6.7); 8.4637 (6.8); 8.3215 (6.1); 8.3177 (11.5); 8.3138 (6.7); 8.2312 (6.2); 8.2266 (9.2); 8.2226 (6.3); 8.1545 (7.0); 8.1501 (10.2); 8.1456 (5.8); 7.9508 (0.6); 7.9425 (7.6); 7.9408 (7.5); 7.9209 (7.2); 7.9191 (7.2); 6.1416 (0.6); 6.1243 (3.0); 6.1069 (4.9); 6.0895 (3.1); 6.0721 (0.6); 3.6951 (8.4); 3.6841 (11.9); 3.6715 (9.4); 3.6428 (0.3); 3.3778 (10.0); 3.3660 (11.7); 3.3548 (8.7); 3.3268 (178.1); 3.1483 (0.4); 2.8916 (3.3); 2.7328 (2.7); 2.7317 (2.7); 2.6902 (1.2); 2.6811 (0.5); 2.6764 (1.1); 2.6718 (1.5); 2.6672 (1.1); 2.6627 (0.5); 2.6106 (0.4); 2.5254 (4.5); 2.5207 (6.7); 2.5120 (91.5); 2.5075 (188.6); 2.5029 (247.2); 2.4983 (172.3); 2.4937 (79.3); 2.3388 (0.5); 2.3343 (1.1); 2.3297 (1.5); 2.3252 (1.1); 2.3209 (0.5); 1.6200 (16.0); 1.6026 (15.8); 1.2737 (1.9); 1.2590 (3.1); 1.2435 (3.1); 1.2253 (0.6); 0.1460 (1.0); 0.0080 (8.8); 516.1 [M + H].sup.+ −0.0001 (266.6); −0.0085 (8.3); −0.1496 (1.0) I-161 [00350] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1583 (4.1); 9.1408 (4.2); 8.9562 (7.1); 8.9546 (7.4); 8.9507 (7.5); 8.9491 (7.0); 8.4836 (5.7); 8.4780 (5.4); 8.4620 (6.1); 8.4564 (6.1); 7.9326 (7.4); 7.9311 (7.2); 7.9110 (7.0); 7.9094 (6.9); 7.5167 (8.8); 7.5131 (6.5); 7.5048 (5.3); 7.5021 (5.9); 7.2760 (5.8); 6.0914 (0.6); 6.0743 (2.9); 6.0569 (4.7); 6.0394 (3.0); 6.0220 (0.6); 3.6948 (8.3); 3.6837 (11.9); 3.6711 (9.3); 3.3734 (10.0); 3.3608 (12.9); 3.3421 (164.2); 2.6787 (0.5); 2.6741 (0.7); 2.6695 (0.5); 2.5276 (2.1); 2.5229 (3.2); 2.5142 (44.0); 2.5097 (90.8); 2.5052 (118.4); 2.5006 (82.5); 2.4960 (38.0); 2.3365 (0.5); 2.3319 (0.7); 2.3274 (0.5); 2.0762 (0.9); 2.0731 (0.8); 2.0604 (1.8); 2.0520 (1.9); 2.0483 (1.3); 2.0395 (3.6); 2.0308 (1.3); 2.0270 (2.0); 2.0187 (1.9); 2.0061 (0.9); 1.6076 (16.0); 1.5902 (15.8); 1.0531 (2.2); 1.0419 (5.9); 1.0363 (6.4); 1.0325 (3.2); 1.0258 (3.3); 1.0210 (6.1); 1.0154 (6.1); 1.0051 (2.5); 0.7982 (2.6); 0.7874 (6.8); 0.7823 (6.7); 0.7752 (6.3); 0.7700 (7.3); 0.7585 (2.1); 528.1 [M + H].sup.+ 0.0080 (1.0); −0.0002 (34.0); −0.0085 (1.0) I-162 [00351] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5790 (0.7); 9.5615 (0.7); 8.9508 (1.3); 8.9468 (1.3); 8.9453 (1.2); 8.4876 (2.6); 8.4690 (1.0); 8.4634 (1.0); 8.4474 (1.0); 8.4417 (1.0); 8.3204 (1.2); 7.9397 (1.3); 7.9382 (1.3); 7.9181 (1.2); 7.9165 (1.2); 6.1462 (0.5); 6.1288 (0.9); 6.1112 (0.6); 3.3287 (17.1); 2.9651 (16.0); 2.5268 (0.6); 2.5133 (12.6); 2.5090 (25.2); 2.5045 (32.6); 2.5000 (23.0); 2.4955 (10.9); 1.6368 (3.0); 1.6194 (3.0); 0.0078 (2.4); −0.0002 (63.2); −0.0086 (2.4) .sup.13C-NMR (150.9 MHz, d.sub.6-DMSO): δ = 164.7515 (2.0); 163.3696 (1.6); 159.6955 (2.1); 152.2614 (1.7); 151.9645 (2.1); 143.3199 (2.0); 136.1945 (1.8): 130.9554 (0.4); 130.7351 (1.2); 130.5146 (1.3); 130.2942 (0.4); 128.4651 (1.4); 125.9801 (0.4); 125.2412 (0.6); 124.1708 (1.0); 498.1 [M + H].sup.+ 122.3621 (0.9); 120.5526 (0.2); 116.9099 (1.2); 114.6690 (2.3); 106.0916 (1.9); 44.5403 (2.4); 40.2357 (3.8); 40.1162 (19.9); 39.9775 (59.2); 39.8386 (116.0); 39.6995 (135.8); 39.5604 (115.1); 39.4213 (57.6); 39.2822 (18.7); 37.8999 (7.0); 18.7989 (3.5); 0.2703 (0.3 I-163 [00352] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO); δ = 9.2809 (0.8); 9.2631 (0.8); 8.9431 (4.3): 8.9310 (4.4); 7.8362 (2.2); 7.8328 (2.8); 7.8294 (2.3); 7.7314 (1.2); 7.7268 (2.0); 7.7223 (1.0); 7.5696 (1.1); 7.5575 (2.2); 7.5454 (1.1); 6.0011 (0.6); 5.9835 (1.0); 5.9658 (0.6); 5.7561 (1.9); 3.7368 (10.2); 3.3271 (25.0); 3.0928 (8.8); 2.8915 (1.8); 2.7321 (1.5); 2.5253 (0.9); 2.5119 (13.8); 2.5076 (28.0); 2.5031 (36.8); 2.4986 (26.4); 2.4941 (12.7); 1.7018 (16.0); 1.6404 (3.3); 1.6230 (3.3); 1.3973 (0.4); 0.0078 (1.5); −0.0002 (38.8); −0.0086 (1.4) 455.1 [M + H].sup.+ I-164 [00353] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1676 (0.7); 9.1499 (0.7); 8.9409 (1.1); 8.9394 (1.2); 8.9354 (1.2); 8.9338 (1.2); 8.4636 (1.0); 8.4579 (0.9); 8.4419 (1.0); 8.4363 (1.0); 7.9295 (1.2); 7.9279 (1.3); 7.9078 (1.2); 7.9061 (1.2); 7.5180 (1.5); 7.5143 (1.2); 7.5069 (0.9); 7.5042 (1.0); 7.2790 (1.0); 6.0744 (0.5); 6.0569 (0.8); 6.0393 (0.5); 3.3289 (21.9); 2.9622 (16.0); 2.5259 (0.7); 2.5212 (1.0); 2.5125 (12.4); 2.5080 (25.3); 2.5035 (32.9); 2.4988 (23.0); 2.4943 (10.6); 2.0421 (0.6); 2.0296 (0.3); 2.0212 (0.3); 1.6032(2.9); 1.5858 (2.8); 1.0533 (0.4); 1.0421 (1.0); 1.0365 (1.1); 1.0327 (0.6); 1.0261 (0.6); 1.0212 (1.0); 1.0156 (1.0); 1.0053 (0.4); 0.8024 (0.4); 0.7917 (1.2); 0.7865 (1.2); 0.7794 (1.1); 0.7742 (1.2); 0.7628 (0.4): 0.0079 (2.3); −0.0002 (62.8); −0.0086 (2.0) 486.1 [M + H].sup.+ I-165 [00354] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5528 (0.7); 9.5350 (0.7); 9.0032 (7.3); 8.4653 (2.6); 8.3150 (1.2); 6.0304 (0.6); 6.0128 (0.9); 5.9952 (0.6); 3.3296 (15.2); 2.9489 (16.0); 2.5276 (0.4); 2.5228 (0.7); 2.5142 (8.6); 2.5098 (17.6); 2.5053 (23.1); 2.5007 (16.4); 2.4963 (7.8); 1.6340 (3.0); 1.6166 (3.0); 0.0078 (0.9); −0.0002 (24.7); −0.0086 (0.8) 508.0 [M + H].sup.+ I-166 [00355] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1352 (0.7); 9.1173 (0.7); 8.9915 (8.2); 7.4836 (2.1); 7.4802 (2.1); 7.2737 (1.0); 5.9570 (0.5); 5.9394 (0.8); 5.9217 (0.5); 3.3264 (27.4); 2.9444 (16.0); 2.5253 (0.8); 2.5206 (1.2); 2.5119 (15.8); 2.5074 (33.1); 2.5029 (43.7); 2.4982 (31.0); 2.4937 (14.6); 2.0346 (0.6); 2.0220 (0.3); 2.0137 (0.3); 1.5985 (2.8); 1.5811 (2.8); 1.0485 (0.4); 1.0377 (1.0); 1.0320 (1.0); 1.0279 (0.6); 1.0218 (0.6); 1.0168 (1.0); 1.0111 (1.0); 1.0009 (0.4); 0.7959 (0.4); 0.7854 (1.1); 0.7801 (1.1); 0.7730 (1.0); 0.7680 (1.2); 0.7567 (0.4); 0.0079 (1.8); −0.0002 (53.3); −0.0086 (1.8) 496.0 [M + H].sup.+ I-167 [00356] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6396 (1.4); 9.6234 (1.5); 8.6392 (7.7); 8.6107 (1.7); 8.4726 (2.3); 8.4690 (3.4); 8.4654 (1.9); 8.1531 (2.3); 8.1049 (2.4); 6.0480 (1.0); 6.0310 (1.4); 6.0140 (1.0); 5.9981 (0.4); 5.7560 (0.5); 4.3291 (0.8); 4.3114 (0.8); 3.3638 (17.1); 3.3545 (1.0); 3.3259 (57.9); 2.6717 (1.1); 2.6671 (0.6); 2.6012 (16.0); 2.5250 (2.2); 2.5202 (3.3); 2.5115 (46.3); 2.5071 (95.5); 2.5026 (125.5); 2.4981 (89.0); 2.4937 (42.2); 2.3338 (0.6); 2.3294 (0.8); 2.3249 (0.6); 1.6412 (5.2); 1.6237 (5.3); 1.6130 (1.4); 1.3618 (0.9); 1.3442 (1.9); 1.3265 (0.9); 1.2073 (0.4); 1.1906 (0.4); 0.1460 (0.5); 0.0079 (3.9); −0.0002 (119.0); −0.0086 (3.9); −0.1496 (0.5) 533.1 [M + H].sup.+ I-168 [00357] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5512 (3.0); 9.5338 (3.1); 8.9383 (5.2); 8.9369 (5.7); 8.9329 (5.6); 8.9312 (5.4); 8.5110 (10.8); 8.4510 (5.0); 8.4454 (5.2); 8.4294 (4.8); 8.4237 (4.8); 8.4068 (0.3); 8.3231 (4.8); 7.9201 (5.7); 7.9184 (5.7); 7.8984 (5.3); 7.8966 (5.4); 6.4879 (0.8); 6.4757 (2.8); 6.4632 (2.9); 6.4507 (0.8); 6.1528 (0.5); 6.1355 (2.4); 6.1182 (3.8); 6.1008 (2.4); 6.0836 (0.5); 3.3301 (29.6); 2.7701 (16.0); 2.7576 (15.8); 2.6786 (0.5); 2.6741 (0.6); 2.6696 (0.4); 2.5276 (2.0); 2.5229 (3.1); 2.5142 (37.8); 2.5097 (77.9); 2.5052 (101.8); 2.5006 (71.4); 2.4960 (33.1); 2.3366 (0.4); 2.3320 (0.6); 2.3274 (0.4); 1.6230 (12.6); 1.6056 (12.5); 0.1459 (0.5); 0.0079 (4.4); −0.0002 (127.9); −0.0086 (4.2); −0.1496 (0.5) 484.1 [M + H].sup.+ I-169 [00358] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3775 (2.7); 9.3595 (2.8); 8.8636 (15.6); 8.8515 (16.0); 8.3153 (1.2); 8.3096 (4.0); 8.3059 (7.4); 8.3021 (4.3); 8.2102 (3.9); 8.2056 (6.2); 8.2016 (4.1); 8.1376 (4.5); 8.1331 (6.8); 8.1287 (3.8); 7.4492 (4.1); 7.4371 (7.7); 7.4250 (4.1); 6.0548 (0.4); 6.0370 (2.0); 6.0196 (3.2); 6.0019 (2.0); 5.9849 (0.4); 5.7455 (8.1); 3.3709 (0.4); 3.3251 (247.6); 2.6800 (0.8); 2.6756 (1.6); 2.6710 (2.3); 2.6665 (1.7); 2.6620 (0.8); 2.5245 (7.0); 2.5198 (10.8); 2.5111 (141.8); 2.5067 (293.2); 2.5021 (385.3); 2.4975 (269.2); 2.4930 (124.6); 2.3377 (0.8); 2.3335 (1.6); 2.3289 (2.3); 2.3244 (1.6); 1.5987 (11.1); 1.5814 (11.0); 0.1458 (1.8); 0.0079 422.1 [M + H].sup.+ (14.7); −0.0002 (430.2); −0.0086 (13.4); −0.0202 (0.5); −0.1496 (1.8) I-170 [00359] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2333 (0.7); 9.2154 (0.7); 8.9977 (8.7); 7.8679 (3.2); 7.8634 (3.5); 7.7396 (1.1); 7.7350 (1.9); 7.7304 (1.0); 5.9800 (0.6); 5.9625 (0.8); 5.9448 (0.5); 5.7556 (7.3); 3.3268 (25.8); 2.9484 (16.0); 2.5254 (0.7); 2.5207 (1.2); 2.5120 (13.4); 2.5076 (27.0); 2.5031 (35.1); 2.4985 (24.7); 2.4940 (11.6); 1.7093 (14.6); 1.6087 (2.9); 1.5913 (2.9); 0.0080 (1.5); −0.0002 (38.5); −0.0085 (1.3) 473.1 [M + H].sup.+ I-171 [00360] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4394 (0.8); 9.4214 (0.8); 9.0030 (7.5); 8.2954 (1.0); 8.2919 (1.9); 8.2882 (1.2); 8.2084 (1.0); 8.2042 (1.7); 8.2002 (1.1); 8.1445 (1.1); 8.1403 (1.8); 8.1360 (1.0); 6.0074 (0.6); 5.9899 (0.9); 5.9723 (0.6); 5.7556 (0.7); 3.3256 (28.6); 3.3205 (9.9); 2.9494 (16.0); 2.5249 (0.9); 2.5114 (17.7); 2.5072 (34.9); 2.5028 (45.0); 2.4984 (32.4); 1.6152 (3.1); 1.5978 (3.1); 0.0077 (2.1); −0.0002 (49.1); −0.0084 (2.0) 484.0 [M + H].sup.+ I-172 [00361] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3759 (4.1); 9.3585 (4.2); 8.9315 (7.0); 8.9298 (7.2); 8.9260 (7.4); 8.9242 (6.7); 8.4450 (6.0); 8.4394 (5.7); 8.4233 (6.3); 8.4177 (6.3); 8.3574 (7.3); 8.3152 (0.6); 8.1995 (7.1); 8.1787 (6.7); 7.8250 (7.4); 7.8233 (7.2); 7.8033 (7.1); 7.8016 (7.0); 6.1065 (0.6); 6.0895 (3.0); 6.0722 (4.8); 6.0548 (3.1); 6.0376 (0.7); 5.9871 (11.2); 5.7554 (2.7); 3.3262 (258.4); 2.8728 (0.6); 2.6809 (0.6); 2.6764 (1.1); 2.6718 (1.5); 2.6672 (1.1); 2.6627 (0.5); 2.5253 (4.9); 2.5205 (7.6); 2.5119 (88.8); 2.5074 (178.8); 2.5029 (234.4); 2.4982 (167.9); 2.4937 (79.4); 2.3387 (0.5); 2.3343 (1.1); 2.3297 (1.5); 2.3251 (1.0); 2.3205 (0.5); 1.5932 (16.0); 1.5759 (15.9); 0.1460 (0.6); 0.0080 (5.0); −0.0002 (147.0); −0.0085 (4.8); −0.1495 (0.6) 480.0 [M + H].sup.+ I-173 [00362] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5350 (4.1); 9.5176 (4.2); 8.9346 (6.9); 8.9330 (7.3); 8.9291 (7.4); 8.9273 (6.9); 8.5166 (14.0); 8.4468 (6.0); 8.4412 (5.7); 8.4251 (6.3); 8.4195 (6.3); 8.3237 (6.2); 7.8292 (7.3); 7.8276 (7.4); 7.8076 (6.9); 7.8058 (7.0); 6.1438 (0.6); 6.1270 (3.0); 6.1096 (4.8); 6.0922 (3.1); 6.0751 (0.6); 5.9900 (11.4); 3.3259 (281.4); 2.8905 (0.6); 2.6808 (0.6); 2.6763 (1.4); 2.6718 (1.9); 2.6672 (1.4); 2.6627 (0.6); 2.5253 (5.4); 2.5206 (8.0); 2.5119 (111.4); 2.5074 (228.4); 2.5028 (300.4); 2.4982 (212.8); 2.4937 (99.8); 2.3387 (0.6); 2.3342 (1.4); 2.3297 (1.9); 2.3251 (1.3); 2.3206 (0.6); 1.6177 (16.0); 1.6004 (16.0); 0.0080 (2.3); −0.0002 (74.3); −0.0085 (2.2) 470.1 [M + H].sup.+ I-174 [00363] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1540 (4.1); 9.1365 (4.2); 8.9558 (6.8); 8.9541 (7.4); 8.9503 (7.3); 8.9485 (7.1); 8.4838 (6.2); 8.4782 (5.8); 8.4621 (6.5); 8.4565 (6.6); 8.3157 (0.4); 7.9324 (7.4); 7.9307 (7.4); 7.9108 (7.0); 7.9090 (7.2); 7.5159 (8.9); 7.5122 (6.4); 7.5036 (5.1); 7.5009 (5.7); 7.4983 (5.0); 7.2750 (5.5); 6.0903 (0.6); 6.0733 (3.0); 6.0558 (4.9); 6.0384 (3.1); 6.0210 (0.6); 3.6939 (8.1); 3.6827 (11.5); 3.6701 (9.1); 3.3729 (9.4); 3.3607 (11.1); 3.3491 (8.0); 3.3270 (144.4); 2.6769 (0.7); 2.6723 (0.9); 2.6677 (0.7); 2.5258 (2.5); 2.5211 (3.8); 2.5124 (51.5); 2.5079 (106.3); 2.5033 (140.8); 2.4987 (100.6); 2.4941 (47.2); 2.3348 (0.6); 2.3302 (0.9); 2.3256 (0.6); 2.0725 (0.8); 2.0599 (1.8); 2.0514 (1.8); 2.0477 (1.3); 2.0390 (3.6); 2.0304 (1.2); 2.0265 (2.0); 2.0182 (1.9); 2.0056 (0.9); 1.6063 (16.0); 1.5889 (15.9); 1.0521 (2.3); 1.0410 (5.9); 1.0354 (6.3); 1.0314 (3.3); 1.0249 (3.2); 1.0200 (6.1); 1.0144 (6.0); 1.0041 (2.5); 0.7975 (2.6); 0.7868 (6.7); 0.7816 (6.8); 528.3 [M + H].sup.+ 0.7745 (6.2); 0.7693 (7.3); 0.7578 (2.1); 0.0080 (1.7); −0.0002 (55.3); −0.0085 (1.6) I-175 [00364] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5671 (1.4); 9.5497 (1.5); 8.9681 (2.5); 8.9663 (2.6); 8.9625 (2.6); 8.9607 (2.4); 8.4891 (4.5); 8.4837 (6.8); 8.4677 (2.4); 8.4620 (2.4); 8.3204 (2.1); 7.9428 (2.7); 7.9411 (2.6); 7.9212 (2.6); 7.9194 (2.5); 6.1456 (1.1); 6.1282 (1.7); 6.1108 (1.1); 3.6936 (2.8); 3.6826 (4.0); 3.6699 (3.2); 3.3768 (3.3); 3.3645 (3.9); 3.3530 (2.7); 3.3274 (34.9); 2.5272 (0.7); 2.5224 (1.1); 2.5138 (15.3); 2.5093 (31.2); 2.5047 (41.0); 2.5001 (29.1); 2.4955 (13.5); 2.0766 (16.0); 1.6401 (5.6); 1.6227 (5.6); 0.0080 (0.6); −0.0002 (17.7); −0.0086 (0.5) 540.3 [M + H].sup.+ I-176 [00365] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5501 (0.6); 9.5323 (0.6); 9.0015 (9.0); 8.4624 (2.2); 8.3157 (1.1); 6.0276 (0.5); 6.0100 (0.8); 5.9924 (0.5); 3.3295 (62.2); 2.9473 (16.0); 2.5260 (0.6); 2.5214 (0.9); 2.5126 (14.0); 2.5081 (29.2); 2.5035 (38.8); 2.4988 (27.6); 2.4943 (12.9); 1.6319 (2.8); 1.6145 (2.8); −0.0002 (1.1) 508.1 [M + H].sup.+ I-177 [00366] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1361 (0.7); 9.1181 (0.7); 8.9917 (9.5); 7.4850 (2.2); 7.4816 (2.1); 7.2739 (1.0); 5.9587 (0.5); 5.9410 (0.8); 5.9234 (0.5); 3.3304 (26.4); 2.9454 (16.0); 2.5219 (0.4); 2.5132 (6.1); 2.5087 (12.7); 2.5041 (16.8); 2.4994 (12.0); 2.4949 (5.6); 2.0474 (0.3); 2.0350 (0.6); 2.0224 (0.4); 2.0141 (0.3); 1.5998 (2.9); 1.5824 (2.9); 1.0490 (0.4); 1.0381 (1.0); 1.0325 (1.1); 1.0283(0.6); 1.0222 (0.6); 1.0172(1.0); 1.0115 (1.0); 1.0014 (0.4); 0.7965 (0.5); 0.7860 (1.1); 0.7807 (1.1); 0.7736 (1.1); 0.7685 (1.2); 0.7573 (0.4); −0.0002 (0.5) 496.2 [M + H].sup.+ I-178 [00367] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2336 (0.7); 9.2157 (0.8); 8.9980 (9.0); 7.8686 (3.3); 7.8640 (3.6); 7.7402 (1.2); 7.7355 (2.0); 7.7309 (1.0); 5.9807 (0.5); 5.9632 (0.9); 5.9456 (0.6); 3.3281 (20.5); 2.9489 (16.0); 2.5212 (0.5); 2.5127 (6.9); 2.5083 (14.0); 2.5037 (18.2); 2.4991 (12.9); 2.4946 (6.0); 2.0758 (1.6); 1.7099 (14.5); 1.6094 (3.0); 1.5920 (2.9); −0.0002 (0.5) 473.2 [M + H].sup.+ I-179 [00368] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4394 (0.7); 9.4215 (0.7); 9.0029 (9.7); 8.2963 (1.0); 8.2924 (2.0); 8.2886 (1.1); 8.2091 (1.0); 8.2045 (1.6); 8.2004(1.1); 8.1452 (1.2); 8.1408 (1.7); 8.1362 (1.0); 6.0079 (0.5); 5.9904 (0.9); 5.9728 (0.6); 3.3296 (31.2); 3.3212 (8.8); 2.9499 (16.0); 2.5213 (0.5); 2.5127 (6.9); 2.5081 (14.2); 2.5035 (18.7); 2.4989 (13.2); 2.4944 (6.1); 1.6159 (2.9); 1.5986 (2.9); −0.0002 (0.6) 484.1 [M + H].sup.+ I-180 [00369] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4844 (2.4); 9.4666 (2.4); 8.8728 (12.8); 8.8607 (13.1); 8.4777 (0.4); 8.4741 (0.6); 8.4705 (0.3); 8.3836 (3.4); 8.3801 (6.1); 8.3765 (3.5); 8.2031 (0.3); 8.1322 (3.5); 8.1300 (3.2); 8.0204 (3.6); 7.9517 (0.3); 7.4523 (3.5); 7.4402 (6.6); 7.4281 (3.4); 6.2559 (0.7); 6.2437 (2.2); 6.2309 (2.2); 6.2185 (0.7); 6.0729 (0.4); 6.0559 (1.8); 6.0384 (2.8); 6.0208 (1.8); 6.0033 (0.4); 5.7584 (8.2); 3.4742 (1.8); 3.4558 (6.3); 3.4374 (6.5); 3.4237 (1.1); 3.4191 (2.0); 3.3294 (173.7); 2.8865 (10.6); 2.7516 (12.5); 2.7390 (12.4); 2.6806 (0.4); 2.6760 (0.8); 2.6715 (1.2); 2.6669 (0.8); 2.6623 (0.4); 2.5250 (3.8); 2.5203 (5.8); 2.5116 (72.9); 2.5071 (147.8); 2.5025 (191.3); 2.4979 (134.3); 2.4934 (62.7); 2.3384 (0.4); 2.3339 (0.8); 2.3293 (1.1); 500.1 [M + H].sup.+ 2.3247 (0.8); 2.3202 (0.4); 1.6151 (9.7); 1.5978 (9.7); 1.1531 (0.8); 1.1389 (7.0); 1.1206 (16.0); 1.1021 (6.6); 0.0080 (0.6); −0.0002 (18.0); −0.0085 (0.5) I-181 [00370] .sup.1H-NMR (400.2 MHz, d6-DMSO): δ = 9.5023 (2.4); 9.4844 (2.4); 8.8699 (13.3); 8.8578 (13.6); 8.3534 (3.1); 8.3500 (5.7); 8.3465 (3.4); 8.1586 (3.4); 7.9841 (3.5); 7.4492 (3.5); 7.4371 (6.5); 7.4250 (3.4); 6.2581 (0.7); 6.2458 (2.2); 6.2331 (2.3); 6.2207 (0.6); 6.0716 (0.4); 6.0545 (1.7); 6.0370 (2.7); 6.0195 (1.7); 6.0020 (0.3); 5.7594 (1.5); 3.6369 (0.6); 3.6199 (1.7); 3.6029 (2.5); 3.5859 (1.8); 3.5690 (0.6); 3.3331 (117.8); 2.7519 (12.1); 2.7393 (12.0); 2.6763 (0.6); 2.6719 (0.8); 2.6672 (0.6); 2.5253 (2.3); 2.5205 (3.6); 2.5119 (47.7); 2.5075 (96.8); 2.5029 (127.4); 2.4983 (91.8); 2.4938 (43.6); 2.3342 (0.5); 2.3297 (0.7); 2.3251 (0.5); 1.6161 (9.4); 1.5988 (9.3); 1.1903 (12.0); 1.1754 (16.0); 1.1739 (16.0); 1.1590 (11.7); 514.1 [M + H].sup.+ 0.0081 (0.8); −0.0002 (24.4); −0.0084 (0.7) I-182 [00371] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4938 (2.6); 9.4760 (2.7); 8.8646 (15.5); 8.8525 (16.0); 8.4507 (3.7); 8.4469 (6.6); 8.4432 (3.8); 8.3161 (0.4); 8.1665 (3.7); 8.0945 (3.4); 8.0918 (3.8); 8.0890 (3.9); 8.0822 (9.6); 8.0772 (3.0); 8.0654 (3.0); 8.0603 (10.7); 8.0538 (1.2); 7.7662 (1.2); 7.7598 (10.3); 7.7546 (3.1); 7.7491 (0.4); 7.7428 (2.7); 7.7378 (9.0); 7.7315 (1.1); 7.4409 (4.2); 7.4289 (7.8); 7.4168 (4.1); 6.2435 (0.7); 6.2313 (2.6); 6.2186 (2.6); 6.2061 (0.7); 6.0510 (0.4); 6.0340 (1.9); 6.0165 (3.0); 5.9989 (1.9); 5.9815 (0.4); 3.3533 (0.9); 3.3345 (280.5); 3.3088 (0.4); 2.7495 (13.1); 2.7369 (13.0); 2.6783 (0.6); 2.6737 (0.8); 2.6690 (0.6); 2.5272 (2.3); 2.5225 (3.4); 2.5138 (46.5); 2.5093 (96.1); 2.5047 (126.4); 2.5000 (88.6); 2.4955 (40.9); 2.3361 (0.6); 582.0 [M + H].sup.+ 2.3315 (0.8); 2.3269 (0.6); 1.6083 (10.0); 1.5910 (10.0); −0.0002 (1.5) I-183 [00372] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4327 (2.8); 9.4148 (2.9); 8.8655 (15.6); 8.8534 (16.0); 8.2466 (5.4); 8.0283 (5.1); 7.9826 (3.9); 7.9789 (6.0); 7.9752 (3.2); 7.4460 (4.2); 7.4339 (7.7); 7.4218 (4.0); 6.2442 (0.8); 6.2320 (2.7); 6.2193 (2.7); 6.2069 (0.8); 6.0590 (0.4); 6.0418 (2.1); 6.0242 (3.3); 6.0067 (2.1); 5.9894 (0.4); 3.3325 (117.0); 2.8925 (0.3); 2.7539 (14.7); 2.7413 (14.5); 2.6779 (0.4); 2.6733 (0.5); 2.6687 (0.4); 2.5267 (1.8); 2.5219 (2.9); 2.5133 (32.8); 2.5089 (64.4); 2.5044 (82.5); 2.4998 (58.0); 2.4952 (26.9); 2.3357 (0.4); 2.3312 (0.5); 2.3265 (0.4); 2.2890 (0.6); 2.2763 (1.2); 2.2677 (1.3); 2.2554 (2.4); 2.2429 (1.4); 2.2347 (1.2); 2.2220 (0.6); 496.0 [M + H].sup.+ 2.0875 (1.3); 1.6119 (11.4); 1.5946 (11.3); 1.1358 (1.5); 1.1249(3.4); 1.1194 (3.8); 1.1090 (2.4); 1.1041 (3.5); 1.0985 (3.7); 1.0883 (1.6); 0.8920 (1.8); 0.8814 (4.2); 0.8774 (3.9); 0.8691 (3.9); 0.8648 (4.0); 0.8532 (1.3); 0.0080 (0.6); −0.0002 (16.2); −0.0085 (0.5) I-184 [00373] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4965 (3.1); 9.4786 (3.2); 8.8744 (15.6); 8.8623 (16.0); 8.3994 (4.2); 8.3959 (7.6); 8.3924 (4.4); 8.3154 (0.3); 8.1247 (4.4); 8.0428 (4.5); 7.4539 (4.2); 7.4419 (7.9); 7.4298 (4.1); 6.2518 (0.9); 6.2398 (3.0); 6.2271 (3.0); 6.2146 (0.9); 6.0755 (0.4); 6.0584 (2.2); 6.0409 (3.6); 6.0234 (2.3); 6.0058 (0.5); 3.3288 (201.7); 3.0567 (0.6); 3.0447 (1.4); 3.0370 (1.5); 3.0326 (1.0); 3.0253 (2.8); 3.0169 (1.1); 3.0133 (1.6); 3.0056 (1.5); 2.9936 (0.7); 2.7535 (15.5); 2.7409 (15.4); 2.6808 (0.4); 2.6764 (0.7); 2.6719 (1.0); 2.6674 (0.7); 2.5254 (3.0); 2.5206 (4.4); 2.5119 (55.8); 2.5075 (113.0); 2.5030 (148.2); 2.4984 (106.5); 2.4939 (51.3); 2.3344 (0.7); 2.3298 (0.9); 2.3252 (0.6); 2.3206 (0.3); 2.0749 (8.2); 1.6172 512.2 [M + H].sup.+ (12.2); 1.5999 (12.2); 1.2406 (0.5); 1.2292 (0.6); 1.2170 (2.3); 1.2044 (3.4); 1.1962 (3.9); 1.1851 (2.7); 1.1732 (1.0); 1.1607 (0.7); 1.1475 (0.5); 1.1356 (0.8); 1.1290 (1.1); 1.1140 (4.0); 1.1089 (3.5); 1.0942 (3.8); 1.0876 (3.0); 1.0722 (0.4); 0.0080 (0.9); −0.0002 (28.2); −0.0085 (0.9) I-185 [00374] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4703 (4.2); 9.4524 (4.3); 8.8764 (8.0): 8.8645 (8.0); 8.4339 (6.3); 8.4304 (11.0); 8.4269 (6.3); 8.3159 (0.4); 8.1084 (6.6); 8.1064 (6.3); 8.0660 (6.7); 7.4556 (2.5); 7.4437 (4.4); 7.4318 (2.4); 6.2423 (2.8); 6.2299 (2.8); 6.0773 (0.5); 6.0601 (2.2); 6.0426 (3.3); 6.0252 (2.2); 6.0082 (0.5); 3.3715 (1.0); 3.3538 (52.4); 3.3314 (224.1); 2.7525 (12.8); 2.7402 (13.8); 2.6813 (0.4); 2.6769 (0.8); 2.6725 (1.0); 2.6680 (0.7); 2.6634 (0.4); 2.5259 (3.1); 2.5211 (4.8); 2.5125 (58.4); 2.5081 (116.1); 2.5035 (150.0); 2.4989 (106.5); 2.4944 (50.3); 2.3349 (0.7); 2.3303 (0.9); 2.3257 (0.7); 2.0869 (1.3); 1.6161 (16.0); 1.5988 (15.9); 0.0080 (1.0); −0.0002 (31.3); −0.0085 (1.0) 486.2 [M + H].sup.+ I-186 [00375] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5822 (2.9); 9.5644 (3.0); 8.8714 (15.3); 8.8593 (15.6); 8.5232 (3.8); 8.5190 (6.3); 8.5147 (4.5); 8.4654 (5.8); 8.3989 (5.2); 7.4518 (4.1); 7.4398 (7.6); 7.4277 (4.0); 6.2637 (0.8); 6.2517 (2.8); 6.2390 (2.8); 6.2265 (0.8); 6.0750 (0.4); 6.0575 (2.2); 6.0400 (3.5); 6.0225 (2.2); 6.0052 (0.4); 3.3312 (82.1); 2.7554 (14.9); 2.7428 (14.7); 2.6784 (0.3); 2.6738 (0.5); 2.6692 (0.3); 2.5270 (1.5); 2.5223 (2.4); 2.5137 (27.9); 2.5092 (55.9); 2.5047 (72.8); 2.5001 (52.1); 2.4957 (24.8); 2.3360 (0.3); 2.3316 (0.4); 2.0877 (16.0); 1.6139 (11.8); 1.5965 (11.7); 0.0080 (0.5); −0.0002 (15.3); −0.0084 (0.5) 490.1 [M + H].sup.+ I-187 [00376] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4849 (2.4); 9.4670 (2.5); 8.8611 (15.6); 8.8490 (16.0); 8.4905 (0.3); 8.4034 (3.5); 8.3998 (6.5); 8.3962 (3.6); 8.3616 (0.7); 8.3497 (0.7); 8.3145 (2.0); 8.1298 (3.5); 8.1274 (3.2); 8.0406 (3.5); 7.4458 (4.1); 7.4337 (7.6); 7.4216 (4.0); 6.7560 (0.4); 6.0651 (0.4); 6.0482 (1.9); 6.0306 (2.9); 6.0130 (1.9); 5.9960 (0.4); 5.7460 (7.2); 3.3959 (0.4); 3.3284 (922.2); 3.2987 (0.8); 3.2899 (0.4); 3.0579 (0.6); 3.0457 (1.2); 3.0381 (1.3); 3.0332 (0.8); 3.0263 (2.5); 3.0182 (0.8); 3.0143 (1.3); 3.0065 (1.3); 2.9944 (0.6); 2.6804 (1.2); 2.6759 (2.8); 2.6713 (3.9); 2.6668 (2.7); 2.6621 (1.3); 2.5248 (11.0); 2.5202 (16.0); 2.5115 (220.5); 2.5070 (457.2); 2.5024 (601.8); 2.4977 (422.1); 2.4932 (195.1); 2.3384 (1.2); 2.3338 (2.6); 2.3292 (3.7); 2.3245 (2.6); 2.3200 (1.2); 1.6139 (9.8); 1.5965 (9.8); 1.4662 (0.5); 498.1 [M + H].sup.+ 1.4485 (0.6); 1.2413 (0.4); 1.2287 (0.5); 1.2174 (1.9); 1.2039 (2.8); 1.1958 (3.1); 1.1848 (2.0); 1.1735 (0.8); 1.1615 (0.6); 1.1487 (0.4); 1.1357 (0.7); 1.1284 (0.9); 1.1140(3.3); 1.1086 (2.7); 1.0942 (3.2); 1.0868 (2.3); 1.0723 (0.4); −0.0001 (8.2) I-188 [00377] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4599 (3.3); 9.4420 (3.4); 8.8636 (15.6); 8.8516 (16.0); 8.4389 (4.7); 8.4355 (7.9); 8.4321 (4.6); 8.4182 (0.4); 8.4146 (0.5); 8.4110 (0.3); 8.1330 (0.5); 8.1142 (4.9); 8.0652 (4.9); 7.9532 (1.9); 7.4480 (4.2); 7.4359 (7.9); 7.4239 (4.1); 6.0690 (0.5); 6.0521 (2.4); 6.0345 (3.7); 6.0169 (2.4); 5.9995 (0.5); 5.7491 (9.4); 3.3833 (2.7); 3.3543 (37.6); 3.3318 (177.5); 2.8920 (14.2); 2.7326 (12.0); 2.6769 (0.8); 2.6725 (1.0); 2.6679 (0.7); 2.6634 (0.4); 2.5588 (0.3); 2.5257 (3.7); 2.5123 (65.9); 2.5080 (126.9); 2.5035 (160.2); 2.4990 (113.2); 2.4946 (54.0); 2.3348 (0.7); 2.3303 (1.0); 2.3258 (0.7); 1.6138 (13.0); 1.5964 (12.9); 0.1461 (0.4); 0.0078 (3.0); 0.0000 (77.4); −0.0082 (2.8); −0.1494 (0.4) 472.1 [M + H].sup.+ I-189 [00378] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5510 (2.4); 9.5331 (2.4); 8.8634 (12.7); 8.8513 (13.0); 8.5949 (4.6); 8.5293 (4.0); 8.3311 (4.1); 8.3150 (0.6); 7.4459 (3.5); 7.4338 (6.6); 7.4217 (3.4); 6.0888 (0.4); 6.0716 (1.7); 6.0541 (2.8); 6.0365 (1.8); 6.0190 (0.4); 5.7498 (6.8); 3.5089 (1.9); 3.4905 (6.4); 3.4721 (6.6); 3.4539 (2.1); 3.3283 (189.7); 2.6808 (0.5); 2.6763 (1.1); 2.6717 (1.5); 2.6671 (1.1); 2.6626 (0.5); 2.5252 (4.8); 2.5205 (7.1); 2.5118 (91.1); 2.5073 (185.0); 2.5028 (240.1); 2.4981 (168.5); 2.4936 (78.6); 2.3386 (0.5); 2.3341 (1.1); 2.3296 (1.5); 2.3250 (1.0); 2.3204 (0.5); 1.6224 (9.5); 1.6051 (9.5); 1.1834 (0.3); 1.1650 (0.7); 1.1469 (7.2); 1.1286 (16.0); 1.1101 (6.8); 0.0080 (1.9); −0.0001 (64.9); −0.0085 (1.9) 470.1 [M + H].sup.+ I-190 [00379] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5728 (2.7); 9.5550 (2.7); 8.8924 (15.6); 8.8803 (16.0); 8.4583 (9.7); 8.3145 (2.9); 8.3084 (4.4); 8.2006 (0.4); 7.4791 (4.1); 7.4670 (7.7); 7.4549 (4.0); 6.0945 (0.4); 6.0778 (2.1); 6.0602 (3.3); 6.0425 (2.1); 6.0252 (0.4); 5.7550 (1.7); 3.8100 (0.3); 3.4977 (0.3); 3.3743 (4.8); 3.3577 (12.2); 3.3285 (713.9); 2.6805 (1.3); 2.6761 (2.7); 2.6715 (3.6); 2.6670 (2.7); 2.6625 (1.3); 2.5859 (0.7); 2.5250 (11.7); 2.5203 (17.2); 2.5116 (218.2); 2.5071 (442.9); 2.5026 (576.1); 2.4980 (407.0); 2.4935 (191.2); 2.3385 (1.1); 2.3339 (2.5); 2.3294 (3.5); 2.3249 (2.5); 2.3204 (1.1); 1.9227 (0.5); 1.9079 (4.4); 1.8994 (4.7); 1.8917 (11.6); 1.8837 (4.8); 1.8752 (4.1); 1.8606 (0.6); 1.6466 500.1 [M + H].sup.+ (11.7); 1.6292 (11.5); 1.3427 (0.4); 1.3255 (0.4); 1.2041 (0.3); 1.0224 (0.4); 0.1458 (0.6); 0.0080 (4.9); −0.0002 (161.6); −0.0085 (4.9); −0.1497 (0.7) I-191 [00380] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5353 (0.7); 9.5175 (0.7); 8.9934 (8.8); 8.3398 (0.9); 8.3362 (1.7); 8.3326 (1.0); 8.1482 (1.0); 7.9856 (1.0); 6.0139 (0.5); 5.9963 (0.8); 5.9787 (0.5); 3.6137 (0.5); 3.5967 (0.7); 3.5797 (0.5); 3.3279 (34.4); 2.9513 (16.0); 2.9437 (1.2); 2.5259 (0.7); 2.5211 (1.0); 2.5125 (14.5); 2.5080 (29.8); 2.5034 (38.8); 2.4988 (27.5); 2.4942 (13.1); 1.6273 (2.8); 1.6099 (2.8); 1.1914 (3.6); 1.1753 (5.6); 1.1592 (3.5); 0.0080 (0.9); −0.0002 (28.3); −0.0086 (0.9) 562.0 [M + H].sup.+ I-192 [00381] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5135 (0.8); 9.4957 (0.8); 9.0015 (8.8); 8.4198 (1.0); 8.4162 (1.9); 8.4127 (1.1); 8.1056 (1.1); 8.1034 (1.1); 8.0731 (1.2); 6.0212 (0.6); 6.0036 (0.9); 5.9860 (0.6); 3.3520 (8.9); 3.3282 (25.4); 2.9513 (16.0); 2.5261 (0.6); 2.5213 (0.8); 2.5126 (10.1); 2.5082 (20.4); 2.5037 (26.4); 2.4991 (19.0); 2.4947 (9.1); 1.6274 (3.0); 1.6100 (3.0); 0.0077 (0.8); −0.0002 (20.9); −0.0086 (0.7) 534.0 [M + H].sup.+ I-193 [00382] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5383 (0.7); 9.5207 (0.7); 9.0005 (8.4); 8.3860 (1.0); 8.3824 (1.8); 8.3788 (1.0); 8.1177 (1.0); 8.1154 (1.0); 8.0511 (1.1); 6.0192 (0.5); 6.0017 (0.8); 5.9841 (0.6); 3.3278 (33.7); 3.0455 (0.3); 3.0376 (0.4); 3.0260 (0.7); 3.0139 (0.4); 3.0061 (0.4); 2.9519 (16.0); 2.5257 (0.8); 2.5209 (1.1); 2.5123 (14.0); 2.5078 (27.7); 2.5033 (35.6); 2.4987 (25.0); 2.4942 (11.7); 1.6276 (2.9); 1.6102 (2.9); 1.2178 (0.6); 1.2053 (0.8); 1.1970 (0.9); 1.1858 (0.6); 1.1126 (1.0); 1.1077 (0.8); 1.0930 (0.9); 1.0863 (0.7); 0.0079 (1.0); −0.0002 (29.4); −0.0086 (1.0) 560.0 [M + H].sup.+ I-194 [00383] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5213 (0.7); 9.5033 (0.7); 8.9970 (8.7); 8.3700 (1.0); 8.3663 (1.8); 8.3627 (1.0); 8.1251 (1.0); 8.1227 (0.9); 8.0235 (1.0); 6.0158 (0.5); 5.9982 (0.8); 5.9806 (0.5); 3.4703 (0.5); 3.4519 (1.8); 3.4335 (1.8); 3.4152 (0.6); 3.3305 (96.3); 2.9509 (16.0); 2.6719 (0.3); 2.5255 (1.0); 2.5207 (1.4); 2.5121 (20.6); 2.5076 (42.8); 2.5030 (56.2); 2.4984 (39.8); 2.4938 (18.9); 2.3298 (0.3); 1.6265 (2.8); 1.6091 (2.8); 1.1393 (2.0); 1.1210 (4.5); 1.1026 (1.9); 0.0079 (1.3); −0.0002 (45.0); −0.0086 (1.6) 548.0 [M + H].sup.+ I-195 [00384] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4579 (4.1); 9.4405 (4.2); 8.9719 (7.2); 8.9702 (7.7); 8.9664 (7.7); 8.9646 (7.2); 8.4899 (6.2); 8.4843 (5.8); 8.4683 (6.5); 8.4627 (6.5); 8.3204 (5.9); 8.3166 (11.1); 8.3129 (6.7); 8.2944 (0.4); 8.2303 (6.0); 8.2258 (9.1); 8.2217 (6.1); 8.1538 (6.9); 8.1494 (10.2); 8.1449 (5.7); 7.9424 (7.3); 7.9408 (7.4); 7.9208 (7.0); 7.9191 (7.0); 6.1408 (0.6); 6.1237 (3.0); 6.1063 (4.8); 6.0889 (3.1); 6.0714 (0.6); 3.7961 (0.4); 3.6952 (8.3); 3.6842 (11.8); 3.6715 (9.3); 3.4971 (0.4); 3.3781 (10.3); 3.3660 (12.8); 3.3542 (10.4); 3.3337 (470.7); 3.3255 (60.9); 2.6811 (0.6); 2.6768 (1.2); 2.6722 (1.6); 2.6678 (1.2); 2.6632 (0.6); 2.5257 (5.3); 2.5210 (8.1); 2.5123 (99.0); 2.5078 (201.1); 2.5033 (262.4); 2.4987 (184.6); 2.4941 (86.2); 2.3392 (0.6); 2.3346 (1.2); 2.3301 (1.6); 2.3255 (1.2); 2.3210 (0.5); 1.6200 (16.0); 1.6026 (15.9); 1.2460 (0.9); 1.2300 (1.7); 1.2115 (1.1); 1.2060 (0.5); 1.1948 (0.7); 1.1892 (0.5); 0.8818 (0.3); −0.0002 (1.2) 484.0 [M + H].sup.+ I-196 [00385] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0948 (2.7); 9.0765 (2.8); 8.8821 (15.6); 8.8700 (16.0); 8.3158 (0.7); 7.4785 (4.2); 7.4663 (9.0); 7.4610 (9.1); 7.4570 (9.4); 7.4548 (8.6); 7.2673 (3.7); 6.0095 (0.4); 5.9925 (2.0); 5.9747 (3.1); 5.9569 (2.0); 5.9392 (0.4); 3.3719 (7.3); 3.3281 (385.4); 2.6806 (0.6); 2.6761 (1.4); 2.6716 (1.9); 2.6670 (1.4); 2.6624 (0.6); 2.5251 (5.8); 2.5204 (8.6); 2.5117 (109.9); 2.5072 (225.0); 2.5027 (295.4); 2.4980 (208.3); 2.4935 (97.6); 2.3386 (0.6); 2.3340 (1.3); 2.3294 (1.8); 2.3249 (1.3); 2.3204 (0.6); 2.0610 (0.6); 2.0483 (1.2); 2.0400 (1.2); 2.0275 (2.3); 2.0150 (1.3); 2.0066 (1.2); 1.9941 (0.6); 1.5966 (11.0); 1.5792 (11.3); 1.5520 (14.1); 1.2356 (1.2); 1.0440 (1.3); 1.0339 (3.3); 1.0284 (3.7); 1.0233 (2.0); 1.0187 (2.0); 1.0130 (3.4); 1.0075 (3.5); 0.9979 (1.6); 0.7878 (1.7); 0.7778 (3.2); 0.7748 (3.7); 0.7712 (3.2); 0.7654 (3.4); 0.7626 502.1 [M + H].sup.+ (3.3); 0.7592 (2.6); 0.7508 (1.4); 0.0000 (1.0) I-197 [00386] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2375 (2.8); 9.2211 (2.9); 8.5500 (16.0); 8.3106 (1.3); 7.5654 (6.0); 7.5480 (4.1); 7.2943 (4.0); 5.9711 (0.4); 5.9541 (2.0); 5.9371 (3.0); 5.9200 (2.0); 5.9027 (0.4); 3.6830 (5.7); 3.6722 (8.2); 3.6593 (6.5); 3.3602 (3117.6); 2.8920 (0.4); 2.7324 (0.3); 2.6779 (2.9); 2.6734 (3.9); 2.6689 (2.8); 2.5268 (12.0); 2.5220 (17.5); 2.5134 (235.0); 2.5090 (474.4); 2.5045 (613.6); 2.4999 (431.2); 2.4954 (201.4); 2.3357 (2.7); 2.3312 (3.7); 2.3267 (2.6); 2.0864 (0.6); 2.0734 (1.7); 2.0657 (1.4); 2.0533 (2.5); 2.0408 (1.4); 2.0323 (1.3); 2.0198 (0.7); 1.5948 (10.9); 1.5773 (10.8); 1.0602 (1.4); 1.0492 (4.2); 1.0436(4.5); 1.0333 (2.1); 1.0282 (4.2); 1.0228 (4.2); 1.0125 (1.5); 0.8091 (1.8); 0.7985 (4.6); 0.7934 (4.4); 0.7862 (4.4); 0.7812 (4.7); 0.7698 (1.5); −0.0001 (4.1) 534.4 [M + H].sup.+ I-198 [00387] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3963 (2.7); 9.3780 (2.8); 8.8910 (12.7); 8.8789 (12.9); 8.3139 (0.4); 8.2745 (3.9); 8.2712 (6.6); 8.2676 (3.8); 8.1811 (3.6); 8.1769 (5.9); 8.1730 (3.7); 8.1360 (4.1); 8.1318 (6.0); 8.1276 (3.0); 7.4872 (3.4); 7.4751 (6.4); 7.4630 (3.2); 6.0590 (0.4); 6.0417 (2.0); 6.0241 (3.0); 6.0064 (1.9); 5.9890 (0.4); 3.3769 (8.9); 3.3378 (571.9); 3.3155 (31.0); 2.6763 (1.0); 2.6719 (1.4); 2.6675 (1.0); 2.5251 (4.5); 2.5074 (178.9); 2.5030 (224.6); 2.4985 (159.1); 2.3342 (1.0); 2.3297 (1.4); 2.3253 (1.0); 1.6150 (10.9); 1.5977 (10.9); 1.5536 (16.0); −0.0003 (1.2) 490.2 [M + H].sup.+ I-199 [00388] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO); δ = 9.6342 (2.4); 9.6178 (2.5); 8.5569 (16.0); 8.5274 (8.3); 8.3423 (3.7); 6.0400 (0.4); 6.0229 (1.8); 6.0060 (2.6); 5.9890 (1.8); 5.9714 (0.4); 3.6837 (4.8); 3.6726 (6.8); 3.6599 (5.5); 3.3771 (5.6); 3.3649 (6.8); 3.3534 (4.8); 3.3295 (110.1); 2.6778 (0.5); 2.6732 (0.6); 2.6686 (0.5); 2.5268 (1.9); 2.5221 (2.7); 2.5134 (37.5); 2.5089 (77.3); 2.5043 (101.2); 2.4997 (71.1); 2.4951 (33.3); 2.3358 (0.4); 2.3311 (0.6); 2.3265 (0.4); 1.6303 (9.5); 1.6128 (9.4); −0.0002 (0.8) 546.2 [M + H].sup.+ I-200 [00389] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5125 (2.9); 9.4944 (2.9); 8.8900 (10.5); 8.8779 (10.6); 8.4390 (10.4); 8.3068 (4.5); 7.4830 (2.9); 7.4709 (5.4); 7.4588 (2.8); 6.0807 (0.4); 6.0635 (1.8); 6.0459 (2.8); 6.0284 (1.8); 6.0110 (0.4); 3.3767 (8.5); 3.3296 (193.8); 2.6725 (1.0); 2.5076 (120.5); 2.5037 (151.9); 2.3304 (0.9); 1.6324 (10.3); 1.6151 (10.2); 1.5513 (16.0); −0.0004 (0.7) 514.3 [M + H].sup.+ I-201 [00390] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.5195 (0.2); 9.5086 (0.2); 8.5569 (0.8): 8.3507 (0.2); 8.3482 (0.4); 8.3457 (0.2); 8.2628 (0.2); 8.2598 (0.3); 8.2571 (0.2); 8.1718 (0.2); 8.1689 (0.3); 8.1659 (0.2); 5.9862 (0.1); 5.9748 (0.2); 5.9634 (0.1); 3.6809 (0.3); 3.6732 (0.4); 3.6648 (0.4); 3.3749 (0.4); 3.3667 (0.4); 3.3588 (0.3); 3.3333 (1.7); 3.3208 (16.0); 2.5225 (0.2); 2.5195 (0.2); 2.5163 (0.3); 2.5075 (4.6); 2.5045 (9.8); 2.5014 (13.8); 2.4984 (10.2); 2.4954 (4.9); 1.6084 (0.6); 1.5968 (0.6); −0.0001 (0.2) 522.0 [M + H].sup.+ I-202 [00391] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5232 (2.6); 9.5054 (2.6); 8.8715 (15.6); 8.8594 (16.0); 8.4363 (3.6); 8.4319 (6.0); 8.4277 (4.0); 8.3475 (3.7); 8.3438 (6.5); 8.3401 (3.6); 8.1741 (3.5); 8.1697 (5.9); 8.1654 (3.2); 7.5407 (2.2); 7.4521 (4.1); 7.4400 (7.7); 7.4279 (4.1); 7.4107 (5.0); 7.2808 (2.6); 6.2589 (0.7); 6.2469 (2.4); 6.2341 (2.4); 6.2221 (0.7); 6.0661 (0.4); 6.0490 (2.1); 6.0315 (3.4); 6.0140 (2.1); 5.9966 (0.4); 3.3294 (115.6); 2.7525 (14.9); 2.7399 (14.8); 2.6768 (0.6); 2.6723 (0.8); 2.6678 (0.6); 2.5258 (2.4); 2.5211 (3.7); 2.5124 (48.8); 2.5079 (99.3); 2.5033 (129.1); 2.4987 (90.1); 2.4942 (41.7); 2.3347 (0.6); 2.3302 (0.8); 2.3255 (0.6); 1.6067 472.0 [M + H].sup.+ (11.4); 1.5894 (11.3); −0.0002 (0.5) I-203 [00392] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1562 (2.6); 9.1381 (2.6); 8.8848 (15.6); 8.8728 (16.0); 8.3157 (0.5); 7.4793 (9.1); 7.4744 (11.4); 7.4621 (7.9); 7.4500 (4.0); 7.2697 (3.8); 6.0225 (0.4); 6.0052 (2.0); 5.9875 (3.2); 5.9698 (2.1); 5.9523 (0.4); 3.3717 (4.1); 3.3552 (10.8); 3.3384 (6.2); 3.3275 (203.6); 2.6806 (0.5); 2.6762 (1.0); 2.6716 (1.4); 2.6670 (1.0); 2.6626 (0.5); 2.5251 (4.3); 2.5204 (6.4); 2.5117 (82.3); 2.5072 (168.2); 2.5027 (220.1); 2.4981 (154.2); 2.4935 (71.6); 2.3386 (0.4); 2.3340 (1.0); 2.3294 (1.4); 2.3249 (1.0); 2.3204 (0.4); 2.0631 (0.6); 2.0505 (1.2); 2.0421 (1.3); 2.0383 (0.9); 2.0296 (2.5); 2.0171 (1.4); 2.0087 (1.3); 1.9961 (0.6); 1.9236 (0.5); 1.9085 (4.3); 1.8998 (4.6); 1.8921 (11.2); 1.8843 (4.6); 1.8757 (3.9); 1.8610 (0.5); 1.6131 (11.3); 1.5957 (11.2); 1.3977 (0.3); 1.2351 (0.5); 1.0455 (1.4); 1.0344(4.0); 1.0288 (4.3); 1.0250 (2.1); 1.0184 488.2 [M + H].sup.+ (2.1); 1.0135 (4.1); 1.0079 (4.1); 0.9976 (1.7); 0.7945 (1.8); 0.7838 (4.6): 0.7786 (4.6); 0.7716 (4.3); 0.7663 (5.0); 0.7549 (1.4); −0.0002 (0.9) I-204 [00393] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2525 (0.8); 9.2350 (0.8); 8.9664 (1.4); 8.9647 (1.5); 8.9609 (1.5); 8.9591 (1.4); 8.4866 (1.2); 8.4810 (1.2); 8.4650 (1.3); 8.4593 (1.3); 7.9377 (1.5); 7.9360 (1.5); 7.9161 (1.5); 7.9143 (1.5); 7.8973 (0.8); 7.8936 (2.0); 7.8895 (3.0); 7.8855 (2.2); 7.8819 (0.7); 7.7472 (1.3); 7.7426 (2.2); 7.7379 (1.1); 6.0952 (0.6); 6.0778 (1.0); 6.0604 (0.6); 3.6930 (1.6); 3.6821 (2.3); 3.6693 (1.8); 3.3777 (1.9); 3.3656 (2.3); 3.3540 (1.6); 3.3292 (53.3); 2.5255 (0.8); 2.5208 (1.1); 2.5122 (15.5); 2.5077 (31.6); 2.5031 (41.4); 2.4984 (28.9); 2.4939 (13.3); 1.7117 (16.0); 1.6139 (3.2); 1.5965 (3.2); 1.3973 (0.8); −0.0002 (0.5) 505.4 [M + H].sup.+ I-205 [00394] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5223 (4.2); 9.5048 (4.3); 8.9322 (6.6); 8.9305 (7.4); 8.9267 (7.2); 8.9249 (7.2); 8.4477 (7.8); 8.4464 (7.8); 8.4424 (16.0); 8.4388 (6.4); 8.4263 (6.1); 8.4207 (6.0); 8.3142 (1.0); 8.1679 (5.8); 8.1656 (5.3); 8.0559 (5.9); 7.8309 (7.0); 7.8294 (7.3); 7.8093 (6.7); 7.8077 (7.0); 6.1317 (0.6); 6.1150 (2.9); 6.0976 (4.7); 6.0803 (3.0); 6.0632 (0.6); 5.9938 (11.2); 3.3767 (1.0); 3.3328 (847.2); 3.0670 (0.8); 3.0551 (1.8); 3.0474 (2.0); 3.0356 (3.8); 3.0274 (1.4); 3.0236 (2.0); 3.0159 (2.0); 3.0040 (0.9); 2.6810 (0.8); 2.6766 (1.6); 2.6721 (2.3); 2.6675 (1.6); 2.6630 (0.8); 2.5256 (6.7); 2.5209 (10.0); 2.5122 (132.9); 2.5077 (274.4); 2.5031 (361.2); 2.4985 (254.9); 2.4940 (119.1); 2.3390 (0.7); 2.3345 (1.6); 2.3299 (2.2); 2.3253 (1.6); 2.3210 (0.8); 2.0745 (1.3); 1.6160 (15.4); 1.5986 (15.3); 1.2481 (0.6); 1.2382 (0.7); 1.2245 (2.7); 1.2102 (4.2); 1.2030 (5.5); 1.1915 (3.6); 1.1800 (1.2); 1.1681 (0.8); 1.1543 (0.6); 1.1416 (1.0); 1.1344 (1.3); 1.1191 (5.3); 1.1142 (4.6); 1.0994 (5.0); 1.0940 (4.1); 1.0768 (0.6); 0.0000 522.2 [M + H].sup.+ (1.5) I-206 [00395] .sup.13C-NMR (150.9 MHz, d.sub.6-DMSO): δ = 164.7995 (3.9); 164.2742 (4.6); 162.2692 (3.8); 159.7592 (4.1); 152.6531 (4.0); 148.5649 (1.8); 148.5538 (1.8); 147.5188 (3.8); 135.6386 (3.5); 123.2074 (4.4); 122.7683 (0.4); 121.5501 (2.7); 121.0678 (1.2); 119.3674 (1.1); 117.6668 (0.3); 116.9344 (3.4); 112.6459 (2.3); 101.2059 (4.2); 43.7290 (4.8); 40.3528 (0.3); 40.2358 (5.7); 40.1161 (26.7); 39.9775 (78.8); 39.8386 (154.0); 39.6995 (180.2); 39.5604 (152.5); 39.4213 (76.3); 39.2822 (24.8); 29.2656 (7.0); 18.2601 (7.0); 18.1946 (0.2); 15.1684 (6.2); 10.3230 (7.0); 10.2488 (6.9); 0.2724 (0.5) 478.0 [M + H].sup.+ I-207 [00396] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.2978 (0.1); 9.2869 (0.1); 8.5188 (0.5); 7.9606 (0.1); 7.9580 (0.2); 7.9551 (0.2); 7.9474 (0.2); 7.9446 (0.2); 7.9420 (0.1); 7.7620 (0.1); 7.7589 (0.2); 7.7558 (0.1); 5.9072 (0.1); 3.3362 (16.0); 2.7503 (0.5); 2.7420 (0.5); 2.5096 (1.3); 2.5066 (2.9); 2.5035 (4.0); 2.5005 (2.9); 2.4975 (1.3); 1.7308 (0.1); 1.7229 (1.2); 1.7218 (1.2); 1.5935 (0.4); 1.5819 (0.4); 0.0053 (0.1); −0.0001 (4.2); −0.0057 (0.1) 478.0 [M + H].sup.+ I-208 [00397] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6167 (2.7); 9.6004 (2.8); 8.5389 (9.7); 8.5240 (16.0); 8.3434 (4.3); 6.8834 (0.8); 6.8716 (2.5); 6.8592 (2.5); 6.8470 (0.8); 5.9915 (0.4); 5.9740 (2.0); 5.9571 (3.0); 5.9401 (2.0); 5.9225 (0.4); 3.3327 (130.4); 2.7526 (13.6); 2.7402 (13.5); 2.6780 (0.4); 2.6735 (0.6); 2.6691 (0.4); 2.5270 (1.9); 2.5222 (3.0); 2.5136 (36.3); 2.5092 (72.2); 2.5046 (92.5); 2.5000 (65.0); 2.4956 (30.5); 2.3361 (0.4); 2.3314 (0.6); 2.3268 (0.4); 2.0761 (10.4); 1.6200 (10.7); 1.6025 (10.6) 490.1 [M + H].sup.+ I-209 [00398] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.3705 (0.1); 9.3596 (0.1); 8.5149 (0.6); 8.1707 (0.2); 8.1681 (0.3); 8.1655 (0.2); 7.9036 (0.1); 7.8336 (0.2); 7.8320 (0.1); 6.8621 (0.1); 6.8537 (0.1); 5.8922 (0.1); 3.3229 (16.0); 2.7484 (0.6); 2.7401 (0.6); 2.5237 (0.1); 2.5205 (0.1); 2.5174 (0.1); 2.5086 (2.3); 2.5056 (5.2); 2.5026 (7.3); 2.4995 (5.2); 2.4965 (2.4); 1.5831 (0.5); 1.5714 (0.5); 0.0054 (0.3); −0.0001 (9.0); −0.0057 (0.3) 518.0 [M + H].sup.+ I-210 [00399] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.3050 (0.3); 9.2941 (0.3); 8.5152 (1.2); 8.0683 (1.1); 8.0653 (1.6); 8.0505 (0.4); 8.0477 (0.5); 8.0450 (0.2); 6.8630 (0.2); 6.8546 (0.2); 5.8873 (0.2); 5.8759 (0.3); 5.8645 (0.2); 5.7526 (0.2); 3.3234 (16.0); 2.7478 (1.3); 2.7395 (1.3); 2.5239 (0.2); 2.5209 (0.2); 2.5178 (0.2); 2.5089 (3.3); 2.5060 (7.2); 2.5029 (10.0); 2.4999 (7.3); 2.4969 (3.4); 1.5703 (1.0); 1.5587 (1.0); 0.0053 (0.3); −0.0001 (8.8); −0.0057 (0.3) 511.9 [M + H].sup.+ I-211 [00400] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5379 (4.1); 9.5200 (4.2); 8.9463 (0.3); 8.8675 (12.8); 8.8555 (13.0); 8.7237 (0.4); 8.6507 (2.6); 8.6414 (8.2); 8.6058 (0.3); 8.5044 (8.6); 8.4723 (2.0); 8.4033 (0.7); 8.3880 (7.3); 8.3646 (0.8); 8.3526 (0.8); 8.3491 (0.4); 8.3371 (0.4); 8.3156 (0.6); 7.4502 (4.4); 7.4382 (8.2); 7.4261 (4.2); 6.7581 (0.4); 6.0895 (0.6); 6.0725 (2.8); 6.0550 (4.4); 6.0374 (2.8); 6.0203 (0.6); 5.7507 (9.2); 5.7121 (0.5); 3.4140 (13.9); 3.3915 (2.9); 3.3776 (47.3); 3.3278 (115.4); 3.1752 (0.4); 3.1630 (0.4); 2.6764 (1.3); 2.6718 (1.8); 2.6674 (1.3); 2.6626 (0.6); 2.5252 (6.2); 2.5203 (9.9); 2.5118 (111.5); 2.5074 (222.3); 2.5029 (287.6); 2.4983 456.1 [M + H].sup.+ (204.4); 2.4939 (97.3); 2.3383 (0.6); 2.3342 (1.3); 2.3297 (1.8); 2.3252 (1.3); 2.3206 (0.6); 1.6221 (16.0); 1.6048 (15.9); 1.4722 (0.7); 1.4543 (0.7); 1.3961 (1.2); 1.3814 (2.2); 1.3162 (1.6); 1.2700 (0.4); 1.2519 (0.4); 1.2428 (0.4); 1.2337 (0.5); −0.0002 (0.9) I-212 [00401] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.5736 (0.2); 9.5627 (0.2); 8.5209 (1.0); 8.4946 (0.2); 8.4922 (0.5); 8.4899 (0.3); 8.1680 (0.3); 8.0981 (0.3); 6.8681 (0.2); 6.8598 (0.2); 5.9552 (0.1); 5.9439 (0.2); 5.9325 (0.2); 3.3659 (2.2); 3.3224 (16.0); 2.7516 (1.0); 2.7433 (1.0); 2.5236 (0.1); 2.5206 (0.2); 2.5175 (0.2); 2.5086 (3.1); 2.5056 (6.7); 2.5026 (9.4); 2.4995 (6.7); 2.4965 (3.1); 1.6116 (0.8); 1.6000 (0.8); 1.2346 (0.2); 0.0053 (0.2); −0.0001 (8.2); −0.0057 (0.3) 516.0 [M + H].sup.+ I-213 [00402] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 9.4660 (0.5); 9.4541 (0.6); 8.8573 (2.4); 8.8493 (2.5); 8.3897 (0.6); 8.3874 (1.2); 8.3850 (0.8); 8.1377 (0.7); 8.0139 (0.7); 7.4389 (0.6); 7.4308 (1.2); 7.4228 (0.6); 6.0441 (0.4); 6.0324 (0.6); 6.0207 (0.4); 5.7411 (1.7); 3.4635 (0.4); 3.4513 (1.2); 3.4390 (1.2); 3.4268 (0.4); 3.3247 (16.0); 2.8919 (0.2); 2.6909 (1.5); 2.6180 (0.1); 2.6150 (0.2); 2.6119 (0.1); 2.5239 (0.3); 2.5209 (0.4); 2.5178 (0.4); 2.5089 (7.8); 2.5059 (17.5); 2.5029 (24.7); 2.4999 (18.6); 2.4970 (9.0); 2.3900 (0.1); 2.3867 (0.2); 2.3843 (0.1); 1.6112 (2.0); 1.5997 (2.0); 1.2431 (0.3); 1.1369 (1.4); 1.1247 (3.0); 1.1124 (1.4); 0.0053 (0.2); −0.0001 (5.0); −0.0057 (0.2) 486.1 [M + H].sup.+ I-214 [00403] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5213 (2.6); 9.5039 (2.6); 8.9215 (4.2); 8.9199 (4.4); 8.9160 (4.5); 8.9142 (4.2); 8.4444 (3.5); 8.4388 (3.3); 8.4227 (3.7); 8.4171 (3.7); 8.3970 (3.4); 8.3935 (6.1); 8.3901 (3.5); 8.3149 (0.7); 8.1973 (3.6); 7.9926 (3.7); 7.8276 (4.5); 7.8260 (4.4); 7.8059 (4.2); 7.8043 (4.2); 6.1288 (0.4); 6.1116 (1.8); 6.0943 (2.8); 6.0769 (1.8); 6.0600 (0.4); 5.9958 (7.0); 3.6449 (0.6); 3.6280 (1.9); 3.6110 (2.6); 3.5940 (1.9); 3.5771 (0.7); 3.3602 (0.4); 3.3253 (298.9); 2.6902 (1.1); 2.6805 (0.7); 2.6759 (1.4); 2.6714 (2.0); 2.6669 (1.5); 2.6623 (0.7); 2.5249 (6.6); 2.5202 (9.8); 2.5115 (111.4); 2.5070 (223.1); 2.5024 (295.0); 2.4979 (218.5); 2.4934 (107.6); 2.3384 (0.7); 2.3339 (1.4); 2.3293 (2.0); 2.3248 (1.4); 2.3204 (0.7); 1.6155 (9.4); 1.5981 (9.4); 1.4345 (0.4); 1.1980 (12.3); 1.1836 (16.0); 1.1814 (16.0); 1.1671 (12.1); 0.1460 (1.2); 0.0081 (9.5); −0.0001 (287.6); −0.0084 (10.2); −0.1495 (1.2) 524.0 [M + H].sup.+ I-215 [00404] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4874 (2.5); 9.4695 (2.6); 8.8559 (15.2); 8.8438 (15.7); 8.3595 (3.4); 8.3559 (6.3); 8.3523 (3.6); 8.3150 (1.0); 8.1636 (3.5); 8.1613 (3.2); 7.9783 (3.5); 7.4394 (4.0); 7.4273 (7.5); 7.4152 (3.9); 6.0644 (0.4); 6.0472 (1.8); 6.0296 (2.9); 6.0121 (1.8); 5.9946 (0.4); 5.7477 (7.3); 3.8306 (1.3); 3.6364 (0.7); 3.6195 (1.9); 3.6025 (2.7); 3.5855 (2.0); 3.5685 (0.7); 3.3258 (420.1); 2.6804 (0.8); 2.6759 (1.9); 2.6713 (2.6); 2.6667 (1.9); 2.6621 (0.9); 2.5248 (8.6); 2.5201 (12.2); 2.5114 (139.1); 2.5069 (284.2); 2.5022 (380.2); 2.4976 (281.2); 2.4931 (137.4); 2.3383 (0.8); 2.3337 (1.8); 2.3291 (2.5); 2.3245 (1.8); 2.3200 (0.8); 1.6137 (9.7); 1.5963 (9.6); 1.1922 (12.9); 1.1778 500.0 [M + H].sup.+ (16.0); 1.1755 (16.0); 1.1612 (12.4); 0.1459 (1.8); 0.0219 (0.4); 0.0081 (14.0); −0.0002 (429.0); −0.0085 (14.4); −0.0251 (0.4); −0.1495 (1.8) I-216 [00405] .sup.1H-NMR (600.1 MHz, d.sub.6-DMSO): δ = 8.8495 (0.2); 8.8415 (0.2); 7.4260 (0.1); 5.7100 (0.1); 3.3214 (16.0); 2.5229 (0.2); 2.5198 (0.2); 2.5167 (0.2); 2.5079 (3.3); 2.5049 (7.4); 2.5018 (10.5); 2.4987 (7.5); 2.4956 (3.3); 1.5801 (0.2); 1.5685 (0.2) 434.2 [M + H].sup.+ I-217 [00406] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6580 (2.6); 9.6416 (2.7); 8.6980 (4.8); 8.5662 (4.2); 8.5266 (16.0); 8.4225 (4.2); 8.4213 (4.2); 6.8886 (0.7); 6.8766 (2.4); 6.8642 (2.4); 6.8517 (0.7); 6.0006 (0.4); 5.9837 (1.8); 5.9668 (2.7); 5.9497 (1.8); 5.9325 (0.4); 3.3909 (28.3); 3.3272 (115.6); 2.7533 (12.2); 2.7409 (12.2); 2.6767 (0.5); 2.6720 (0.7); 2.6674 (0.5); 2.5256 (2.4); 2.5209 (3.5); 2.5122 (40.7); 2.5077 (80.8); 2.5031 (105.9); 2.4984 (77.5); 2.4939 (37.4); 2.3346 (0.5); 2.3299 (0.7); 2.3253 (0.5); 2.0747 (3.1); 1.6238 (9.4); 1.6064 (9.4); 1.2552 (0.6); 1.2398 (1.0); 1.2238 (0.6); 0.1459 (0.5); 0.0080 (4.0); −0.0002 (115.6); −0.0086 (3.7); −0.1495 (0.5) 500.0 [M + H].sup.+ I-218 [00407] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6769 (3.1); 9.6607 (3.2); 8.5714 (3.9); 8.5674 (6.5); 8.5630 (4.6); 8.5252 (6.0); 8.5145 (16.0); 8.4330 (3.2); 8.4292 (5.2); 6.8953 (0.8); 6.8834 (2.9); 6.8709 (2.9); 6.8587 (0.8); 5.9716 (0.4); 5.9542 (2.1); 5.9373 (3.1); 5.9204 (2.1); 5.9032 (0.4); 3.3279 (167.1); 2.7544 (13.9); 2.7420 (13.9); 2.6770 (0.7); 2.6724 (0.9); 2.6678 (0.7); 2.5259 (3.0); 2.5211 (4.4); 2.5124 (51.9); 2.5080 (102.7); 2.5034 (134.8); 2.4988 (99.8); 2.4943 (49.2); 2.3347 (0.6); 2.3303 (0.9); 2.3256 (0.6); 1.6114 (11.0); 1.5939 (11.0); 0.1460 (0.6); 0.0080 (4.6); −0.0002 (132.1); −0.0084 (5.0); −0.1495 (0.6) 520.1 [M + H].sup.+ I-219 [00408] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3799 (3.6); 9.3636 (3.8); 8.5182 (16.0); 8.2801 (8.5); 8.2766 (6.0); 8.2628 (4.2); 8.2582 (6.8); 8.2547 (4.4); 8.2305 (5.6); 8.2264 (7.0); 8.2219 (3.9); 6.8881 (1.0); 6.8764 (3.3); 6.8639 (3.3); 6.8519 (1.0); 5.9310 (0.5); 5.9140 (2.4); 5.8970 (3.6); 5.8799 (2.4); 5.8626 (0.5); 3.9031 (1.0); 3.3275 (125.4); 2.7502 (15.9); 2.7379 (15.9); 2.6764 (0.6); 2.6720 (0.8); 2.6676 (0.6); 2.5253 (2.9); 2.5076 (94.7); 2.5031 (123.2); 2.4986 (93.2); 2.3344 (0.6); 2.3299 (0.8); 2.3254 (0.6); 2.0750 (6.9); 1.5871 (12.9); 1.5697 (12.9); 0.1459 (0.5); 0.0078 (4.0); −0.0002 (98.7); −0.0085 (4.1); −0.1495 (0.5) 413.0 [M + H].sup.+ I-220 [00409] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5504 (3.6); 9.5327 (3.7); 8.9502 (5.8); 8.9486 (6.2); 8.9448 (6.2); 8.9431 (5.9); 8.4787 (12.1); 8.4647 (5.1); 8.4591 (4.8); 8.4430 (5.3); 8.4374 (5.3); 8.3208 (5.4); 7.9303 (6.2); 7.9288 (6.1); 7.9086 (5.9); 7.9070 (5.8); 6.1572 (0.5); 6.1402 (2.6); 6.1227 (4.1); 6.1052 (2.6); 6.0877 (0.5); 3.5689 (6.3); 3.3977 (9.3); 3.3308 (464.2); 2.6812 (0.6); 2.6769 (1.3); 2.6724 (1.9); 2.6678 (1.4); 2.6632 (0.6); 2.5258 (6.0); 2.5211 (8.6); 2.5124 (108.2); 2.5080 (218.9); 2.5034 (286.3); 2.4988 (205.9); 2.4943 (98.6); 2.3393 (0.6); 2.3348 (1.3); 2.3302 (1.8); 2.3257 (1.3); 2.3213 (0.6); 1.6293 (13.8); 1.6119 (13.8); 1.5520 (16.0); 0.1459 (1.1); 0.0079 (8.1); −0.0002 (258.9); −0.0086 (8.7); −0.1495 (1.1) 538.1 [M + H].sup.+ I-221 [00410] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1396 (3.3); 9.1218 (3.4); 8.9390 (5.5); 8.9376 (6.2); 8.9336 (5.9); 8.9320 (5.9); 8.4594 (4.6); 8.4538 (4.4); 8.4378 (4.9); 8.4321 (4.9); 8.3154 (0.4); 7.9201 (5.7); 7.9187 (6.0); 7.8985 (5.4); 7.8969 (5.6); 7.5105 (7.2); 7.5069 (5.7); 7.5001 (4.4); 7.4974 (4.8); 7.2783 (4.6); 6.0868 (0.5); 6.0697 (2.4); 6.0521 (3.8); 6.0345 (2.4); 6.0173 (0.5); 3.3945 (9.0); 3.3601 (0.7); 3.3295 (282.1); 2.6808 (0.5); 2.6765 (1.0); 2.6720 (1.4); 2.6674 (1.0); 2.6629 (0.5); 2.5254 (4.4); 2.5207 (6.8); 2.5120 (82.1); 2.5076 (164.0); 2.5030 (213.2); 2.4984 (153.8); 2.4939 (74.3); 2.3390 (0.4); 2.3344 (1.0); 2.3298 (1.3); 2.3253 (1.0); 2.3207 (0.4); 2.0748 (1.0); 2.0620 (1.4); 2.0536 (1.5); 2.0411 (2.8); 2.0286 (1.6); 2.0202 (1.5); 2.0077 (0.8); 1.5960 (13.3); 1.5786 (13.9); 1.5531 (16.0); 1.0531 (1.7); 1.0421 (4.6); 1.0365 (4.9); 1.0326 (2.6); 1.0262 (2.6); 1.0212 (4.7); 526.1 [M + H].sup.+ 1.0156 (4.7); 1.0054 (1.9); 0.7998 (2.0); 0.7893 (5.2); 0.7840 (5.1); 0.7770 (4.9); 0.7718 (5.4); 0.7605 (1.6); 0.1458 (0.8); 0.0079 (6.1); −0.0002 (175.2); −0.0086 (5.9); −0.1497 (0.8) I-222 [00411] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4424 (3.3); 9.4247 (3.4); 8.9532 (5.5); 8.9517 (5.8); 8.9477 (5.8); 8.9461 (5.5); 8.4649 (4.6); 8.4593 (4.4); 8.4432 (4.9); 8.4376 (4.9); 8.3205 (4.5); 8.3167 (8.6); 8.3131 (5.4); 8.2295 (4.6); 8.2251 (7.2); 8.2209 (4.8); 8.1536 (5.0); 8.1492 (7.8); 8.1448 (4.2); 7.9300 (5.9); 7.9286 (5.8); 7.9084 (5.5); 7.9069 (5.5); 6.1395 (0.5); 6.1226 (2.4); 6.1051 (3.8); 6.0876 (2.4); 6.0701 (0.5); 3.3996 (8.9); 3.3654 (1.2); 3.3357 (467.2); 3.3255 (44.4); 2.6814 (0.4); 2.6769 (1.0); 2.6724 (1.4); 2.6678 (1.0); 2.6633 (0.5); 2.5259 (4.1); 2.5212 (6.1); 2.5124 (79.2); 2.5080 (160.6); 2.5034 (210.3); 2.4988 (151.0); 2.4943 (72.3); 2.3394 (0.5); 2.3348 (1.0); 2.3302 (1.3); 2.3257 (1.0); 2.3212 (0.5); 1.6121 (12.9); 1.5947 (13.0); 1.5549 (16.0); 0.1459 (0.8); 0.0080 (5.8); −0.0002 (182.6); −0.0085 (5.8); −0.0164 (0.4); −0.0200 (0.3); −0.1496 (0.8) 514.2 [M + H].sup.+ I-223 [00412] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4855 (1.4); 9.4679 (1.4); 8.9806 (16.0); 8.4468 (2.0); 8.4432 (3.4); 8.4396 (1.9); 8.3151 (0.4); 8.1264 (2.0); 8.1241 (1.8); 8.0726 (2.0); 6.3404 (0.4); 6.3290 (1.3); 6.3163 (1.3); 6.3041 (0.4); 6.0180 (1.0); 6.0006 (1.6); 5.9830 (1.0); 3.3556 (15.9); 3.3278 (174.0); 2.7481 (6.6); 2.7355 (6.6); 2.6806 (0.4); 2.6759 (0.8); 2.6715 (1.0); 2.6669 (0.7); 2.6626 (0.4); 2.5249 (3.8); 2.5202 (5.8); 2.5115 (59.4); 2.5071 (115.7); 2.5025 (150.0); 2.4979 (108.9); 2.4934 (52.3); 2.3339 (0.7); 2.3293 (0.9); 2.3248 (0.7); 1.6068 (5.2); 1.5895 (5.1); 0.1460 (0.5); 0.0080 (4.6); −0.0002 (128.0); −0.0085 (4.2); −0.1495 (0.5) 520.0 [M + H].sup.+ I-224 [00413] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6120 (4.0); 9.5944 (4.1); 8.9554 (7.1); 8.9537 (7.6); 8.9499 (7.6); 8.9480 (7.1); 8.4933 (13.8); 8.4640 (6.2); 8.4583 (5.9); 8.4423 (6.6); 8.4366 (6.6); 8.3234 (7.0); 8.1753 (0.4); 7.9317 (7.4); 7.9301 (7.3); 7.9101 (7.0); 7.9084 (6.9); 6.1772 (0.6); 6.1601 (3.0); 6.1426 (4.8); 6.1251 (3.0); 6.1079 (0.6); 3.4498 (0.3); 3.3842 (5.5); 3.3676 (14.1); 3.3512 (6.1); 3.3277 (246.2); 2.6775 (3.3); 2.6725 (2.1); 2.6679 (1.4); 2.6634 (0.7); 2.5260 (6.5); 2.5213 (9.6); 2.5126 (106.1); 2.5081 (211.9); 2.5035 (278.3); 2.4989 (202.3); 2.4943 (97.5); 2.3394 (0.6); 2.3349 (1.3); 2.3303 (1.8); 2.3258 (1.2); 2.3212 (0.6); 1.9258 (0.7); 1.9112 (6.0); 1.9025 (6.7); 1.8949 (15.6); 1.8872 (6.6); 1.8785 (5.5); 1.8635 (0.7); 1.6422 (16.0); 1.6247 (15.9); 1.2079 (1.9); 1.1915 (2.0); 1.1852 524.1 [M + H].sup.+ (1.6); 1.1673 (0.6); 0.1460 (0.8); 0.0080 (6.9); −0.0001 (205.3); −0.0085 (6.5); −0.1496 (0.8) I-225 [00414] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5012 (4.1); 9.4836 (4.3); 8.9579 (7.0); 8.9563 (7.2); 8.9524 (7.6); 8.9507 (7.0); 8.4632 (5.8); 8.4575 (5.5); 8.4415 (6.2); 8.4358 (6.2); 8.3295 (5.6); 8.3257 (10.6); 8.3220 (6.3); 8.3155 (0.6); 8.2391 (5.8); 8.2346 (8.8); 8.2305 (6.0); 8.1541 (6.3); 8.1497 (9.7); 8.1452 (5.5); 7.9302 (7.3); 7.9287 (7.2); 7.9085 (6.9); 7.9070 (6.8); 6.1580 (0.6); 6.1406 (3.0); 6.1231 (4.7); 6.1056 (3.0); 6.0882 (0.6); 3.3882 (5.7); 3.3718 (15.0); 3.3556 (6.2); 3.3288 (192.6); 2.6770 (0.7); 2.6724 (1.0); 2.6679 (0.7); 2.6634 (0.3); 2.5259 (3.2); 2.5212 (4.7); 2.5125 (54.7); 2.5080 (109.7); 2.5035 (144.7); 2.4989 (106.6); 2.4944 (52.2); 2.3348 (0.6); 2.3303 (0.9); 2.3258 (0.7); 1.9284 (0.7); 1.9133 (6.1); 1.9046 (6.8); 1.8970 (16.0); 1.8896 (6.9); 1.8806 (5.6); 1.8661 (0.7); 1.6250 (15.6); 1.6076 (15.5); 500.1 [M + H].sup.+ 0.1460 (0.4); 0.0080 (3.3); −0.0002 (96.8); −0.0085 (3.1); −0.1496 (0.4) I-226 [00415] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1022 (1.2); 9.0844 (1.3); 8.9702 (16.0); 7.5144 (3.0); 7.5107 (3.0); 7.5050 (1.8); 7.5025 (1.5); 7.2725 (1.7); 6.3164 (0.3); 6.3044 (1.2); 6.2918 (1.2); 6.2793 (0.3); 5.9594 (0.9); 5.9418 (1.4); 5.9242 (0.9); 3.3303 (41.3); 2.7465 (6.2); 2.7339 (6.2); 2.5263 (0.9); 2.5216 (1.2); 2.5129 (14.0); 2.5084 (27.9); 2.5037 (36.7); 2.4991 (26.7); 2.4946 (12.8); 2.0561 (0.5); 2.0477 (0.6); 2.0438 (0.4); 2.0353 (1.1); 2.0265 (0.4); 2.0227 (0.6); 2.0144 (0.6); 1.5809 (4.9); 1.5635 (4.8); 1.3975 (8.0); 1.0499 (0.6); 1.0389 (1.8); 1.0333 (1.9); 1.0294 (0.8); 1.0228 (0.8); 1.0179 (1.8); 1.0123 (1.9); 1.0021 (0.7); 0.7980 (0.8); 0.7876 (2.0); 0.7823 (1.9); 0.7751 (1.9); 0.7701 (2.0); 0.7588 (0.6); 0.0079 (0.9); −0.0002 (27.4); −0.0086 (0.9) 482.0 [M + H].sup.+ I-227 [00416] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5250 (1.2); 9.5073 (1.3); 8.9812 (16.0); 8.4882 (4.2); 8.3173 (1.9); 6.3376 (0.4); 6.3253 (1.2); 6.3126 (1.2); 6.2999 (0.3); 6.0284 (0.9); 6.0109 (1.4); 5.9935 (0.9); 3.3285 (47.2); 2.7484 (6.2); 2.7358 (6.2); 2.6728 (0.4); 2.5263 (1.3); 2.5217 (2.0); 2.5129 (20.2); 2.5084 (40.1); 2.5038 (52.5); 2.4992 (38.5); 2.4947 (18.8); 2.3307 (0.3); 1.6123 (4.9); 1.5949 (4.8); 1.3976 (8.8); 0.0080 (1.3); −0.0002 (37.0); −0.0085 (1.2) 494.0 [M + H].sup.+ I-228 [00417] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4079 (1.4); 9.3901 (1.4); 8.9814 (16.0); 8.3188 (2.0); 8.3150 (3.7); 8.3112 (2.3); 8.2261 (2.0); 8.2216 (3.1); 8.2176 (2.2); 8.1458 (2.2); 8.1414 (3.3); 8.1370 (2.0); 6.3408 (0.4); 6.3290 (1.3); 6.3163 (1.3); 6.3039 (0.4); 6.0058 (1.0); 5.9884 (1.6); 5.9708 (1.0); 3.3744 (0.4); 3.3382 (169.9); 3.3243 (17.2); 2.7478 (6.5); 2.7353 (6.5); 2.6771 (0.3); 2.6727 (0.4); 2.6682 (0.3); 2.5260 (1.4); 2.5212 (2.2); 2.5125 (26.6); 2.5081 (52.9); 2.5036 (69.3); 2.4990 (52.4); 2.4946 (26.5); 2.3303 (0.4); 1.5944 (5.3); 1.5771 (5.3); 0.0079 (1.9); −0.0002 (52.9); −0.0085 (1.9) 470.0 [M + H].sup.+ I-229 [00418] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5392 (0.7); 9.5211 (0.7); 8.5148 (1.2); 8.5132 (1.3); 8.5091 (1.3); 8.5074 (1.2); 8.4758 (2.4); 8.3151 (0.8); 8.3100 (1.1); 8.0617 (0.9); 8.0560 (0.9); 8.0406 (1.1); 8.0348 (1.1); 7.8266 (1.3); 7.8250 (1.3); 7.8055 (1.1); 7.8038 (1.2); 6.1398 (0.5); 6.1221 (0.8); 6.1046 (0.5); 3.3277 (147.4); 3.0013 (1.5); 2.9539 (16.0); 2.9207 (1.6); 2.6760 (0.6); 2.6714 (0.8); 2.6668 (0.6); 2.5249 (3.1); 2.5202 (4.7); 2.5115 (50.4); 2.5070 (100.0); 2.5024 (130.8); 2.4978 (94.3); 2.4933 (45.0); 2.3338 (0.6); 2.3293 (0.8); 2.3247 (0.6); 1.6416 (2.8); 1.6242 (2.8); 0.1459 (0.4); 0.0080 (3.6); −0.0002 (101.9); −0.0085 (3.2); −0.1496 (0.4) 544.2 [M + H].sup.+ I-230 [00419] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2024 (4.0); 9.1848 (4.2); 8.9430 (6.9); 8.9415 (7.3); 8.9376 (7.4); 8.9359 (6.9); 8.4575 (5.6); 8.4519 (5.3); 8.4359 (6.0); 8.4302 (6.0); 8.3161 (0.4); 7.9218 (7.3); 7.9203 (7.1); 7.9002 (6.9); 7.8986 (6.6); 7.5235 (8.7); 7.5200 (6.2); 7.5105 (5.4); 7.5078 (5.9); 7.2809 (5.7); 6.1039 (0.6); 6.0869 (3.0); 6.0694 (4.7); 6.0519 (3.0); 6.0347 (0.6); 3.3820 (5.6); 3.3656 (14.0); 3.3492 (6.1); 3.3298 (185.0); 2.6772 (0.8); 2.6727 (1.1); 2.6682 (0.8); 2.6638 (0.4); 2.5262 (3.6); 2.5214 (5.2); 2.5127 (62.9); 2.5083 (124.1); 2.5037 (161.4); 2.4991 (117.7); 2.4947 (57.2); 2.3395 (0.4); 2.3351 (0.7); 2.3306 (1.0); 2.3260 (0.7); 2.0762 (0.8); 2.0637 (1.7); 2.0552 (1.9); 2.0428 (3.5); 2.0304 (2.0); 2.0220 (1.9); 2.0094 (0.9); 1.9271 (0.7); 1.9121 (6.2); 1.9032 (7.0); 1.8958 (16.0); 1.8883 (7.0); 1.8794 (5.7); 512.1 [M + H].sup.+ 1.8650 (0.7); 1.6102 (15.9); 1.5927 (15.8); 1.0537 (1.7); 1.0427 (5.7); 1.0372 (6.2); 1.0267 (2.7); 1.0218 (5.9); 1.0162 (5.9); 1.0062 (2.0); 0.8049 (2.4); 0.7946 (5.9); 0.7921 (5.4); 0.7892 (5.6); 0.7823 (5.9); 0.7778 (5.8); 0.7662 (2.0); 0.1460 (0.4); 0.0081 (3.4); −0.0001 (107.6); −0.0084 (3.9); −0.1495 (0.4) I-231 [00420] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5127 (1.2); 9.4951 (1.3); 8.9797 (16.0); 8.4157 (1.8); 8.4121 (3.2); 8.4085 (1.8); 8.1439 (1.8); 8.1416 (1.6); 8.0513 (1.8); 6.3408 (0.4); 6.3287 (1.2); 6.3160 (1.2); 6.3035 (0.3); 6.0176 (0.9); 6.0003 (1.5); 5.9827 (0.9); 3.3289 (59.4); 3.0499 (0.6); 3.0421 (0.6); 3.0374 (0.4); 3.0304 (1.2); 3.0221 (0.4); 3.0183 (0.6); 3.0106 (0.6); 2.7502 (6.3); 2.7377 (6.2); 2.6722 (0.4); 2.5256 (1.4); 2.5209 (2.2); 2.5123 (23.2); 2.5078 (45.2); 2.5032 (58.5); 2.4986 (42.3); 2.4941 (20.2); 2.3300 (0.4); 1.6095 (4.9); 1.5921 (4.8); 1.2208 (0.8); 1.2071 (1.4); 1.1992 (1.6); 1.1879 (1.0); 1.1772 (0.4); 1.1303 (0.4); 1.1158 (1.7); 1.1104 (1.4); 1.0962 (1.6); 1.0909 (1.1); 1.0887 (1.2); 0.0079 (2.0); −0.0002 (53.6); −0.0086 (1.7) 546.0 [M + H].sup.+ I-232 [00421] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5329 (0.6); 9.5148 (0.6); 8.4722 (2.5); 8.3110 (1.1); 7.8256 (1.0); 7.8045 (0.8); 6.1366 (0.5); 6.1189 (0.8); 6.1012 (0.5); 3.3279 (53.9); 2.9554 (16.0); 2.8901 (0.5); 2.6721 (0.4); 2.5256 (1.2); 2.5208 (1.9); 2.5122 (22.5); 2.5077 (45.2); 2.5031 (59.4); 2.4985 (43.2); 2.4940 (21.0); 2.3299 (0.4); 1.6413 (2.8); 1.6240 (2.8); 1.1439 (0.4); 1.0399 (0.4); 0.0080 (1.4); −0.0002 (40.2); −0.0085 (1.2) 558.5 [M + H].sup.+ I-233 [00422] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5359 (0.8); 9.5180 (0.8); 8.6045 (0.8); 8.4913 (2.7); 8.3099 (1.2); 8.1432 (0.4); 8.1390 (0.4); 8.1224 (0.5); 8.1179 (0.5); 7.8081 (1.4); 7.7868 (1.3); 6.1680 (0.5); 6.1504 (0.8); 6.1327 (0.5); 3.3272 (52.8); 2.9922 (2.1); 2.9575 (16.0); 2.6719 (0.4); 2.5252 (1.5); 2.5117 (25.8); 2.5074 (50.5); 2.5028 (65.6); 2.4983 (48.1); 2.4939 (23.7); 2.3297 (0.4); 1.6395 (3.0); 1.6221 (3.0); 0.5112 (0.4); 0.4034 (0.5); 0.0079 (1.4); −0.0002 (39.6); −0.0085 (1.5) 570.2 [M + H].sup.+ I-234 [00423] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5350 (0.8); 9.5173 (0.8); 8.4779 (3.1); 8.3104 (1.3); 8.0325 (0.4); 7.8288 (1.4); 7.8065 (1.2); 6.1428 (0.4); 6.1250 (0.7); 6.1076 (0.4); 3.3291 (139.5); 3.0626 (0.7); 2.9559 (16.0); 2.6762 (0.6); 2.6716 (0.8); 2.6672 (0.6); 2.5250 (3.0); 2.5114 (47.9); 2.5072 (90.9); 2.5027 (115.9); 2.4981 (85.0); 2.4938 (42.2); 2.3341 (0.5); 2.3295 (0.7); 2.3250 (0.5); 1.6413 (2.9); 1.6239 (2.8); 0.1459 (0.3); 0.0079 (3.3); −0.0002 (73.2); −0.0085 (3.1) 584.2 [M + H].sup.+ I-235 [00424] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5263 (0.8); 9.5082 (0.8); 8.5962 (1.3); 8.5917 (1.4); 8.4623 (2.7); 8.3148 (1.9); 8.1502 (0.9); 8.1445 (0.8); 8.1290 (1.0); 8.1232 (1.0); 7.8235 (1.3); 7.8023 (1.2); 6.1376 (0.6); 6.1202 (0.9); 6.1027 (0.5); 3.4933 (0.8); 3.4771 (1.4); 3.4595 (0.8); 3.3872 (0.6); 3.3710 (1.2); 3.3610 (1.4); 3.3260 (314.8); 2.9564 (16.0); 2.6900 (3.8); 2.6757 (1.8); 2.6711 (2.4); 2.6667 (1.8); 2.6621 (0.9); 2.5245 (9.4); 2.5111 (149.1); 2.5067 (289.2); 2.5021 (373.0); 2.4976 (272.7); 2.4931 (134.6); 2.3381 (0.8); 2.3335 (1.7); 2.3290 (2.4); 2.3243 (1.7); 1.8894 (0.6); 1.8712 (0.9); 1.8554 (0.8); 1.8396 (0.4); 1.8237 (0.3); 1.8091 (0.8); 1.7925 (0.9); 1.7763 (0.5); 1.6409 (3.0); 1.6235 (3.0); 0.1459 (1.0); 0.0079 (9.6); −0.0002 (258.2); −0.0085 (10.3); −0.1496 (1.1) 570.2 [M + H].sup.+ I-236 [00425] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1331 (0.7); 9.1151 (0.7); 8.9428 (1.3); 8.9413 (1.4); 8.9372 (1.3); 8.9355 (1.3); 8.4664 (1.0); 8.4606 (1.0); 8.4448 (1.1); 8.4390 (1.1); 7.9016 (1.3); 7.9002 (1.3); 7.8801 (1.2); 7.8785 (1.3); 7.4858 (2.0); 7.4822 (1.9); 7.4779 (1.2); 7.2672 (1.2); 7.1051 (0.4); 6.0893 (0.6); 6.0717 (0.9); 6.0542 (0.6); 4.0385 (0.5); 4.0207 (0.5); 3.9074 (0.3); 3.8947 (8.5); 3.3301 (48.9); 2.9641 (16.0); 2.6318 (0.6); 2.5259 (1.0); 2.5211 (1.5); 2.5125 (17.3); 2.5080 (34.3); 2.5034 (44.8); 2.4988 (32.3); 2.4942 (15.5); 2.0505 (0.3); 2.0422 (0.4); 2.0297 (0.6); 2.0172 (0.4); 2.0117 (0.3); 2.0088 (0.4); 1.9895 (2.2); 1.6146 (2.9); 1.5972 (2.9); 1.2313 (1.5); 1.2173 (0.5); 1.2097 (0.4); 1.1994 (0.4); 1.1935 (1.0); 1.1758 (1.8); 1.1581 (0.7); 1.0443 (0.4); 1.0334 (1.1); 1.0279 (1.2); 1.0238 (0.7); 1.0176 (0.6); 1.0126 (1.1); 1.0069 (1.1); 0.9969 (0.4); 0.7883 (0.5); 0.7779 (1.1); 0.7725 (1.1); 0.7655 (1.1); 0.7605 (1.1); 0.7495 (0.4); 0.0080 (1.2); −0.0002 (35.2); −0.0086 (1.2) 519.2 [M + H].sup.+ I-237 [00426] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5431 (0.7); 9.5253 (0.7); 8.9210 (1.2); 8.9194 (1.4); 8.9154 (1.3); 8.9136 (1.3); 8.4560 (2.5); 8.4439 (1.1); 8.4382 (1.0); 8.4224 (1.1); 8.4167 (1.1); 8.3071 (1.1); 7.8906 (1.3); 7.8891 (1.3); 7.8692 (1.2); 7.8676 (1.3); 6.1645 (0.5); 6.1470 (0.9); 6.1294 (0.5); 4.0384 (0.6); 4.0206 (0.6); 3.3305 (36.8); 2.9634 (16.0); 2.6723 (0.4); 2.6679 (0.3); 2.5259 (1.5); 2.5212 (2.3); 2.5125 (25.4); 2.5080 (50.6); 2.5034 (66.0); 2.4988 (47.4); 2.4942 (22.5); 2.3303 (0.4); 1.9895 (2.5); 1.9097 (0.8); 1.6479 (2.9); 1.6305 (2.9); 1.1935 (0.7); 1.1758 (1.4); 1.1580 (0.7); 0.0080 (1.9); 0.0059 (1.0); −0.0002 (51.5); −0.0085 (1.4) 517.0 [M + H].sup.+ I-238 [00427] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5405 (0.7); 9.5224 (0.8); 8.9423 (1.3); 8.9380 (1.3); 8.4684 (1.1); 8.4625 (1.4); 8.4548 (2.7); 8.4470 (1.3); 8.4411 (1.1); 8.3155 (0.9); 8.3093 (1.2); 7.9082 (1.3); 7.8879 (1.2); 7.8866 (1.2); 6.1599 (0.6); 6.1423 (0.9); 6.1247 (0.6); 3.8906 (8.3); 3.3249 (112.0); 2.9656 (16.0); 2.6800 (0.4); 2.6757 (0.9); 2.6712 (1.2); 2.6667 (0.9); 2.5247 (4.5); 2.5199 (7.0); 2.5112 (73.5); 2.5068 (144.4); 2.5023 (187.9); 2.4977 (137.7); 2.4933 (67.9); 2.3337 (0.9); 2.3291 (1.2); 2.3245 (0.8); 1.6462 (3.0); 1.6288 (3.0); 0.1460 (0.6); 0.0080 (5.0); −0.0002 (133.0); −0.0085 (4.8); −0.1496 (0.6) 531.0 [M + H].sup.+ I-239 [00428] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1349 (0.7); 9.1172 (0.8); 8.9197 (1.3); 8.9183 (1.4); 8.9141 (1.3); 8.9126(1.3); 8.4422 (1.0); 8.4365 (1.0); 8.4207 (1.1); 8.4150 (1.1); 7.8832 (1.4); 7.8617 (1.3); 7.8602 (1.2); 7.4867 (2.2); 7.4831 (2.2); 7.2680 (1.2); 6.0927 (0.6); 6.0751 (0.9); 6.0576 (0.6); 3.4233 (4.9); 3.3702 (1.4); 2.9610 (16.0); 2.6762 (0.5); 2.6716 (0.7); 2.6671 (0.5); 2.5251 (2.4); 2.5203 (4.0); 2.5117 (43.9); 2.5073 (84.6); 2.5027 (107.8); 2.4981 (76.5); 2.4935 (35.8); 2.3340 (0.5); 2.3295 (0.6); 2.3250 (0.5); 2.0516 (0.3); 2.0431 (0.4); 2.0307 (0.7); 2.0181 (0.4); 2.0100 (0.4); 1.9890 (0.5); 1.9091 (5.4); 1.6145 (3.0); 1.5971 (2.9); 1.3555 (1.9); 1.2342 (0.6); 1.2168 (0.3); 1.1930 (0.3); 1.1812 (0.5); 1.1753 (0.5); 1.1694 (0.5); 1.0436 (0.4); 1.0328 (1.1); 1.0272 (1.2); 1.0231 (0.6); 1.0170 (0.6); 1.0120 (1.1); 1.0063 (1.1); 0.9963 (0.4); 0.7911 (0.5); 0.7809 (1.2); 0.7753 (1.1); 0.7685 (1.2); 0.7638 (1.1); 0.7524 (0.4); 0.0079 (3.0); 505.1 [M + H].sup.+ −0.0002 (76.8); −0.0086 (2.3) I-240 [00429] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5498 (0.7); 9.5320 (0.7); 8.5247 (1.2); 8.5232 (1.2); 8.5191 (1.3); 8.5175 (1.2); 8.4803 (2.4); 8.3191 (1.1); 8.3147 (1.4); 8.0687 (0.8); 8.0630 (0.8); 8.0475 (1.0); 8.0418 (1.0); 7.8444 (1.3); 7.8430 (1.3); 7.8233 (1.1); 7.8218 (1.1); 6.1401 (0.5); 6.1226 (0.8); 6.1049 (0.5); 3.6250 (0.6); 3.6070 (0.7); 3.3298 (416.1); 2.9525 (15.0); 2.6900 (16.0); 2.6804 (0.7); 2.6759 (1.3); 2.6713 (1.8); 2.6668 (1.3); 2.6625 (0.6); 2.5249 (6.4); 2.5201 (9.6); 2.5114 (103.3); 2.5070 (204.4); 2.5024 (265.1); 2.4978 (191.4); 2.4933 (92.1); 2.3383 (0.5); 2.3338 (1.1); 2.3292 (1.6); 2.3246 (1.1); 2.3204 (0.5); 1.6415 (2.7); 1.6242 (2.7); 0.1460 (0.5); 0.0080 (4.1); −0.0002 (122.4); −0.0085 (3.9); −0.1495 (0.5) 586.4 [M + H].sup.+ I-241 [00430] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2923 (4.4); 9.2748 (4.4); 8.9234 (7.0); 8.9217 (7.5); 8.9179 (7.6); 8.9161 (7.2); 8.4430 (6.0); 8.4373 (5.6); 8.4213 (6.3); 8.4156 (6.4); 8.3149 (4.7); 8.1529 (5.9); 8.1490 (9.9); 8.1452 (6.1); 7.8887 (6.0); 7.8195 (10.4); 7.8162 (6.4); 7.8135 (6.3); 7.7997 (7.0); 7.7980 (7.1); 6.0812 (0.7); 6.0652 (3.1); 6.0478 (4.8); 6.0303 (3.1); 6.0126 (0.9); 5.9867 (11.9); 5.9634 (0.4); 3.5883 (0.3); 3.5773 (0.4); 3.5680 (0.9); 3.5552 (0.4); 3.5298 (0.4); 3.4577 (0.6); 3.4496 (0.6); 3.3284 (3074.9); 3.2674 (0.6); 2.7321 (0.4); 2.7284 (0.4); 2.7076 (0.4); 2.6801 (4.4); 2.6756 (9.2); 2.6711 (13.0); 2.6665 (9.4); 2.6618 (4.6); 2.6400 (0.7); 2.6072 (1.0); 2.5245 (43.4); 2.5198 (64.4); 2.5111 (743.9); 2.5067 (1502.0); 2.5021 (1974.3); 2.4975 (1439.2); 2.4930 (699.3); 2.3900 (0.4); 2.3379 (4.1); 2.3334 (8.9); 2.3289 (12.5); 2.3243 (9.0); 2.3199 (4.2); 1.5834 (16.0); 1.5661 (16.0); 1.2362 (0.4); 497.9 [M + H].sup.+ 0.1458 (4.8); 0.0296 (0.6); 0.0079 (37.3); −0.0003 (1172.9); −0.0086 (39.4); −0.0455 (0.4); −0.1497 (4.7) I-242 [00431] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4851 (1.4); 9.4672 (1.5); 8.8534 (8.8); 8.8413 (9.1); 8.4558 (2.0); 8.4521 (3.6); 8.4485 (2.1); 8.1701 (2.1); 8.1007 (1.9); 8.0982 (2.1); 8.0958 (1.9); 8.0925 (1.5); 8.0855 (5.1); 8.0805 (1.6); 8.0687 (1.6); 8.0636 (5.9); 8.0571 (0.7); 7.7697 (0.6); 7.7631 (5.8); 7.7581 (1.6); 7.7462 (1.5); 7.7412 (5.1); 7.7348 (0.5); 7.4349 (2.3); 7.4228 (4.3); 7.4107 (2.2); 6.0235 (1.1); 6.0061 (1.7); 5.9885 (1.1); 5.7485 (4.2); 3.3650 (0.4); 3.3385 (141.5); 2.6782 (0.4); 2.6736 (0.5); 2.6691 (0.4); 2.5438 (0.7); 2.5270 (1.5); 2.5224 (2.2); 2.5137 (29.9); 2.5092 (60.8); 2.5046 (80.0); 2.4999 (58.0); 2.4954 (28.0); 2.3361 (0.4); 2.3313 (0.5); 2.3266 (0.4); 2.0771 (16.0); 1.6059 (5.7); 1.5886 (5.6) 568.1 [M + H].sup.+ I-243 [00432] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5141 (2.2); 9.4962 (2.3); 8.8597 (15.5); 8.8476 (16.0); 8.4412 (3.3); 8.4368 (5.0); 8.4326 (3.6); 8.3515 (3.2); 8.3476 (5.6); 8.3439 (3.0); 8.1774 (3.2); 8.1730 (5.2); 8.1685 (2.8); 7.5428 (1.9); 7.4454 (4.0); 7.4333 (7.4); 7.4212 (4.1); 7.4128 (4.7); 7.2830 (2.4); 6.0375 (1.7); 6.0200 (2.7); 6.0025 (1.7); 5.9852 (0.3); 5.7557 (6.6); 3.3327 (154.9); 2.6765 (0.6); 2.6719 (0.8); 2.6673 (0.6); 2.5422 (0.7); 2.5254 (2.5); 2.5208 (3.7); 2.5120 (47.8); 2.5075 (96.6); 2.5029 (126.8); 2.4982 (91.2); 2.4937 (43.2); 2.3343 (0.6); 2.3297 (0.8); 2.3250 (0.6); 2.0758 (3.0); 1.6034 (9.1); 1.5861 (9.1); 458.0 [M + H].sup.+ −0.0002 (0.4) I-244 [00433] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5706 (0.6); 9.5529 (0.6); 8.8570 (4.4); 8.8449 (4.5); 8.5252 (0.9); 8.5211 (1.4); 8.5166 (1.1); 8.4656 (1.3); 8.4080 (0.8); 8.4034 (1.3); 8.3731 (0.5); 7.4433 (1.1); 7.4312 (2.1); 7.4191 (1.1); 6.0419 (0.5); 6.0243 (0.8); 6.0067 (0.5); 5.7579 (1.8); 3.3305 (390.3); 2.6800 (0.9); 2.6754 (1.9); 2.6708 (2.6); 2.6662 (1.9); 2.6617 (0.9); 2.5412 (3.7); 2.5244 (8.8); 2.5197 (12.8); 2.5110 (157.3); 2.5065 (318.9); 2.5018 (418.0); 2.4972 (299.7); 2.4926 (141.7); 2.3379 (0.8); 2.3332 (1.8); 2.3287 (2.6); 2.3241 (1.8); 2.3195 (0.8); 2.0747 (16.0); 1.6078 (2.6); 1.5905 (2.6); 1.2726 (0.8); 1.2576 476.0 [M + H].sup.+ (1.4); 1.2421 (1.2); −0.0002 (1.3) I-245 [00434] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4247 (3.2); 9.4068 (3.2); 8.8537 (15.6); 8.8416 (16.0); 8.2497 (5.9); 8.0302 (5.6); 7.9885 (3.9); 7.9849 (6.4); 7.4393 (4.1); 7.4272 (7.7); 7.4152 (4.0); 6.0474 (0.4); 6.0302 (2.2); 6.0127 (3.5); 5.9951 (2.2); 5.9777 (0.5); 5.7443 (9.4); 3.3343 (144.2); 2.6770 (0.7); 2.6725 (1.0); 2.6680 (0.7); 2.6633 (0.3); 2.5430 (1.7); 2.5259 (2.9); 2.5209 (4.2); 2.5123 (57.3); 2.5080 (116.6); 2.5035 (154.5); 2.4990 (114.3); 2.4945 (57.0); 2.3388 (0.3); 2.3348 (0.7); 2.3303 (1.0); 2.3259 (0.7); 2.3214 (0.4); 2.2899 (0.6); 2.2772 (1.4); 2.2687 (1.4); 2.2564 (2.7); 2.2440 (1.6); 2.2355 (1.4); 2.2229 (0.7); 2.0765 (3.4); 1.6082 (12.1); 1.5909 (12.1); 1.1355 (1.5); 1.1245 (3.6); 1.1192 482.0 [M + H].sup.+ (4.0); 1.1089 (2.5); 1.1039 (3.8); 1.0983 (3.9); 1.0882 (1.9); 0.8935 (1.8); 0.8828 (4.3); 0.8791 (4.2); 0.8709 (4.0); 0.8662 (4.3); 0.8547 (1.4); 0.0001 (0.3) I-246 [00435] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5096 (2.5); 9.4924 (2.5); 8.9307 (4.4); 8.9290 (4.6); 8.9252 (4.6); 8.9234 (4.4); 8.4475 (3.8); 8.4419 (3.6); 8.4283 (4.0); 8.4254 (9.1); 8.4205 (6.4); 8.1733 (3.6); 8.0344 (3.6); 7.8273 (4.5); 7.8258 (4.4); 7.8057 (4.3); 7.8040 (4.3); 6.1285 (0.4); 6.1117 (1.8); 6.0944 (2.9); 6.0770 (1.8); 6.0598 (0.4); 5.9981 (6.8); 3.4840 (1.9); 3.4656 (6.5); 3.4472 (6.6); 3.4289 (2.1); 3.3319 (495.8); 3.2911 (0.4); 2.6801 (1.2); 2.6756 (2.5); 2.6711 (3.4); 2.6666 (2.5); 2.6620 (1.1); 2.5724 (0.4); 2.5415 (11.1); 2.5246 (11.2); 2.5199 (16.6); 2.5112 (207.3); 2.5067 (417.1); 2.5021 (544.6); 2.4975 (391.4); 2.4929 (185.9); 2.3380 (1.1); 2.3335 (2.4); 2.3289 (3.3); 2.3244 (2.4); 2.3198 (1.1); 2.0748 (10.9); 1.6131 (9.5); 1.5958 (9.4); 1.1465 (6.8); 1.1282 (16.0); 1.1098 (6.7): −0.0002 (1.1) 510.1 [M + H].sup.+ I-247 [00436] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5156 (1.6); 9.4982 (1.7); 8.9152 (2.8); 8.9111 (2.9); 8.4896 (2.1); 8.4860 (3.8); 8.4824 (2.2); 8.4439 (2.2); 8.4383 (2.1); 8.4222 (2.2); 8.4166 (2.3); 8.1823 (2.4); 8.1333 (2.3); 8.0950 (0.6); 8.0885 (5.2); 8.0837 (1.7); 8.0717 (1.8); 8.0668 (6.0); 8.0605 (0.7); 7.8222 (2.9); 7.8020 (2.7); 7.8005 (2.7); 7.7693 (0.7); 7.7625 (6.0); 7.7576 (1.8); 7.7456 (1.7); 7.7407 (5.2); 6.0869 (1.2); 6.0694 (1.8); 6.0524 (1.1); 6.0355 (0.4); 5.9893 (4.4); 3.4663 (0.4); 3.3320 (1150.1); 2.8903 (0.5); 2.7311 (0.5); 2.6800 (2.1); 2.6755 (4.3); 2.6709 (5.9); 2.6664 (4.3); 2.6620 (2.0); 2.5413 (13.9); 2.5244 (19.5); 2.5196 (30.8); 2.5110 (361.5); 2.5065 (709.4); 2.5020 (918.6); 2.4974 (665.1); 2.4929 (319.8); 2.3377 (1.9); 2.3333 (4.1); 2.3288 (5.6); 2.3242 (4.0); 2.3197 (1.8); 2.0748 (16.0); 1.6047 (5.9); 1.5873 (5.9); −0.0002 (1.6) 592.0 [M + H].sup.+ I-248 [00437] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5500 (3.3); 9.5328 (3.4); 8.9280 (5.7); 8.9264 (6.2); 8.9225 (6.2); 8.9208 (5.9); 8.4826 (4.7); 8.4783 (7.3); 8.4740 (5.0); 8.4472 (5.1); 8.4416 (4.8); 8.4255 (5.3); 8.4199 (5.4); 8.3862 (4.6); 8.3824 (8.0); 8.3787 (4.3); 8.1910 (4.5); 8.1866 (7.5); 8.1822 (4.0); 7.8270 (6.2); 7.8253 (6.1); 7.8053 (6.0); 7.8036 (5.9); 7.5490 (2.7); 7.4190 (6.4); 7.2892 (3.3); 6.1194 (0.5); 6.1022 (2.5); 6.0850 (3.9); 6.0676 (2.5); 6.0502 (0.6); 6.0003 (9.0); 3.3339 (451.2); 2.6806 (0.8); 2.6761 (1.8); 2.6715 (2.4); 2.6669 (1.7); 2.6625 (0.8); 2.5419 (12.4); 2.5250 (7.8); 2.5203 (11.5); 2.5116 (147.0); 2.5071 (297.3); 2.5025 (388.6); 2.4979 (278.8); 2.4933 (132.5); 2.3385 (0.8); 2.3339 (1.7); 2.3293 (2.4); 2.3248 (1.7); 2.3202 (0.8); 2.0752 (16.0); 1.6034 (12.9); 1.5861 (12.9); −0.0001 (0.8) 582.0 [M + H].sup.+ I-249 [00438] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6024 (4.1); 9.5852 (4.2); 8.9236 (7.3); 8.9218 (8.0); 8.9181 (7.8); 8.9162 (7.6); 8.5620 (6.0); 8.5576 (9.1); 8.5534 (6.9); 8.4993 (8.1); 8.4469 (6.7); 8.4413 (6.3); 8.4253 (7.6); 8.4197 (11.2); 8.4166 (7.8); 7.8262 (7.7); 7.8244 (7.9); 7.8046 (7.4); 7.8027 (7.7); 6.1237 (0.6); 6.1067 (3.1); 6.0894 (4.9); 6.0721 (3.1); 6.0545 (0.6); 6.0050 (11.0); 3.3334 (688.1); 2.6805 (1.2); 2.6760 (2.6); 2.6714 (3.6); 2.6668 (2.6); 2.6623 (1.2); 2.5418 (17.5); 2.5250 (11.9); 2.5203 (17.2); 2.5116 (215.9); 2.5071 (437.1); 2.5025 (572.7); 2.4978 (410.3); 2.4932 (193.4); 2.3384 (1.1); 2.3339 (2.5); 2.3293 (3.5); 2.3247 (2.5); 2.3202 (1.1); 2.0751 (11.8); 1.6092 (16.0); 1.5918 (15.9); −0.0002 (1.2) 500.0 [M + H].sup.+ I-250 [00439] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4590 (4.2); 9.4417 (4.3); 8.9177 (7.6); 8.9158 (8.1); 8.9121 (8.2); 8.9102 (7.9); 8.4450 (6.8); 8.4394 (6.5); 8.4234 (7.2); 8.4177 (7.3); 8.2884 (7.8); 8.0404 (7.6); 8.0365 (6.2); 8.0327 (7.5); 8.0286 (8.9); 8.0247 (3.6); 7.8228 (7.8); 7.8210 (7.9); 7.8012 (7.5); 7.7993 (7.8); 6.1125 (0.6); 6.0955 (3.1); 6.0782 (4.9); 6.0608 (3.1); 6.0436 (0.7); 5.9878 (11.4); 3.3340 (474.0); 2.6808 (0.8); 2.6762 (1.9); 2.6717 (2.7); 2.6670 (1.9); 2.6625 (0.9); 2.5420 (14.3); 2.5252 (8.5); 2.5205 (12.3); 2.5118 (157.5); 2.5073 (323.6); 2.5027 (428.4); 2.4980 (310.2); 2.4934 (148.5); 2.3386 (0.9); 2.3341 (1.9); 2.3294 (2.7); 2.3249 (1.9); 2.3203 (0.9); 2.2998 (0.8); 2.2873 (1.8); 2.2789 (1.9); 2.2755 (1.4); 2.2665 (3.5); 2.2540 (2.0); 2.2456 (1.9); 2.2331 (1.0); 2.0752 (15.3); 1.6096 (16.0); 1.5922 (16.0); 1.1432 (2.0); 1.1316 (5.3); 1.1262 (5.9); 1.1153 (3.2); 1.1107 (5.5); 1.1052 (5.8); 1.0946 (2.4); 0.9030 (2.6); 0.8918 506.0 [M + H].sup.+ (6.5); 0.8869 (6.4); 0.8797 (5.9); 0.8747 (7.3); 0.8628 (2.0); −0.0003 (0.9) I-251 [00440] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4971 (4.0); 9.4799 (4.1); 8.9370 (7.0); 8.9354 (7.2); 8.9315 (7.3); 8.9298 (6.8); 8.4779 (5.6); 8.4743 (10.0); 8.4707 (5.6); 8.4490 (5.9); 8.4434 (5.5); 8.4273 (6.2); 8.4217 (6.1); 8.1511 (5.6); 8.0820 (5.7); 7.8284 (7.2); 7.8268 (7.0); 7.8068 (6.8); 7.8051 (6.8); 6.1315 (0.6); 6.1148 (2.8); 6.0975 (4.5); 6.0801 (2.9); 6.0626 (0.6); 5.9971 (10.7); 3.3639 (48.2); 3.3311 (864.6); 2.6801 (1.6); 2.6756 (3.4); 2.6711 (4.7); 2.6665 (3.3); 2.6620 (1.6); 2.5414 (13.3); 2.5246 (15.7); 2.5198 (24.3); 2.5112 (288.2); 2.5067 (570.1); 2.5021 (739.3); 2.4975 (530.0); 2.4929 (251.2); 2.3381 (1.5); 2.3335 (3.3); 2.3289 (4.6); 2.3244 (3.2); 2.3198 (1.5); 2.0750 (16.0); 1.6124 (14.9); 1.5951 (14.9); −0.0001 (1.5) 496.1 [M + H].sup.+ I-252 [00441] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1019 (0.7); 9.0841 (0.7); 8.5820 (1.2); 8.5805 (1.3); 8.5763 (1.3); 8.5748 (1.2); 8.3157 (0.5); 8.1415 (1.0); 8.1358 (0.9); 8.1203 (1.1); 8.1145 (1.0); 7.8084 (1.3); 7.8071 (1.3); 7.7873 (1.2); 7.7858 (1.2); 7.4727 (2.1); 7.4692 (2.1); 7.2679 (1.0); 6.0565 (0.5); 6.0388 (0.8); 6.0211 (0.5); 3.4922 (0.7); 3.4755 (1.4); 3.4583 (0.8); 3.3691 (0.5); 3.3523 (1.4); 3.3297 (173.8); 2.9551 (16.0); 2.6899 (2.3); 2.6804 (0.4); 2.6760 (0.8); 2.6714 (1.1); 2.6668 (0.8); 2.6625 (0.4); 2.5250 (3.7); 2.5202 (5.4); 2.5115 (62.5); 2.5070 (126.4); 2.5024 (167.0); 2.4978 (122.1); 2.4933 (58.9); 2.3384 (0.3); 2.3338 (0.8); 2.3292 (1.1); 2.3247 (0.8); 2.3201 (0.4); 2.0388 (0.3); 2.0259 (0.6); 2.0134 (0.4); 2.0050 (0.3); 1.8871 (0.5); 1.8707 (0.8); 1.8533 (0.7); 1.8380 (0.3); 1.8067 (0.7); 1.7911 (0.8); 1.7745 (0.4); 1.6072 (2.9); 1.5898 (2.8); 1.0319 (0.9); 1.0264 (1.0); 1.0191 (0.5); 1.0161 (0.4); 1.0111 (1.0); 1.0054 (1.0); 0.7824 (0.5); 0.7699 (1.0); 0.7651 (0.9); 0.7587 (1.0); 0.7536 (0.7); 0.7461 (0.4); 0.1460 (0.4); 0.0079 (2.8); 558.2 [M + H].sup.+ −0.0002 (91.1); −0.0086 (2.9); −0.1496 (0.4) I-253 [00442] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1212 (0.7); 9.1030 (0.8); 8.5037 (1.3); 8.5024 (1.3); 8.4982 (1.3); 8.0616 (0.9); 8.0560 (0.8); 8.0405 (1.1); 8.0348 (1.1); 7.8305 (1.4); 7.8094 (1.2); 7.8079 (1.2); 7.4889 (1.1); 7.4862 (1.1); 7.4804 (1.4); 7.4767 (1.7); 7.2783 (1.1); 6.0578 (0.5); 6.0401 (0.9); 6.0225 (0.6); 3.6532 (0.4); 3.6106 (0.6); 3.6012 (0.5); 3.5694 (0.5); 3.3305 (124.4); 2.9525 (16.0); 2.6761 (0.6); 2.6714 (0.8); 2.6668 (0.6); 2.5250 (2.8); 2.5203 (4.1); 2.5115 (46.8); 2.5071 (94.2); 2.5025 (123.8); 2.4979 (90.5); 2.4933 (43.9); 2.3339 (0.6); 2.3293 (0.8); 2.3247 (0.6); 2.0748 (3.5); 2.0445 (0.3); 2.0322 (0.6); 2.0197 (0.4); 2.0113 (0.4); 1.6075 (2.9); 1.5901 (2.9); 1.0348 (0.9); 1.0294 (1.0); 1.0266 (0.8); 1.0138 (0.9); 1.0085 (1.0); 0.7847 (0.7); 0.7725 (0.9); 0.7685 (0.9); 0.7652 (0.9); 0.7537 (0.6); 0.0080 (1.7); −0.0002 (55.8); −0.0085 (1.8) 574.2 [M + H].sup.+ I-254 [00443] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1247 (0.6); 9.1060 (0.6); 8.4785 (0.6); 8.3161 (0.4); 8.0266 (0.3); 7.8184 (1.4); 7.7974 (1.1); 7.4979 (1.9); 7.2687 (1.1); 6.0657 (0.4); 6.0481 (0.5); 6.0301 (0.4); 3.3299 (152.3); 3.0652 (0.6); 2.9528 (16.0); 2.6805 (0.3); 2.6760 (0.7); 2.6714 (1.0); 2.6668 (0.7); 2.6624 (0.3); 2.5249 (3.6); 2.5202 (5.5); 2.5115 (60.8); 2.5070 (119.8); 2.5024 (155.2); 2.4978 (112.1); 2.4933 (53.7); 2.3384 (0.3); 2.3338 (0.7); 2.3293 (1.0); 2.3246 (0.7); 2.0438 (0.3); 2.0316 (0.6); 2.0190 (0.4); 2.0109 (0.4); 1.6073 (2.8); 1.5899 (2.8); 1.0445 (0.4); 1.0341 (1.1); 1.0284 (1.2); 1.0184 (0.6); 1.0132 (1.1); 1.0075 (1.1); 0.9977 (0.5); 0.7931 (0.4); 0.7830 (1.0); 0.7800 (1.0); 0.7708 (1.0); 0.7669 (1.0); 0.7553 (0.4); 0.0080 (2.3); −0.0002 (72.0); −0.0085 (2.4) 572.3 [M + H].sup.+ I-255 [00444] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1248 (0.8); 9.1069 (0.8); 8.6009 (0.8); 8.3163 (0.5); 8.1354 (0.4); 8.1180 (0.5); 7.7990 (1.4); 7.7775 (1.2); 7.5149 (2.5); 7.2675 (1.2); 6.0919 (0.5); 6.0744 (0.7); 6.0566 (0.5); 3.3288 (215.0); 2.9928 (2.0); 2.9539 (16.0); 2.6756 (1.3); 2.6711 (1.7); 2.6668 (1.2); 2.6017 (0.4); 2.5244 (7.3); 2.5109 (102.7); 2.5067 (194.7); 2.5022 (250.6); 2.4977 (186.4); 2.4936 (94.8); 2.3335 (1.2); 2.3290 (1.6); 2.3246 (1.2); 2.0747 (0.3); 2.0435 (0.4); 2.0311 (0.7); 2.0187 (0.4); 2.0106 (0.4); 1.6045 (3.0); 1.5871 (2.9); 1.0444 (0.4); 1.0331 (1.1); 1.0277 (1.2); 1.0170 (0.7); 1.0122 (1.2); 1.0067 (1.1); 0.9965 (0.5); 0.7940 (0.5); 0.7833 (1.3); 0.7780 (1.3); 0.7712 (1.2); 0.7660 (1.4); 0.7545 (0.4); 0.5161 (0.4); 0.4077 (0.5); 0.1458 (0.4); 0.0078 (4.0); −0.0002 (96.3); −0.0084 (4.0); −0.1495 (0.5) 558.2 [M + H].sup.+ I-256 [00445] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1224 (0.7); 9.1043 (0.8); 8.5019 (1.3); 8.4977 (1.3); 8.3160 (0.7); 8.0562 (0.9); 8.0505 (0.9); 8.0350 (1.1); 8.0293 (1.0); 7.8138 (1.3); 7.7928 (1.1); 7.4942 (2.3); 7.4902 (2.5); 7.2668 (1.1); 6.0608 (0.5); 6.0431 (0.8); 6.0255 (0.6); 3.3291 (254.2); 3.0019 (1.7); 2.9516 (16.0); 2.9083 (1.8); 2.8671 (0.5); 2.6802 (0.7); 2.6758 (1.4); 2.6713 (2.0); 2.6667 (1.4); 2.6623 (0.7); 2.5971 (0.4); 2.5247 (7.1); 2.5200 (10.7); 2.5113 (114.0); 2.5068 (225.2); 2.5023 (293.4); 2.4977 (213.5); 2.4932 (103.2); 2.3382 (0.6); 2.3336 (1.4); 2.3291 (1.9); 2.3246 (1.3); 2.3202 (0.6); 2.0746 (0.4); 2.0504 (0.3); 2.0416 (0.3); 2.0294 (0.6); 2.0169 (0.4); 2.0088 (0.4); 1.6077 (2.9); 1.5903 (2.8); 1.0437 (0.4); 1.0334 (1.0); 1.0279 (1.0); 1.0180 (0.5); 1.0127 (1.0); 1.0068 (1.0); 0.9974 (0.4); 0.7903 (0.5); 0.7804 (1.0); 0.7769 (1.0); 0.7682 (1.0); 0.7642 (0.9); 0.7527 (0.4); 0.1459 (0.5); 0.0080 (4.4); −0.0002 (128.0); −0.0085 (4.1); −0.1496 (0.5) 532.2 [M + H].sup.+ I-257 [00446] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1059 (0.7); 9.0877 (0.7); 8.4771 (1.2); 8.4756 (1.2); 8.4715 (1.3); 8.4698 (1.2); 8.3161 (1.0); 8.0459 (0.9); 8.0402 (0.8); 8.0248 (1.1); 8.0190 (1.0); 7.8318 (1.4); 7.8304 (1.4); 7.8107 (1.2); 7.8091 (1.2); 7.4676 (1.0); 7.4651 (1.0); 7.4580 (1.2); 7.4542 (1.6); 7.2709 (1.0); 6.0558 (0.5); 6.0380 (0.8); 6.0205 (0.5); 3.3312 (395.3); 2.9553 (16.0); 2.6803 (0.9); 2.6758 (2.0); 2.6712 (2.7); 2.6666 (1.9); 2.6621 (0.9); 2.6004 (0.4); 2.5248 (9.2); 2.5201 (13.2); 2.5114 (152.9); 2.5068 (309.6); 2.5022 (407.3); 2.4976 (294.7); 2.4930 (140.5); 2.3382 (0.8); 2.3336 (1.8); 2.3291 (2.6); 2.3245 (1.8); 2.3200 (0.8); 2.0252 (0.6); 2.0123 (0.3); 2.0041 (0.3); 1.6059 (2.8); 1.5886 (2.8); 1.1431 (0.5); 1.0438 (0.4); 1.0322 (1.2); 1.0270 (1.4); 1.0114 (1.4); 1.0060 (1.4); 0.9952 (0.7); 0.7783 (0.7); 0.7660 (0.9); 0.7622 (0.9); 0.7582 (0.8); 0.7470 (0.5); 0.1460 (0.8); 0.0080 (6.2); −0.0002 (206.5); −0.0085 (6.4); −0.1496 (0.8) 602.3 [M + H].sup.+ I-258 [00447] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5136 (0.8); 9.4957 (0.8); 8.9260 (1.3); 8.9245 (1.4); 8.9204 (1.4); 8.9188 (1.4); 8.4489 (1.1); 8.4432 (1.0); 8.4323 (1.2); 8.4282 (2.6); 8.4218 (1.3); 8.0985 (1.1); 8.0962 (1.1); 8.0714 (1.2); 8.0699 (1.2); 7.8955 (1.4); 7.8942 (1.4); 7.8741 (1.3); 7.8727 (1.3); 6.1630 (0.6); 6.1454 (0.9); 6.1278 (0.6); 4.0379 (0.4); 4.0201 (0.4); 3.3867 (0.7); 3.3508 (10.6); 3.3345 (37.8); 2.9666 (16.0); 2.6763 (0.5); 2.6718 (0.7); 2.6672 (0.5); 2.6108 (0.3); 2.5252 (2.5); 2.5204 (4.0); 2.5118 (39.4); 2.5074 (77.6); 2.5028 (101.2); 2.4981 (73.6); 2.4936 (35.4); 2.3342 (0.4); 2.3296 (0.6); 2.3250 (0.5); 1.9891 (1.9); 1.9091 (1.7); 1.6411 (3.0); 1.6236 (2.9); 1.3553 (0.4); 1.1932 (0.6); 1.1754 (1.1); 1.1693 (0.4); 1.1576 (0.5); 0.0080 (1.2); −0.0002 (33.5); −0.0086 (0.9) 543.0 [M + H].sup.+ I-259 [00448] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5073 (1.0); 9.4898 (1.0); 8.9477 (1.6); 8.9422 (1.7); 8.4713 (0.9); 8.4659 (0.8); 8.4498 (1.0); 8.4459 (0.9); 8.4180 (2.0); 8.0943 (1.6); 8.0701 (1.7); 7.9114 (1.7); 7.8898 (1.6); 6.1551 (0.6); 6.1378 (1.0); 6.1201 (0.6); 3.9052 (0.5); 3.8922 (8.2); 3.3480 (9.1); 3.3253 (60.3); 2.9679 (16.0); 2.6707 (0.6); 2.6114 (0.4); 2.5010 (88.2); 2.3279 (0.6); 1.9873 (0.3); 1.6395 (3.5); 1.6221 (3.4); 0.1658 (0.4); −0.0005 (30.9); −0.0022 (32.9) 557.0 [M + H].sup.+ I-260 [00449] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1140 (0.6); 9.0957 (0.6); 8.3158 (0.5); 7.8123 (1.0); 7.7913 (0.9); 7.4848 (1.9); 7.2664 (1.1); 6.0572 (0.5); 6.0396 (0.8); 6.0219 (0.5); 3.3267 (92.6); 2.9528 (16.0); 2.8765 (0.6); 2.6802 (0.4); 2.6757 (0.9); 2.6712 (1.2); 2.6666 (0.9); 2.6622 (0.4); 2.5247 (4.4); 2.5199 (6.8); 2.5113 (69.8); 2.5068 (138.5); 2.5022 (181.0); 2.4976 (131.6); 2.4931 (63.4); 2.3383 (0.4); 2.3337 (0.8); 2.3290 (1.1); 2.3245 (0.8); 2.3200 (0.4); 2.0408 (0.3); 2.0284 (0.6); 2.0160 (0.4); 2.0075 (0.3); 1.6064 (2.8); 1.5890 (2.8); 1.1428 (0.4); 1.1289 (0.3); 1.0425 (0.7); 1.0326 (1.3); 1.0270 (1.3); 1.0117 (1.1); 1.0060 (1.1); 0.9966 (0.4); 0.7870 (0.4); 0.7753 (1.0); 0.7698 (1.0); 0.7637 (1.0); 0.7587 (0.6); 0.7513 (0.4); 0.0080 (1.5); −0.0002 (42.3); −0.0085 (1.3) 546.2 [M + H].sup.+ I-261 [00450] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5493 (0.7); 9.5315 (0.7); 8.5153 (1.4); 8.5110 (1.4); 8.4758 (2.1); 8.3161 (1.4); 8.0568 (0.9); 8.0511 (0.8); 8.0356 (1.1); 8.0299 (1.1); 7.8418 (1.4); 7.8210 (1.2); 7.8197 (1.2); 6.1488 (0.5); 6.1313 (0.9); 6.1136 (0.6); 3.5930 (0.3); 3.5870 (0.4); 3.5775 (0.5); 3.5711 (0.6); 3.5667 (0.6); 3.5603 (0.5); 3.5510 (0.5); 3.5447 (0.4); 3.3533 (0.4); 3.3304 (99.2); 3.3115 (0.3); 2.9537 (16.0); 2.6765 (0.4); 2.6719 (0.6); 2.6673 (0.4); 2.5254 (2.1); 2.5206 (3.0); 2.5120 (34.6); 2.5075 (69.0); 2.5029 (90.4); 2.4983 (65.7); 2.4938 (31.8); 2.3343 (0.4); 2.3298 (0.6); 2.3252 (0.4); 2.0750 (3.8); 1.6421 (3.0); 1.6247 (3.0); 1.1446 (0.5); 0.9877 (0.5); 0.0080 (0.6); −0.0002 (19.4); −0.0085 (0.6) 614.5 [M + H].sup.+ I-262 [00451] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4927 (0.6); 9.4747 (0.6); 8.4169 (1.4); 8.1062 (0.9); 8.0679 (1.0); 7.8237 (1.0); 7.8024 (0.8); 6.1225 (0.5); 6.1048 (0.8); 6.0871 (0.5); 3.3498 (8.5); 3.3313 (83.3); 2.9584 (16.0); 2.8955 (0.6); 2.6763 (0.3); 2.6717 (0.5); 2.6671 (0.3); 2.5253 (1.5); 2.5206 (2.3); 2.5119 (27.6); 2.5073 (55.2); 2.5027 (71.8); 2.4981 (51.4); 2.4935 (24.3); 2.3342 (0.3); 2.3296 (0.4); 2.0749 (0.7); 1.6351 (2.7); 1.6176 (2.6); 1.1444 (0.4); 1.0498 (0.4); 0.0080 (0.6); −0.0002 (19.7); −0.0086 (0.6) 584.2 [M + H].sup.+ I-263 [00452] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4863 (0.8); 9.4682 (0.8); 8.5973 (1.4); 8.5931 (1.4); 8.4136 (1.1); 8.4100 (1.9); 8.4065 (1.1); 8.3157 (0.6); 8.1503 (0.9); 8.1446 (0.9); 8.1291 (1.1); 8.1233 (1.0); 8.0958 (1.2); 8.0698 (1.2); 7.8217 (1.4); 7.8006 (1.2); 6.1258 (0.6); 6.1080 (0.9); 6.0904 (0.6); 3.4945 (0.8); 3.4778 (1.5); 3.4611 (0.9); 3.4000 (0.6); 3.3927 (0.7); 3.3837 (1.1); 3.3773 (1.2); 3.3679 (0.9); 3.3605 (1.2); 3.3485 (10.0); 3.3289 (261.0); 2.9597 (16.0); 2.6897 (0.9); 2.6758 (1.3); 2.6712 (1.8); 2.6668 (1.3); 2.6622 (0.6); 2.6053 (0.5); 2.5246 (6.9); 2.5198 (11.0); 2.5112 (106.8); 2.5068 (207.0); 2.5023 (267.5); 2.4977 (195.8); 2.4932 (96.5); 2.3383 (0.6); 2.3336 (1.2); 2.3291 (1.7); 2.3245 (1.2); 2.3202 (0.6); 1.8890 (0.5); 1.8723 (0.9); 1.8559 (0.8); 1.8404 (0.5); 1.8190 (0.8); 1.8032 (0.9); 1.7869 (0.5); 1.6353 (3.0); 1.6179 (2.9); 0.0080 (1.6); −0.0002 (42.1); −0.0085 (1.5) 596.2 [M + H].sup.+ I-264 [00453] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5043 (0.9); 9.4866 (0.9); 8.5212 (1.5); 8.5158 (1.6); 8.4168 (2.0); 8.4134 (1.2); 8.3156 (0.5); 8.1103 (1.3); 8.0742 (1.4); 8.0675 (1.4); 8.0615 (0.9); 8.0460 (1.1); 8.0403 (1.1); 7.8409 (1.6); 7.8197 (1.3); 6.1239 (0.6); 6.1064 (0.9); 6.0887 (0.6); 3.6137 (0.9); 3.5237 (0.3); 3.3519 (10.4); 3.3280 (255.3); 2.9567 (16.0); 2.6755 (1.3); 2.6711 (1.8); 2.6667 (1.3); 2.6008 (0.4); 2.5243 (8.2); 2.5065 (211.4); 2.5021 (270.3); 2.4976 (200.2); 2.3332 (1.2); 2.3289 (1.7); 2.3246 (1.2); 1.6361 (3.2); 1.6187 (3.1); 0.0078 (1.5); −0.0003 (37.0); −0.0084 (1.4) 612.2 [M + H].sup.+ I-265 [00454] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5091 (0.9); 9.4916 (0.9); 8.5163 (1.7); 8.5115 (1.6); 8.4227 (1.6); 8.3155 (0.4); 8.1095 (1.3); 8.0733 (1.6); 8.0565 (0.9); 8.0510 (0.8); 8.0354 (1.0); 8.0299 (1.0); 7.8407 (1.6); 7.8196 (1.4); 6.1344 (0.6); 6.1169 (1.0); 6.0995 (0.6); 3.5891 (0.6); 3.5688 (0.9); 3.5528 (0.7); 3.3518 (10.1); 3.3285 (206.6); 2.9567 (16.0); 2.6713 (1.7); 2.6016 (0.4); 2.5064 (210.0); 2.5023 (250.4); 2.3290 (1.6); 2.0744 (2.2); 1.6364 (3.4); 1.6191 (3.3); 1.1472 (0.8); 1.0767 (0.3); 0.9973 (0.8); −0.0003 (29.2) 640.3 [M + H].sup.+ I-266 [00455] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4981 (0.7); 9.4798 (0.7); 8.6052 (0.7); 8.4382 (1.0); 8.4346 (1.8); 8.4310 (1.0); 8.1443 (0.4); 8.1403 (0.4); 8.1218 (1.4); 8.1194 (1.3); 8.0681 (1.0); 7.8088 (1.3); 7.8074 (1.3); 7.7877 (1.2); 7.7862 (1.2); 6.1523 (0.5); 6.1346 (0.7); 6.1169 (0.5); 3.3494 (13.4); 3.3369 (88.7); 2.9935 (1.8); 2.9602 (16.0); 2.6766 (0.4); 2.6720 (0.6); 2.6674 (0.4); 2.5256 (1.9); 2.5209 (2.8); 2.5122 (34.6); 2.5077 (70.8); 2.5030 (93.4); 2.4984 (67.8); 2.4938 (32.7); 2.3344 (0.4); 2.3298 (0.6); 2.3252 (0.4); 2.0746 (1.7); 1.6327 (2.8); 1.6153 (2.8); 0.5274 (0.4); 0.4110 (0.4); 0.0081 (0.4); −0.0002 (15.1); −0.0085 (0.5) 596.2 [M + H].sup.+ I-267 [00456] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4974 (0.8); 9.4797 (0.8); 8.4898 (0.5); 8.4244 (1.6); 8.1109 (1.2); 8.0689 (1.4); 8.0317 (0.4); 7.8279 (1.6); 7.8069 (1.3); 6.1288 (0.5); 6.1114 (0.7); 6.0938 (0.5); 3.3502 (10.7); 3.3298 (147.8); 3.0626 (0.7); 2.9588 (16.0); 2.6758 (0.7); 2.6715 (0.9); 2.6671 (0.7); 2.5244 (4.7); 2.5112 (57.7); 2.5070 (108.8); 2.5025 (139.8); 2.4980 (103.4); 2.4938 (52.2); 2.3338 (0.6); 2.3293 (0.9); 2.3249 (0.6); 2.0746 (0.5); 1.6352 (3.0); 1.6178 (2.9); 0.5060 (0.4); 0.4522 (0.3); 0.4462 (0.3); 0.2929 (0.3); 0.0080 (0.9); −0.0002 (19.3); −0.0082 (0.8) 610.3 [M + H].sup.+ I-268 [00457] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.4984 (0.7); 9.4802 (0.8); 8.5142 (1.2); 8.5126 (1.3); 8.5086 (1.3); 8.5070 (1.3); 8.4247 (1.0); 8.4211 (1.8); 8.4175 (1.0); 8.3160 (0.5); 8.1090 (1.1); 8.0673 (1.1); 8.0615 (1.5); 8.0557 (0.9); 8.0403 (1.1); 8.0346 (1.1); 7.8230 (1.4); 7.8018 (1.2); 6.1252 (0.5); 6.1077 (0.8); 6.0900 (0.5); 3.3509 (9.4); 3.3285 (226.3); 3.0017 (1.7); 2.9573 (16.0); 2.9258 (1.8); 2.6802 (0.5); 2.6757 (1.1); 2.6712 (1.5); 2.6666 (1.1); 2.6621 (0.5); 2.6029 (0.4); 2.5247 (5.1); 2.5200 (7.4); 2.5112 (86.5); 2.5068 (174.5); 2.5022 (230.4); 2.4976 (167.1); 2.4931 (80.3); 2.3381 (0.5); 2.3336 (1.0); 2.3290 (1.4); 2.3244 (1.0); 2.3199 (0.5); 1.6356 (2.9); 1.6182 (2.8); 0.0081 (1.6); −0.0001 (53.6); −0.0084 (1.6) 570.2 [M + H].sup.+ I-269 [00458] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5185 (0.7); 9.5005 (0.8); 8.4934 (1.0); 8.4871 (1.0); 8.4487 (2.5); 8.3164 (1.2); 8.0426 (0.4); 8.0361 (0.4); 8.0208 (0.5); 8.0143 (0.5); 7.8437 (1.0); 7.8220 (0.8); 6.0806 (0.5); 6.0630 (0.8); 6.0453 (0.5); 3.3278 (33.8); 3.2178 (0.9); 2.9504 (16.0); 2.6719 (0.4); 2.5967 (0.4); 2.5255 (1.4); 2.5208 (2.1); 2.5121 (25.3); 2.5076 (50.9); 2.5030 (67.0); 2.4983 (48.8); 2.4938 (23.5); 2.3298 (0.4); 2.0754 (1.6); 1.6440 (2.9); 1.6267 (2.8); 0.8253 (0.4); 0.8205 (0.5); 0.8133 (0.8); 0.8088 (1.0); 0.7972 (0.6); 0.6099 (0.5); 0.0080 (0.4); −0.0002 (12.0); −0.0085 (0.3) 570.5 [M + H].sup.+ I-270 [00459] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3582 (0.8); 9.3402 (0.8); 8.4878 (1.0); 8.4817 (1.1); 8.1408 (1.3); 8.0995 (1.3); 8.0631 (1.3); 8.0411 (0.4); 8.0348 (0.4); 8.0193 (0.5); 8.0129 (0.5); 7.8380 (1.0); 7.8162 (0.8); 6.0416 (0.5); 6.0239 (0.8); 6.0063 (0.6); 3.3294 (54.7); 3.2250 (1.0); 2.9498 (16.0); 2.6763 (0.4); 2.6719 (0.5); 2.6673 (0.3); 2.5957 (0.4); 2.5253 (1.8); 2.5205 (2.6); 2.5119 (29.4); 2.5074 (57.8); 2.5029 (74.8); 2.4983 (54.4); 2.4938 (26.2); 2.3343 (0.3); 2.3296 (0.5); 2.3250 (0.3); 2.0751 (0.7); 1.6233 (3.0); 1.6060 (2.9); 0.8120 (1.1); 0.6202 (0.5); 0.6156 (0.5); 0.0079 (0.4); −0.0002 (12.2); −0.0086 (0.4) 536.0 [M + H].sup.+ I-271 [00460] .sup.1H-NMR (600.1 MHz, CD3CN 260 K): δ = 8.4535 (0.3); 8.2635 (0.6); 8.1207 (0.2); 8.1088 (0.2); 7.9868 (0.4); 7.9746 (0.5); 7.9373 (0.1); 7.9257 (0.2); 7.9228 (0.2); 7.9017 (0.3); 7.8875 (0.1); 6.1220 (0.1); 6.1102 (0.2); 6.0984 (0.1); 3.2260 (1.2); 3.1374 (3.1); 2.9836 (5.7); 2.2990 (5.0); 2.0979 (0.8); 1.9856 (0.4); 1.9775 (0.3); 1.9697 (5.8); 1.9656 (11.0); 1.9615 (16.0); 1.9574 (11.0); 1.9533 (5.6); 1.6460 (0.9); 1.6344 (1.0); 1.3587 (0.1); 1.3520 (0.1); 0.8640 (0.3); 0.8584 (0.3); 0.6121 (0.3); 0.5989 (0.3); −0.0001 (1.5) 596.2 [M + H].sup.+ I-272 [00461] .sup.1H-NMR (600.1 MHz, CD3CN 260 K): δ = 8.4133 (0.6); 8.4101 (0.6); 7.9236 (0.2); 7.9202 (0.2); 7.9092 (0.4); 7.9058 (0.4); 7.8760 (0.6); 7.8616 (0.3); 7.7802 (0.3); 7.7678 (0.3); 7.3882 (0.6); 7.3162 (0.7); 7.1663 (0.8); 6.0647 (0.3); 6.0528 (0.4); 6.0408 (0.3); 3.2034 (2.6); 2.9843 (10.0); 2.6159 (0.1); 2.3025 (7.0); 1.9944 (0.1); 1.9859 (0.6); 1.9778 (0.5); 1.9699 (6.0); 1.9658 (11.2); 1.9617 (16.0); 1.9576 (11.1); 1.9535 (5.6); 1.6214 (2.1); 1.6098 (2.1); 1.2714 (0.2); 1.2650 (0.2); 1.2586 (0.2); 1.0549 (0.8); 1.0511 (0.9); 1.0409 (0.8); 1.0371 (0.8); 0.8619 (0.2); 0.8500 (0.3); 0.8453 (0.3); 0.8269 (0.3); 0.8096 (0.1); 0.8033 (0.1); 0.7845 (0.1); 0.7779 (0.2); 0.7683 (0.3); 0.7647 (0.4); 0.7566 (0.4); 0.7475 (0.3); 0.7400 (0.3); 0.7253 (0.1); 0.5541 (0.5); 0.5413 (0.5); −0.0001 (1.5) 558.2 [M + H].sup.+ I-273 [00462] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5317 (0.9); 9.5141 (0.9); 8.4954 (1.5); 8.4903 (1.5); 8.4637 (3.1); 8.3154 (1.8); 8.0521 (0.9); 8.0465 (0.8); 8.0310 (1.0); 8.0254 (1.0); 7.8445 (1.5); 7.8234 (1.3); 6.1386 (0.6); 6.1212 (0.9); 6.1035 (0.6); 3.3249 (108.8); 2.9569 (16.0); 2.6899 (0.4); 2.6758 (1.0); 2.6714 (1.2); 2.6670 (0.9); 2.5243 (5.4); 2.5068 (148.9); 2.5024 (191.3); 2.4980 (143.6); 2.3336 (0.9); 2.3292 (1.2); 2.3249 (0.9); 1.6416 (3.3); 1.6243 (3.2); 1.3554 (0.4); 1.1371 (0.7); 1.0881 (0.4); 1.0708 (0.3); 1.0004 (0.6); 0.1461 (0.5); 0.0078 (5.2); −0.0001 (110.3); −0.0079 (5.0); −0.1494 (0.5) 614.3 [M + H].sup.+ I-274 [00463] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6053 (2.9); 9.5889 (3.0); 8.5465 (9.9); 8.5198 (16.0); 8.3426 (4.4); 8.3153 (0.5); 6.3945 (7.7); 5.9765 (0.4); 5.9596 (2.0); 5.9426 (3.0); 5.9257 (2.0); 5.9085 (0.4); 4.3639 (0.4); 4.3514 (0.8); 4.3385 (0.4); 3.4563 (0.8); 3.4436 (0.8); 3.4388 (0.8); 3.4261 (0.8); 3.4214 (0.3); 3.3290 (166.2); 2.6907 (2.1); 2.6768 (0.9); 2.6723 (1.2); 2.6678 (0.9); 2.6632 (0.4); 2.5256 (5.2); 2.5207 (8.4); 2.5123 (76.2); 2.5079 (147.4); 2.5033 (189.7); 2.4988 (136.8); 2.4943 (66.0); 2.3346 (0.8); 2.3302 (1.2); 2.3256 (0.8); 2.3212 (0.4); 1.6180 (10.6); 1.6006 (10.4); 1.2591 (0.4); 1.2431 (0.3); 1.0740 (1.6); 1.0565 (3.1); 1.0390 (1.5); 0.1459 (0.7); 0.0079 (6.5); −0.0002 (151.5); −0.0085 (5.0); −0.1496 (0.6) 476.3 [M + H].sup.+ I-275 [00464] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6422 (4.3); 9.6249 (4.4); 8.9223 (7.4); 8.9206 (7.8); 8.9168 (8.0); 8.9150 (7.4); 8.5197 (5.5); 8.5161 (9.9); 8.5126 (5.6); 8.4464 (6.5); 8.4408 (6.0); 8.4247 (6.8); 8.4191 (6.8); 8.3847 (6.0); 8.3163 (2.4); 8.1235 (5.8); 7.8286 (7.6); 7.8269 (7.8); 7.8070 (7.3); 7.8052 (7.5); 7.5761 (3.3); 7.4463 (8.2); 7.3166 (4.2); 6.1313 (0.7); 6.1137 (3.1); 6.0964 (4.9); 6.0792 (3.1); 6.0619 (0.7); 6.0021 (11.6); 3.3941 (0.5); 3.3297 (943.0); 2.6946 (0.3); 2.6895 (0.4); 2.6804 (2.2); 2.6760 (4.8); 2.6714 (6.6); 2.6669 (4.8); 2.6623 (2.3); 2.5250 (22.7); 2.5203 (32.9); 2.5115 (381.8); 2.5070 (768.6); 2.5024 (1011.5); 2.4978 (736.3); 2.4933 (354.4); 2.3383 (2.1); 2.3338 (4.6); 2.3292 (6.4); 2.3247 (4.5); 2.3202 (2.1); 2.0749 (2.6); 1.6165 (16.0); 1.5992 (16.0); 0.1459 (1.8); 0.0080 (14.9); −0.0002 (478.0); −0.0085 (14.6); −0.0231 (0.4); −0.1496 (1.8) 532.0 [M + H].sup.+ I-276 [00465] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6091 (2.4); 9.5915 (2.4); 8.8572 (15.5); 8.8451 (16.0); 8.4828 (3.2); 8.4792 (5.8); 8.4756 (3.4); 8.3497 (3.5); 8.3161 (1.2); 8.1097 (3.4); 7.5689 (2.0); 7.4420 (5.0); 7.4391 (5.1); 7.4300 (7.6); 7.4179 (4.0); 7.3093 (2.4); 6.0676 (0.4); 6.0502 (1.8); 6.0327 (2.9); 6.0152 (1.8); 5.9977 (0.4); 5.7548 (7.1); 3.3307 (425.2); 2.6807 (1.0); 2.6762 (2.0); 2.6716 (2.8); 2.6670 (2.0); 2.6625 (1.0); 2.5251 (9.4); 2.5204 (13.8); 2.5117 (159.5); 2.5072 (320.6); 2.5026 (421.0); 2.4980 (304.8); 2.4934 (145.2); 2.3386 (0.9); 2.3340 (1.9); 2.3294 (2.7); 2.3249 (1.9); 2.3204 (0.9); 1.6157 (9.7); 1.5984 (9.6); 0.1459 (0.8); 0.0080 (6.5); −0.0002 (209.8); −0.0086 (6.3); −0.0145 (0.5); −0.1496 (0.8) 508.0 [M + H].sup.+ I-277 [00466] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6309 (1.4); 9.6134 (1.5); 8.9733 (16.0); 8.4874 (3.2); 8.3599 (2.0); 8.3155 (0.4); 8.1168 (2.0); 7.5708 (1.1); 7.4409 (2.6); 7.3112 (1.3); 6.3440 (0.4); 6.3323 (1.4); 6.3196 (1.4); 6.3070 (0.4); 6.0170 (1.0); 5.9996 (1.6); 5.9822 (1.0); 3.3329 (284.8); 2.8917 (0.5); 2.7493 (6.7); 2.7368 (6.7); 2.6763 (0.8); 2.6718 (1.1); 2.6673 (0.8); 2.5252 (4.0); 2.5203 (6.4); 2.5118 (69.2); 2.5074 (135.1); 2.5028 (173.9); 2.4983 (126.0); 2.4939 (61.6); 2.3342 (0.8); 2.3297 (1.1); 2.3252 (0.8); 2.3207 (0.4); 1.6100 (5.3); 1.5927 (5.3); 0.1459 (0.5); 0.0079 (4.2); −0.0003 (115.3); −0.0085 (4.0); −0.1496 (0.5) 556.3 [M + H].sup.+ I-278 [00467] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.7183 (4.0); 9.7021 (4.1); 8.5371 (8.1); 8.5159 (16.0); 8.3933 (5.7); 8.3154 (1.0); 8.1401 (5.7); 7.5811 (2.6); 7.4515 (5.8); 7.3218 (3.0); 6.8893 (1.1); 6.8777 (3.7); 6.8652 (3.7); 6.8528 (1.1); 5.9757 (0.6); 5.9593 (2.4); 5.9422 (3.6); 5.9255 (2.4); 5.9085 (0.5); 3.4338 (0.4); 3.3312 (1027.0); 2.7521 (15.6); 2.7399 (15.7); 2.6711 (4.4); 2.6180 (0.4); 2.5064 (496.7); 2.5022 (673.4); 2.4982 (546.4); 2.3290 (4.1); 1.6149 (13.1); 1.5975 (13.1); 1.2334 (0.3); 0.1454 (2.0); 0.0077 (14.0); 0.0055 (13.9); −0.0004 (413.1); −0.1504 (2.0) 552.2 [M + H].sup.+ I-279 [00468] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6136 (2.7); 9.5956 (2.7); 8.8859 (15.6); 8.8738 (16.0); 8.4356 (3.6); 8.4320 (6.3); 8.4284 (3.5); 8.3155 (1.6); 8.3067 (3.8); 8.1055 (3.8); 7.5630 (2.2); 7.4804 (4.1); 7.4683 (7.7); 7.4562 (4.0); 7.4332 (5.1); 7.3035 (2.6); 6.0729 (0.4); 6.0554 (2.0); 6.0377 (3.1); 6.0201 (2.0); 6.0025 (0.4); 3.3790 (7.4); 3.3319 (702.6); 2.6809 (1.0); 2.6764 (2.1); 2.6718 (2.8); 2.6672 (2.0); 2.6627 (0.9); 2.5253 (9.8); 2.5206 (14.3); 2.5119 (165.6); 2.5074 (329.6); 2.5028 (426.5); 2.4982 (303.3); 2.4937 (142.8); 2.3388 (0.9); 2.3342 (2.0); 2.3297 (2.7); 2.3251 (1.9); 2.3207 (0.9); 1.6269 (10.7); 1.6096 (10.6); 1.5529 (13.5); 0.1460 (1.5); 0.0080 (11.8); −0.0001 (361.9); −0.0085 (11.5); −0.1496 (1.5) 576.4 [M + H].sup.+ I-280 [00469] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.6804 (2.5); 9.6624 (2.6); 8.8889 (15.7); 8.8768 (16.0); 8.4546 (3.4); 8.4511 (6.0); 8.4476 (3.5); 8.3198 (3.8); 8.3156 (4.7); 8.3075 (0.4); 8.1448 (0.4); 8.1062 (4.0); 8.0256 (0.3); 7.5645 (2.1); 7.4774 (4.1); 7.4653 (7.7); 7.4532 (4.5); 7.4346 (5.0); 7.3049 (2.5); 6.0883 (0.4); 6.0709 (1.9); 6.0532 (3.1); 6.0357 (2.0); 6.0183 (0.4); 5.7554 (1.5); 3.7421 (0.6); 3.5089 (0.4); 3.4923 (0.7); 3.4759 (0.5); 3.4363 (0.3); 3.3778 (4.9); 3.3615 (11.6); 3.3296 (1008.4); 2.6899 (1.5); 2.6805 (1.9); 2.6760 (3.9); 2.6714 (5.5); 2.6668 (4.0); 2.6622 (1.9); 2.5879 (1.0); 2.5249 (18.9); 2.5202 (28.1); 2.5115 (321.4); 2.5070 (644.2); 2.5024 (840.3); 2.4978 (603.8); 2.4933 (288.2); 2.3381 (1.8); 2.3338 562.3 [M + H].sup.+ (4.1); 2.3293 (5.5); 2.3247 (3.8); 2.3202 (1.7); 1.9106 (4.1); 1.9023 (4.5); 1.8943 (10.4); 1.8865 (4.6); 1.8777 (3.8); 1.8637 (0.7); 1.8529 (0.5); 1.8383 (0.4); 1.6428 (10.5); 1.6254 (10.4); 1.2546 (0.3); 1.2397 (0.4); 0.1459 (3.0); 0.0079 (24.8); −0.0002 (757.6); −0.0086 (25.0); −0.0153 (2.0); −0.0204 (1.3); −0.1496 (3.1) I-281 [00470] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.5923 (2.3); 9.5761 (2.4); 8.5207 (16.0); 8.4716 (3.2); 8.4679 (5.9); 8.4643 (3.2); 8.3158 (1.0); 8.1935 (3.2); 8.1911 (2.9); 8.0766 (3.2); 6.3984 (5.9); 5.9441 (1.6); 5.9272 (2.3); 5.9103 (1.6); 3.3286 (455.1); 3.3119 (1.1); 3.0744 (0.5); 3.0625 (1.0); 3.0548 (1.1); 3.0503 (0.7); 3.0431 (2.2); 3.0349 (0.8); 3.0310(1.2); 3.0233 (1.1); 3.0113 (0.6); 2.6804 (0.8); 2.6759 (1.9); 2.6713 (2.6); 2.6667 (1.9); 2.6621 (0.9); 2.5249 (8.2); 2.5202 (11.8); 2.5115 (149.2); 2.5069 (304.6); 2.5023 (401.4); 2.4977 (287.8); 2.4931 (136.0); 2.3383 (0.8); 2.3337 (1.8); 2.3292 (2.6); 2.3246 (1.8); 2.3201 (0.8); 1.6147 (8.3); 1.5973 (8.3); 1.2506 (0.4); 1.2382 (0.5); 1.2272 (1.2); 1.2242 (1.2); 1.2147 (2.4); 1.2060 (2.7); 1.1951 (1.8); 1.1845 (0.6); 1.1727 (0.5); 1.1584 (0.4); 1.1458 (0.6); 528.3 [M + H].sup.+ 1.1376 (0.8); 1.1228 (3.3); 1.1177 (2.6); 1.1032 (3.1); 1.0980 (2.2); 1.0805 (0.4); 0.1459 (1.4); 0.0135 (0.7); 0.0128 (0.7); 0.0081 (11.2); −0.0001 (370.2); −0.0085 (11.1); −0.0165 (0.6); −0.0245 (0.4); −0.1496 (1.4) I-282 [00471] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3660 (2.3); 9.3495 (2.3); 8.5140 (16.0); 8.3154 (1.8); 8.0462 (3.3); 8.0421 (5.2); 8.0381 (3.4); 7.8172 (3.4); 7.8146 (3.8); 7.8112 (4.0); 7.8086 (3.6); 7.8061 (3.4); 6.3912 (5.9); 5.9123 (0.3); 5.8952 (1.6); 5.8783 (2.3); 5.8612 (1.6); 3.3969 (0.4); 3.3298 (971.5); 2.6804 (1.5); 2.6759 (3.3); 2.6713 (4.5); 2.6667 (3.2); 2.6621 (1.6); 2.5884 (0.5); 2.5248 (15.1); 2.5201 (21.6); 2.5114 (256.8); 2.5069 (524.6); 2.5023 (689.5); 2.4977 (495.0); 2.4931 (234.5); 2.3382 (1.4); 2.3338 (3.1); 2.3291 (4.4); 2.3245 (3.1); 2.3200 (1.4); 1.5862 (8.5); 1.5688 (8.5); 0.1459 (2.5); 0.0279 (0.3); 0.0147 (1.1); 0.0080 (20.4); −0.0002 (662.6); −0.0086 (20.8); −0.0231 (0.7); −0.1496 (2.5) 458.3 [M + H].sup.+ I-283 [00472] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.1965 (2.7); 9.1800 (2.8); 8.5161 (16.0); 8.3155 (0.9); 7.5925 (5.6); 7.5890 (3.8); 7.5785 (3.3); 7.5760 (3.7); 7.2972 (3.6); 6.3745 (7.0); 5.9115 (0.4); 5.8943 (1.8); 5.8773 (2.8); 5.8602 (1.8); 5.8424 (0.4); 3.3324 (627.7); 2.6806 (0.9); 2.6761 (1.8); 2.6715 (2.6); 2.6670 (1.8); 2.6624 (0.9); 2.5251 (8.2); 2.5203 (12.1); 2.5116 (151.2); 2.5071 (301.2); 2.5026 (389.7); 2.4980 (278.3); 2.4934 (131.8); 2.3385 (0.8); 2.3340 (1.8); 2.3294 (2.4); 2.3248 (1.7); 2.3203 (0.8); 2.0873 (0.5); 2.0747 (1.1); 2.0662 (1.2); 2.0539 (2.2); 2.0412 (1.3); 2.0330 (1.2); 2.0204 (0.6); 1.5845 (9.8); 1.5670 (9.8); 1.0603 (0.9); 1.0490 (3.7); 1.0434 (4.0); 1.0327 (1.6); 1.0280 (3.8); 1.0225 (3.9); 1.0121 (1.1); 0.8124 (1.5); 0.8022 (3.6); 0.7987 (3.5); 0.7965 (3.5); 0.7898 (3.7); 0.7857 (3.4); 0.7740 464.4 [M + H].sup.+ (1.2); 0.1459 (1.0); 0.0080 (7.3); −0.0002 (236.4); −0.0085 (7.5); −0.1496 (1.0) I-284 [00473] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3020 (2.4); 9.2855 (2.5); 8.5155 (14.4); 8.3153 (0.6); 8.0761 (10.4); 8.0717 (16.0); 8.0571 (4.9); 8.0528 (5.4); 8.0484 (2.2); 6.3900 (6.3); 5.8946 (0.3); 5.8772 (1.7); 5.8602 (2.6); 5.8432 (1.7); 5.8256 (0.3); 3.3712 (0.4); 3.3321 (393.8); 2.6808 (0.5); 2.6763 (1.2); 2.6717 (1.6); 2.6672 (1.2); 2.6625 (0.6); 2.5253 (5.1); 2.5206 (7.4); 2.5118 (94.7); 2.5074 (193.0); 2.5028 (253.4); 2.4982 (182.7); 2.4936 (87.5); 2.3386 (0.5); 2.3342 (1.2); 2.3296 (1.6); 2.3250 (1.2); 2.3204 (0.5); 1.5713 (9.0); 1.5539 (9.0); 0.1459 (0.6); 0.0080 (4.8); −0.0002 (162.5); −0.0085 (5.1); −0.1496 (0.7) 498.1 [M + H].sup.+ I-285 [00474] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.3669 (3.0); 9.3507 (3.1); 8.5144 (16.0); 8.3153 (1.6); 8.1801 (3.8); 8.1763 (6.5); 8.1725 (3.9); 7.9097 (3.9); 7.8425 (4.0); 6.3909 (7.6); 5.9106 (0.4); 5.8938 (1.9); 5.8768 (3.0); 5.8597 (2.0); 5.8420 (0.4); 3.4371 (0.4); 3.3697 (1.6); 3.3331 (1546.8); 2.6806 (1.6); 2.6761 (3.3); 2.6716 (4.6); 2.6670 (3.4); 2.6624 (1.6); 2.5251 (14.7); 2.5203 (21.6); 2.5117 (273.7); 2.5072 (554.5); 2.5027 (724.7); 2.4981 (518.9); 2.4935 (247.6); 2.3385 (1.4); 2.3340 (3.2); 2.3294 (4.5); 2.3249 (3.2); 2.3204 (1.4); 2.0744 (1.0); 1.5845 (10.5); 1.5670 (10.5); 1.3695 (0.4); 0.1460 (1.6); 0.0081 (12.1); 0.0000 (387.1); −0.0084 (12.3); −0.1494 (1.7) 504.2 [M + H].sup.+ I-286 [00475] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.2470 (4.0); 9.2294 (4.1); 8.5084 (7.3); 8.5073 (7.6); 8.5020 (7.9); 8.5008 (7.6); 8.3181 (0.4); 8.1044 (6.1); 8.0978 (5.8); 8.0824 (6.6); 8.0758 (6.6); 7.9924 (5.8); 7.9883 (9.2); 7.9843 (6.1); 7.7701 (8.5); 7.7677 (8.0); 7.7646 (6.1); 7.7017 (8.2); 7.7004 (8.1); 7.6797 (7.6); 7.6784 (7.5); 6.0029 (0.6); 5.9858 (3.0); 5.9684 (4.9); 5.9509 (3.1); 5.9335 (0.6); 5.7965 (1.6); 5.7571 (3.0); 3.3406 (28.2); 2.6777 (0.7); 2.6731 (1.0); 2.6686 (0.7); 2.5593 (1.9); 2.5454 (4.1); 2.5315 (2.5); 2.5267 (3.3); 2.5220 (4.7); 2.5133 (57.6); 2.5088 (117.8); 2.5042 (154.7); 2.4995 (111.2); 2.4950 (52.7); 2.3356 (0.7); 2.3310 (1.0); 2.3263 (0.7); 1.5774 (16.0); 1.5600 (15.9); 1.2812 (0.5); 1.2639 (0.8); 1.2511 (0.3); 1.2470 (0.5); 0.1459 (0.4); 458.3 [M + H].sup.+ 0.0081 (3.1); −0.0001 (102.4); −0.0085 (3.1); −0.1495 (0.4) .sup.1)‘260 K’ denotes that the measurement was conducted at 260 Kelvin. .sup.2)The stated mass corresponds to the peak from the isotope pattern of the [M + H].sup.+ ion with the highest intensity. .sup.3)‘abs’ denotes that the compound was obtained in an enantiomerically enriched or pure form with the major stereoisomer having the absolute configuration depicted in the drawing.

TABLE-US-00003 TABLE 2 (Intermediates) Example Structure.sup.1) NMR data ESI Mass (m/z).sup.2) INT-001 [00476] 306.2 [M + H].sup.+ INT-002 [00477] 339.1 [M + H].sup.+ INT-003 [00478] 320.2 [M + H].sup.+ INT-004 [00479] 320.0 [M + H].sup.+ INT-005 [00480] 316.1 [M + H].sup.+ INT-006 [00481] 335.1 [M + H].sup.+ INT-007 [00482] 302.1 [M + H].sup.+ INT-008 [00483] 302.1 [M + H].sup.+ INT-009 [00484] 269.1 [M + H].sup.+ INT-010 [00485] 269.2 [M + H].sup.+ INT-0111 [00486] 257.2 [M + H].sup.+ INT-012 [00487] 270.1 [M + H].sup.+ INT-013 [00488] n.d. INT-014 [00489] 424.1 [M + H].sup.+ INT-015 [00490] 281.1 [M + H].sup.+ INT-016 [00491] 317.1 [M + H].sup.+ INT-017 [00492] 316.9 [M + H].sup.+ INT-018 [00493] 418.2 [M + H].sup.+ INT-019 [00494] 330.2 [M + H].sup.+ INT-020 [00495] n.d. INT-021 [00496] 220.1 [M − HCl].sup.+ INT-022 [00497] 234.2 [M + H].sup.+ INT-023 [00498] 276.2 [M − HCl].sup.+ INT-024 [00499] 244.2 [M − HCl].sup.+ INT-025 [00500] n.d. INT-026 [00501] 250.1 [M − HCl].sup.+ INT-027 [00502] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0074 (4.6); 9.0057 (4.8); 9.0020 (5.0); 9.0001 (4.6); 8.6886 (4.4); 8.5344 (4.1); 8.5288 (3.9); 8.5127 (4.3); 8.5072 (4.3); 7.9635 (4.8); 7.9618 (4.8); 7.9418 (4.6); 7.9400 (4.6); 5.3594 (0.6); 5.3428 (1.8); 5.3259 (1.8) ;5.3087 (0.6);3.7366 (5.5); 3.7254 (7.9); 3.7128 (6.5); 3.5684 (16.0); 3.4722 (0.3); 3.4523 (6.4); 3.4399 (7.6); 3.4285 (5.4); 3.3367 (104.3); 2.6773 (0.3); 2.6726 (0.5); 2.6681 (0.3); 2.5262 (1.4); 2.5214 (1.9); 2.5129 (27.0); 2.5084 (56.4); 2.5038 (74.7); 2.4991 (53.2); 2.4946 (25.1); 2.3351 (0.3); 2.3305 (0.4); 2.3259 (0.3); 1.6244 (0.6); 1.6116 (11.3); 1.5947 (11.1); −0.0002 (0.8) 300.2 [M − HCl].sup.+ INT-028 [00503] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0302 (8.4); 8.6536 (1.0); 5.2392 (0.5); 5.2224 (0.5); 3.5685 (0.8); 3.3430 (34.4); 3.0129 (16.0); 2.5220 (0.5); 2.5134 (6.3); 2.5089 (13.0); 2.5043 (16.9); 2.4997 (11.8); 2.4951 (5.4); 1.6075 (2.8); 1.5907 (2.7) 268.1 [M − HCl].sup.+ INT-029 [00504] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 9.0132 (16.0); 8.6489 (1.6); 8.6398 (1.6); 5.2336 (0.5); 5.2186 (0.6); 5.2030 (0.5); 3.9199 (2.4); 3.5683 (14.5); 2.7946 (13.7); 2.5266 (0.9); 2.5218 (1.4); 2.5131 (19.2); 2.5087 (39.3); 2.5041 (51.6); 2.4995 (37.4); 2.4949 (18.2); 2.3310 (0.3); 1.5948 (5.4); 1.5780 (5.4); 0.0079 (1.8); −0.0002 (52.0); −0.0086 (1.6) 254.1 [M − HCl].sup.+ INT-030 [00505] 206.1 [M − HCl].sup.+ INT-031 [00506] 260.2 [M − HCl].sup.+ INT-032 [00507] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.9258 (6.2); 8.9137 (6.2); 8.6853 (2.8); 8.6763 (2.8); 7.5400 (2.8); 7.5279 (5.2); 7.5157 (2.7); 5.2916 (0.4); 5.2775 (0.9); 5.2626 (1.2); 5.2469 (0.9); 5.2316 (0.4); 4.2233 (16.0); 3.5686 (1.0); 3.4459 (6.2); 2.6748 (0.4); 2.5283 (1.3); 2.5236 (2.0); 2.5150 (25.9); 2.5105 (52.8); 2.5059 (68.5); 2.5013 (48.2); 2.4967 (22.3); 2.3327 (0.4); 1.7648 (8.0); 1.6182 (10.8); 1.6013 (12.9); 1.5891 (10.9); −0.0002 (0.5) 274.2 [M − HCl].sup.+ INT-033 [00508] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.8169 (5.5); 8.6075 (16.0); 5.2418 (1.6); 5.2249 (1.6); 5.2090 (0.6); 3.7261 (6.8); 3.7149 (10.1); 3.7024 (8.0); 3.5936 (0.4); 3.5684 (15.3); 3.4446 (7.9); 3.4323 (9.7); 3.4210 (6.7); 3.3438 (57.0); 2.6728 (0.4); 2.6685 (0.4); 2.6531 (0.6); 2.5430 (0.3); 2.5263 (1.5); 2.5126 (28.1); 2.5084 (56.3); 2.5039 (73.4); 2.4994 (53.4); 2.4951 (26.4); 2.3307 (0.4); 2.3263 (0.3); 1.6301 (0.5); 1.6147 (12.8); 1.5978 (12.5); −0.0002 (0.4) 306.2 [M − HCl].sup.+ INT-034 [00509] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.7868 (4.1); 8.5721 (16.0); 7.0181 (1.0); 5.2013 (1.2); 3.5685 (10.4); 3.3878 (24.1); 2.7976 (10.7); 2.6735 (0.4); 2.5268 (1.5); 2.5135 (27.0); 2.5091 (50.8); 2.5046 (63.4); 2.5001 (44.7); 2.4956 (21.1); 2.3314 (0.4); 1.6037 (11.6); 1.5867 (11.4) 250.1 [M − HCl].sup.+ INT-035 [00510] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.6965 (4.6); 8.6747 (1.5); 8.5848 (0.6); 8.5708 (16.0); 8.3234 (0.4); 8.2507 (0.9); 7.3390 (1.6); 7.2117 (1.9); 7.0843 (1.6); 6.5522 (1.1); 5.2004 (1.1); 5.1862 (1.4); 5.1706 (1.1); 3.5681 (8.6); 3.5024 (0.4); 3.4901 (0.5); 3.4719 (0.7); 3.4617 (0.8); 3.3849 (69.6); 2.6768 (0.9); 2.6722 (1.2); 2.6678 (0.9); 2.5255 (4.2); 2.5120 (77.9); 2.5078 (152.0); 2.5033 (196.5); 2.4988 (144.5); 2.4946 (72.1); 2.3345 (0.8); 2.3301 (1.2); 2.3255 (0.8); 1.6790 (0.4); 1.6689 (0.6); 1.6520 (0.6); 1.6226 (0.8); 1.5982 (12.9); 1.5813 (12.7); 1.2346 (0.5); −0.0003 (7.2) 236.1 [M − HCl].sup.+ INT-036 [00511] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.9997 (1.4); 8.9987 (1.4); 8.9942 (1.4); 8.6467 (1.4); 8.5193 (1.0); 8.5136 (1.0); 8.4977 (1.1); 8.4919 (1.0); 7.9443 (1.4); 7.9227 (1.3); 5.3583 (0.9); 5.3413 (0.9); 3.9130 (8.3); 3.5687 (3.0); 3.3328 (17.5); 3.0343 (16.0); 2.6727 (0.4); 2.5262 (0.6); 2.5127 (10.1); 2.5084 (19.5); 2.5038 (25.0); 2.4993 (18.3); 2.4950 (9.0); 1.6214 (3.3); 1.6045 (3.2); 0.0078 (0.6); −0.0002 (16.9); −0.0086 (0.6) 291.5 [M − HCl].sup.+ INT-037 [00512] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO): δ = 8.5478 (1.7); 8.5421 (1.7); 8.1004 (0.4); 8.0941 (0.3); 8.0789 (0.4); 8.0728 (0.4); 7.8919 (0.9); 7.8700 (0.7); 5.3057 (0.3); 3.5681 (10.6); 3.3463 (62.6); 3.3089 (0.4); 3.2803 (0.8); 3.0193 (16.0); 2.9701 (0.8); 2.6761 (0.4); 2.6715 (0.6); 2.6669 (0.4); 2.6598 (0.5); 2.5250 (2.1); 2.5202 (3.2); 2.5116 (38.2); 2.5071 (75.5); 2.5025 (98.0); 2.4979 (70.6); 2.4934 (33.8); 2.3341 (0.4); 2.3294 (0.6); 2.3249 (0.4); 1.6129 (3.1); 1.5961 (2.9); 0.8650 (0.4); 0.8549 (0.9); 0.8474 (1.2); 0.8363 (1.0); 0.8288 (0.4); 0.7020 (0.5); 0.0079 (1.0); −0.0002 (31.1); −0.0086 (1.0) 330.4 [M − HCl].sup.+ INT-038 [00513] 239.0 [M − HCl].sup.+ INT-039 [00514] .sup.1H NMR (400 MHz, d.sub.6-DMSO ) δ 7.47 (t, 1H), 8.21 (s, 1H), 8.32 (s, 1H), 8.40 (s, 1H), 13.79 (s, 1H). 319.0 [M + H].sup.+ .sup.1)‘(S)’ denotes that the compound was obtained in an enantiomerically enriched or pure form with the major stereoisomer having the absolute configuration depicted in the drawing. .sup.2)The stated mass corresponds to the peak from the isotope pattern of the [M + H].sup.+ ion with the highest intensity. n.d. = not determined.

BIOLOGICAL EXAMPLES

Rhipicephalus (Boophilus) Microplus—In-Vitro Contact Tests Larval Cattle Tick (Strain Parkhurst, Resistant Against Synthetic Pyrethroids)

[1454] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm.sup.2 and a homogeneous distribution, a dose of 5 μg/cm.sup.2 is achieved.

[1455] After the solvent has evaporated, each test tube is filled with 20-50 cattle tick larvae (Rhipicephalus microplus), closed with a perforated lid and incubated in a horizontal position at 85% relative humidity and 27° C. in an incubator. After 48 hours efficacy is determined. The larvae are patted on the ground of the tubes and negative geotactic behaviour is recorded. Larvae that climb back to the top of the vial in a manner comparable to untreated control larvae are marked as alive, larvae not climbing back up comparable to untreated control larvae but are moving uncoordinatedly or only twitching their legs are marked as moribund, tick larvae remaining on the bottom and not moving at all are counted as dead.

[1456] A compound shows a good efficacy against Rhipicephalus microplus, if at a compound concentration of 5 μg/cm.sup.2 an efficacy of at least 80% is monitored. An efficacy of 100% means all larvae are dead or moribund; 0% means no larvae are dead or moribund.

[1457] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-006, I-007, I-009, I-010, I-011, I-012, I-014, I-016, I-018, I-035, I-036, I-040, I-059, I-062, I-069, I-070, I-075, I-079, I-081, I-088, I-092, I-093, I-095, I-100, I-101, I-103, I-104, I-105, I-112, I-114, I-115, I-116, I-117, I-118, I-121, I-122, I-124, I-127, I-129, I-130, I-131, I-132, I-133, I-134, I-136, I-138, I-139, I-140, I-141, I-144, I-145, I-147, I-154, I-155, I-158, I-159, I-161.

[1458] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-004, I-013, I-022, I-027, I-071, I-076, I-078, I-090, I-097, I-099, I-108, I-113, I-120, I-123, I-146, I-148.

[1459] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): 1-053, 1-058, 1-089, 1-106, 1-137.

Rhipicephalus (Boophilus) Microplus—Dip Test

[1460] Test animal: cattle ticks (Rhipicephalus microplus) strain Parkhurst, SP-resistant

[1461] Solvent: dimethyl sulfoxide

[1462] To produce a suitable preparation of active compound, 10 mg of active compound are dissolved in 0.5 mL solvent, and the concentrate is diluted with water to the desired concentration.

[1463] This compound solution is pipetted into tubes. 8-10 engorged, adult, female cattle ticks (Rhipicephalus microplus) are placed in perforated tubes. These tubes are immersed in the aqueous compound solution until the ticks are completely moistened. After the liquid has drained off, the ticks are transferred to a filter paper in a plastic tray and stored in a climate chamber.

[1464] After 7 days egg deposition of fertile eggs is monitored. Eggs where fertility is not visible are stored in a climate chamber till hatching after about 42 days. An efficacy of 100% means all eggs are infertile; 0% means all eggs are fertile.

[1465] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 ppm: I-088.

[1466] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 100 ppm: I-004, I-009, I-013.

Rhipicephalus (Boophilus) Microplus—Injection Test

[1467] Solvent: dimethyl sulfoxide

[1468] To produce a suitable preparation of active compound, 10 mg of active compound are dissolved in 0.5 mL solvent, and the concentrate is diluted with solvent to the desired concentration.

[1469] Five adult engorged female ticks (Rhipicephalus microplus) are injected with 1 μL compound solution into the abdomen. The ticks are transferred into replica plates and incubated in a climate chamber.

[1470] After 7 days egg deposition of fertile eggs is monitored. Eggs where fertility is not visible are stored in a climate chamber till hatching after about 42 days. An efficacy of 100% means all eggs are infertile; 0% means all eggs are fertile.

[1471] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 20 μg/animal: I-001, I-002, I-003, I-005, I-006, I-010, I-011, I-012, I-013, I-014, I-015, I-016, I-017, I-018, I-026, I-027, I-028, I-029, I-030, I-035, I-036, I-037, I-038, I-040, I-042, I-044, I-045, I-046, I-047, I-049, I-050, I-051, I-052, I-054, I-055, I-056, I-057, I-058, I-059, I-060, I-062, I-063, I-065, I-066, I-067, I-068, I-069, I-070, I-071, I-076, I-077, I-078, I-079, I-121.

[1472] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 20 μg/animal: I-039.

[1473] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 4 μg/animal: I-001, I-002, I-004, I-005, I-006, I-007, I-008, I-009, I-010, I-011, I-012, I-013, I-014, I-015, I-016, I-017, I-018, I-019, I-020, I-022, I-026, I-028, I-029, I-030, I-037, I-038, I-039, I-040, I-044, I-045, I-046, I-047, I-048, I-050, I-051, I-052, I-058, I-059, I-060, I-062, I-063, I-065, I-066, I-069, I-070, I-071, I-074, I-075, I-076, I-077, I-078, I-079, I-080, I-081, I-082, I-088, I-089, I-090, I-091, I-092, I-093, I-096, I-097, I-098, I-099, I-100, I-101, I-102, I-103, I-104, I-105, I-117, I-118, I-121.

[1474] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 4 μg/animal: I-003, I-021, I-027, I-043, I-049, I-056, I-057, I-068.

Ctenocephalides felis—In-Vitro Contact Tests Adult Cat Flea

[1475] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm.sup.2 and a homogeneous distribution, a dose of 5 μg/cm.sup.2 is achieved.

[1476] After the solvent has evaporated, each test tube is filled with 5-10 adult cat fleas (Ctenocephalides felis), closed with a perforated lid and incubated in a lying position at room temperature and relative humidity. After 48 hours efficacy is determined. The fleas are patted on the ground of the tubes and are incubated on a heating plate at 45-50° C. for at most 5 minutes. Immotile or uncoordinated moving fleas, which are not able to escape the heat by climbing upwards, are marked as dead or moribund.

[1477] A compound shows a good efficacy against Ctenocephalides felis, if at a compound concentration of 5 μg/cm.sup.2 an efficacy of at least 80% is monitored. An efficacy of 100% means all fleas are dead or moribund; 0% means no fleas are dead or moribund.

[1478] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-004, I-006, I-007, I-018, I-022, I-062, I-076, I-088, I-091, I-092, I-099, I-100, I-101, I-103, I-104, I-105, I-115, I-121, I-123, I-127, I-128, I-129, I-130, I-131, I-132, I-133, I-134, I-138, I-139, I-140, I-141, I-154, I-155.

[1479] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-009, I-075, I-077, I-089, I-090, I-095, I-097, I-107, I-112, I-118, I-137, I-144.

[1480] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): 1-038, 1-059, 1-071, 1-079, 1-093, 1-145.

Ctenocephalides felis—Oral Test

[1481] Solvent: dimethyl sulfoxide

[1482] To produce a suitable preparation of active compound, 10 mg of active compound are dissolved in 0.5 mL solvent, and the concentrate is diluted with cattle blood to the desired concentration.

[1483] Approximately 20 adult unfed cat fleas (Ctenocephalides felis) are placed in flea chambers. The blood chamber, sealed with parafilm on the bottom, are filled with cattle blood supplied with compound solution and placed on the gauze covered top of the flea chamber, so that the fleas are able to suck the blood. The blood chamber is heated to 37° C. whereas the flea chamber is kept at room temperature.

[1484] After 2 days mortality in % is determined. 100% means all the fleas have been killed; 0% means none of the fleas have been killed.

[1485] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 ppm: I-004, I-005, I-006, I-007, I-008, I-009, I-010, I-011, I-012, I-013, I-014, I-015, I-016, I-017, I-018, I-019, I-020, I-021, I-022, I-027, I-028, I-029, I-030, I-035, I-036, I-038, I-039, I-040, I-044, I-045, I-046, I-047, I-048, I-049, I-050, I-051, I-053, I-054, I-055, I-056, I-057, I-066, I-074, I-075, I-076, I-077, I-078, I-079, I-080, I-082, I-088, I-089, I-090, I-091, I-092, I-097, I-099, I-100, I-101, I-103, I-104, I-105, I-117, I-118, I-121.

[1486] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 ppm: I-019, I-037, I-042, I-081, I-083, I-093.

[1487] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 100 ppm: I-058.

Rhipicephalus sanguineus—In-Vitro Contact Tests with Adult Brown Dog Ticks

[1488] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm.sup.2 and a homogeneous distribution, a dose of 5 μg/cm.sup.2 is achieved.

[1489] After the solvent has evaporated, each test tube is filled with 5-10 adult brown dog ticks (Rhipicephalus sanguineus), closed with a perforated lid and incubated in a lying position at room temperature and relative humidity. After 48 hours efficacy is determined. The ticks are patted on the ground of the tubes and are incubated on a heating plate at 45-50° C. for at most 5 minutes. Immotile or uncoordinated moving ticks, which are not able to escape the heat by climbing upwards, are marked as dead or moribund.

[1490] A compound shows a good efficacy against Rhipicephalus sanguineus, if at a compound concentration of 5 μg/cm.sup.2 an efficacy of at least 80% is monitored. An efficacy of 100% means all ticks are dead or moribund; 0% means no ticks are dead or moribund.

[1491] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-006, I-007, I-009, I-010, I-012, I-022, I-062, I-088, I-092, I-100, I-101, I-103, I-104, I-115, I-120, I-127, I-130, I-131, I-132, I-134, I-136, I-138, I-139, I-140, I-141, I-155.

[1492] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 5 μg/cm.sup.2 (=500 g/ha): I-011, I-032, I-045, I-099, I-126, I-129, I-154.

[1493] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 1 μg/cm.sup.2 (=100 g/ha): I-007, I-010, I-012, I-022, I-088, I-092, I-100, I-101, I-103, I-104, I-115, I-120, I-127, I-130, I-131, I-132, I-134, I-136, I-138, I-140, I-155, I-159.

[1494] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 μg/cm.sup.2 (=100 g/ha): I-006, I-009, I-093, I-129, I-139, I-141, I-154.

Diabrotica balteata—Spray Test

[1495] Solvent: 78.0 parts by weight of acetone [1496] 1.5 parts by weight of dimethylformamide

[1497] Emulsifier: alkylarylpolyglycol ether

[1498] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[1499] Soaked wheat seeds (Triticum aestivum) are placed in a multiple well plate filled with agar and some water and are incubated for 1 day to germinate (5 seeds per well). The germinated wheat seeds are sprayed with a test solution containing the desired concentration of the active ingredient. Afterwards each unit is infected with 10-20 larvae of the banded cucumber beetle (Diabrotica balteata).

[1500] After 7 days efficacy in % is determined. 100% means all the seedlings have grown up like in the untreated, uninfected control; 0% means none of the seedlings have grown.

[1501] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha (=160 μg/well): I-001, I-006, I-010, I-011, I-012, I-016, I-018, I-026, I-051, I-055, I-059, I-061, I-062, I-063, I-064.

[1502] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha (=32 μg/well): I-004, I-006, I-007, I-009, I-010, I-011, I-012, I-016, I-018, I-023, I-024, I-059, I-062, I-063, I-064, I-075, I-078, I-080, I-081, I-083, I-086, I-088, I-089, I-090, I-091, I-092, I-095, I-097, I-099, I-100, I-101, I-103, I-104, I-105, I-108, I-113, I-114, I-117, I-118, I-121, I-122, I-123, I-124, I-126, I-127, I-128, I-129, I-130, I-131, I-132, I-133, I-134, I-136, I-137, I-138, I-139, I-140, I-141, I-142, I-143, I-144, I-145, I-146, I-147, I-148, I-149, I-150, I-151, I-152, I-154, I-155, I-156, I-158, I-159, I-161, I-162, I-163, I-164, I-165, I-166, I-167, I-168, I-170, I-172, I-173, I-174, I-175, I-176, I-177, I-178, I-179, I-180, I-182, I-183, I-184, I-185, I-186, I-187, I-190, I-191, I-192, I-193, I-194, I-195, I-197, I-199, I-202, I-203.

[1503] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 100 g/ha (=32 μg/well): 1-055, 1-082, 1-093, 1-094, 1-115, 1-198.

Meloidogyne incognita—Test

[1504] Solvent: 125.0 parts by weight of acetone

[1505] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water to the desired concentration.

[1506] Vessels are filled with sand, a solution of the active ingredient, a suspension containing eggs and larvae of the southern root-knot nematode (Meloidogyne incognita) and salad seeds. The salad seeds germinate and the seedlings grow. Galls develop in the roots.

[1507] After 14 days the nematicidal activity is determined on the basis of the percentage of gall formation. 100% means no galls were found and 0% means the number of galls found on the roots of the treated plants was equal to that in untreated control plants.

[1508] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 20 ppm: I-051, I-128, I-145, I-146, I-147.

[1509] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 20 ppm: I-054, I-055, I-064, I-066, I-076, I-077, I-078, I-123, I-130, I-132, I-144.

Myzus persicae—Oral Test

[1510] Solvent: 100 parts by weight acetone

[1511] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water to the desired concentration.

[1512] 50 μL compound solution is filled in microtiter plates and 150 μL IPL41 insect medium (33%+15% sugar) is added to obtain a total volume of 200 μL per well. Afterwards the plates are sealed with parafilm through which a mixed population of the green peach aphid (Myzus persicae) can suck on the compound preparation.

[1513] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[1514] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 4 ppm: I-004, I-006, I-007, I-009, I-011, I-012, I-017, I-022, I-023, I-024, I-027, I-051, I-057, I-058, I-059, I-060, I-061, I-063, I-064, I-074, I-076, I-077, I-079, I-088, I-089, I-091, I-092, I-093, I-094, I-095, I-097, I-099, I-100, I-101, I-103, I-104, I-105, I-108, I-117, I-118.

[1515] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 4 ppm: I-005, I-010, I-019, I-020, I-025, I-045, I-053, I-054, I-078, I-080, I-107, I-114, I-116.

Myzus persicae—Spray Test

[1516] Solvent: 78.0 parts by weight acetone [1517] 1.5 parts by weight dimethylformamide

[1518] Emulsifier: alkylarylpolyglycol ether

[1519] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[1520] Chinese cabbage (Brassica pekinensis) leaf disks infected with all instars of the green peach aphid (Myzus persicae), are sprayed with a preparation of the active ingredient of the desired concentration.

[1521] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[1522] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-012, I-061, I-095.

[1523] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-088, I-097, I-130, I-134, I-155, I-163.

[1524] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 g/ha: I-007, I-076, I-077, I-090, I-092, I-101, I-103, I-127, I-129, I-132, I-138, I-140, I-148, I-152, I-153, I-165, I-178, I-179, I-184, I-187, I-192, I-202, I-205, I-216.

Nezara viridula—Spray Test

[1525] Solvent: 78.0 parts by weight of acetone [1526] 1.5 parts by weight of dimethylformamide

[1527] Emulsifier: alkylarylpolyglycol ether

[1528] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[1529] Barley plants (Hordeum vulgare) infested with larvae of the southern green stink bug (Nezara viridula) are sprayed with a test solution containing the desired concentration of the active ingredient.

[1530] After 4 days mortality in % is determined. 100% means all the stink bugs have been killed; 0% means none of the stink bugs have been killed.

[1531] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-006, I-012, I-017, I-027, I-051, I-055, I-059, I-060, I-061, I-062, I-063, I-064, I-115, I-116, I-117, I-118, I-123, I-126, I-127, I-129, I-130, I-131, I-132, I-133, I-134, I-137, I-139, I-141, I-142, I-143, I-145, I-146, I-148, I-149, I-151, I-152, I-153, I-154, I-155, I-156, I-162, I-163, I-164, I-165, I-166, I-167, I-168, I-169, I-170, I-171, I-176, I-177, I-178, I-179, I-180, I-183, I-184, I-185, I-186, I-187, I-188, I-189, I-190, I-192, I-193, I-194, I-195, I-202, I-203, I-204, I-211.

[1532] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-011, I-026, I-095. I-136, I-140, I-157, I-159, I-173, I-191, I-196.

[1533] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-006, I-007, I-009, I-012, I-027, I-051, I-055, I-059, I-060, I-061, I-062, I-064, I-074, I-076, I-077, I-088, I-092, I-097, I-103.

[1534] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 g/ha: I-017, I-019, I-021, I-023, I-084.

Nilanarvata lugens—Spray Test

[1535] Solvent: 78.0 parts by weight of acetone [1536] 1.5 parts by weight of dimethylformamide

[1537] Emulsifier: alkylarylpolyglycol ether

[1538] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[1539] Rice plants (Oryza sativa) are sprayed with a preparation of the active ingredient of the desired concentration and the plants are infested with the brown planthopper (Nilaparvata lugens).

[1540] After 4 days mortality in % is determined. 100% means all planthoppers have been killed and 0% means none of the planthoppers have been killed.

[1541] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-133, I-134, I-136, I-138, I-139, I-141, I-148, I-149, I-151, I-152, I-153, I-155, I-160, I-163, I-165, I-168, I-169, I-170, I-173, I-174, I-175, I-176, I-177, I-178, I-179, I-180, I-181, I-182, I-183, I-184, I-185, I-186, I-187, I-188, I-189, I-192, I-202, I-211.

[1542] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-006, I-121, I-127, I-128, I-129, I-130, I-131, I-137, I-140.

[1543] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-088.

[1544] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 g/ha: I-077.

Spodoptera frugiperda—Spray Test

[1545] Solvent: 78.0 parts by weight acetone [1546] 1.5 parts by weight dimethylformamide

[1547] Emulsifier: alkylarylpolyglycol ether

[1548] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[1549] Maize (Zea mays) leaf sections are sprayed with a preparation of the active ingredient of the desired concentration. Once dry, the leaf sections are infested with fall armyworm larvae (Spodoptera frugiperda).

[1550] After 7 days mortality in % is determined. 100% means all caterpillars have been killed and 0% means none of the caterpillars have been killed.

[1551] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-001, I-006, I-010, I-011, I-012, I-014, I-015, I-016, I-017, I-029, I-036, I-046, I-051, I-059, I-062, I-063, I-064.

[1552] In this test, for example, the following compounds from the preparation examples showed good activity of 83% at an application rate of 500 g/ha: I-047, I-048.

[1553] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-006, I-007, I-009, I-010, I-011, I-012, I-014, I-015, I-016, I-022, I-023, I-024, I-029, I-036, I-063, I-064, I-076, I-078, I-079, I-088, I-089, I-090, I-091, I-092, I-094, I-097, I-099, I-100, I-101, I-103, I-104, I-105, I-108, I-114, I-115, I-117, I-118, I-121, I-123, I-124, I-126, I-127, I-129, I-130, I-131, I-132, I-133, I-134, I-136, I-137, I-138, I-139, I-140, I-141, I-142, I-143, I-145, I-146, I-148, I-149, I-150, I-151, I-152, I-154, I-155, I-156, I-158, I-159, I-162, I-163, I-164, I-165, I-166, I-167, I-168, I-170, I-171, I-172, I-173, I-175, I-176, I-177, I-178, I-179, I-180, I-182, I-183, I-186, I-190, I-192, I-193, I-194, I-202, I-203, I-204, I-205, I-206, I-207, I-208, I-209, I-210, I-212, I-216.

[1554] In this test, for example, the following compounds from the preparation examples showed good activity of 83% at an application rate of 100 g/ha: I-093.

Tetranychus urticae—Spray Test OP-Resistant

[1555] Solvent: 78.0 parts by weight acetone [1556] 1.5 parts by weight dimethylformamide

[1557] Emulsifier: alkylarylpolyglycol ether

[1558] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.

[1559] French bean (Phaseolus vulgaris) leaf disks infected with all instars of the two spotted spidermite (Tetranychus urticae), are sprayed with a preparation of the active ingredient of the desired concentration.

[1560] After 6 days mortality in % is determined. 100% means all spider mites have been killed and 0% means none of the spider mites have been killed.

[1561] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-064.

[1562] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-003, I-012, I-016.

Spodoptera frugiperda—Spray Test

[1563] Solvent: 14 parts by weight of dimethylformamide

[1564] Emulsifier: alkylaryl polyglycol ether

[1565] To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water. Ammonium salt and/or penetration enhancer in a dosage of 1000 ppm are added to the desired concentration if necessary.

[1566] Cotton leaves (Gossypium hirsutum) are treated by being sprayed with the preparation of the active compound of the desired concentration and are infested with caterpillars of the fall army worm (Spodoptera frugiperda).

[1567] After 7 days mortality in % is determined. 100% means all the caterpillars have been killed and 0% means none of the caterpillars have been killed.

[1568] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 20 ppm: I-006, I-011, I-012, I-013, I-015, I-016, I-018, I-029, I-062, I-063, T-064, I-097, I-099, I-101, I-103, I-104, I-105, I-114, I-117, I-118, I-129, I-130, I-132, I-136, I-139, I-140, I-142, I-143, I-152, I-154, I-155.

[1569] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 20 ppm: I-010, I-092.

Aedes aegypti Test (AEDSAE Surface Treatment & Contact Assay)

[1570] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[1571] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult mosquitoes of the species Aedes aegypti strain MONHEIM are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[1572] The following examples showed in this test efficacy of 90-100% at a surface concentration of 20 mg/m.sup.2: I-006, I-088, I-138.

[1573] The following examples showed in this test efficacy of 90-100% at a surface concentration of 4 mg/m.sup.2: I-006, I-088, I-138.

Anopheles funestus Test (ANPHFU Surface Treatment & Contact Assay)

[1574] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[1575] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult mosquitoes of the species Anopheles funestus strain FUMOZ-R (Hunt et al., Med. Vet. Entomol. 2005 September; 19(3): 271-275) are placed onto the dried surface. The exposure time is 30 minutes.

[1576] Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[1577] The following examples showed in this test efficacy of 90-100% at a surface concentration of 20 mg/m.sup.2: I-088, I-138.

[1578] The following examples showed in this test efficacy of 90-100% at a surface concentration of 4 mg/m.sup.2: I-088.

Musca domestica Test (MUSCDO Surface Treatment & Contact Assay)

[1579] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[1580] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult flies of the species Musca domestica strain WHO-N are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[1581] The following examples showed in this test efficacy of 90-100% at a surface concentration of 20 mg/m.sup.2: I-006, I-088, I-138.

[1582] The following examples showed in this test efficacy of 90-100% at a surface concentration of 4 mg/m.sup.2: I-006, I-088, I-138.

Blattella germanica Test (BLTTGE Surface Treatment & Contact Assay)

[1583] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[1584] In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult animals of the species Blattella germanica strain PAULINIA are placed onto the dried surface. The exposure time is 30 minutes.

[1585] Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.

[1586] The following examples showed in this test efficacy of 90-100% at a surface concentration of 20 mg/m.sup.2: I-088, I-138.

[1587] The following examples showed in this test efficacy of 90-100% at a surface concentration of 4 mg/m.sup.2: I-088, I-138.