ALKYLAMIDE SUBSTITUTED, ANNULATED IMIDAZOLES AND USE THEREOF AS INSECTICIDES

Abstract

The present invention relates to novel alkylamide substituted, annulated imidazole derivatives of the general formula (I), in which the structural elements A.sub.1; A.sub.2, A.sub.3, A.sub.4, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 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. A compound of general formula (I) ##STR00101## in which X is O or S; A.sub.1 is N or CR.sup.5; A.sub.2 is N or CR.sup.5; A.sub.3 is N or CR.sup.5; A.sub.4 is N or CR.sup.5; wherein at least one or two of A.sub.1, A.sub.2, A.sub.3, A.sub.4 represents a nitrogen (N); R.sup.1 is hydrogen; or in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycloalkylC.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 haloalkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.2-C.sub.6 haloalkynyl; or phenyl-C.sub.1-C.sub.6 alkyl, in which phenyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, hydroxy, CN, COOH, CONH.sub.2, CSNH.sub.2, NO.sub.2, Si(CH.sub.3).sub.3, SF.sub.5, NH.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycanocycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cycloalkyl-C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl, C.sub.1-C.sub.3 cyanoalkylthio, C.sub.1-C.sub.3 cyanoalkylsulfinyl, and C.sub.1-C.sub.3 cyanoalkylsulfonyl; or heterocyclyl-C.sub.1-C.sub.6 alkyl, wherein the heterocyclyl is selected from the group consisting of saturated and partially unsaturated 3- to 10-membered heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl and the heterocyclyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, hydroxy, CN, COOH, CONH.sub.2, CSNH.sub.2, NO.sub.2, Si(CH.sub.3).sub.3, SF.sub.5, NH.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycanocycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cycloalkyl-C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl, C.sub.1-C.sub.3 cyanoalkylthio, C.sub.1-C.sub.3 cyanoalkylsulfinyl, and C.sub.1-C.sub.3 cyanoalkylsulfonyl; R.sup.2 is phenyl or a 5- or 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, hydroxy, CN, COOH, NO.sub.2, NH.sub.2, SO.sub.2NH.sub.2, SF.sub.5; and in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.6 cycloalkoxy, C.sub.1-C.sub.6 haloalkoxy, hydroxy-C.sub.1-C.sub.6 alkyl, CO.sub.2C.sub.1-C.sub.6 alkyl, NH(C.sub.1-C.sub.6 alkyl), N(C.sub.1-C.sub.6 alkyl).sub.2, SC.sub.1-C.sub.6 alkylsulfinimidoyl, SC.sub.3-C.sub.6 cycloalkylsulfinimidoyl, SC.sub.2-C.sub.6 alkenylsulfinimidoyl, SC.sub.2-C.sub.6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, SC.sub.1-C.sub.6 alkylsulfonimidoyl, SC.sub.3-C.sub.6 cycloalkylsulfonimidoyl, SC.sub.2-C.sub.6 alkenylsulfonimidoyl, SC.sub.2-C.sub.6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, C(?NOC.sub.1-C.sub.6 alkyl)H, C(?NOC.sub.1-C.sub.6 alkyl)-C.sub.1-C.sub.6 alkyl, and (C.sub.1-C.sub.6 alkyl).sub.3-silyl; and the substructures S1-S9, in which the bond to the phenyl or 5- or 6-membered heteroaryl is marked with a # and Z is CO or CS and Y is independently selected from CO and SO.sub.2; ##STR00102## wherein R.sup.21 is hydrogen or in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, phenyl, heteroaryl and heterocyclyl; R.sup.22 is hydrogen or in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl and C.sub.3-C.sub.6 cycloalkyl; R.sup.23 is independently selected from in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl and phenyl; R.sup.24 is in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, phenyl, heteroaryl and heterocyclyl; or R.sup.21 and R.sup.22 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic optionally substituted 3- to 12-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms; and 3- to 6-membered heterocyclyl or a 5- to 6-membered heteroaryl each containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein the 3- to 6-membered heterocyclyl or the 5- to 6-membered heteroaryl substituent may optionally carry 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, hydroxy, CN, COOH, CONH.sub.2, CSNH.sub.2, NO.sub.2, Si(CH.sub.3).sub.3, SF.sub.5, NH.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycanocycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cycloalkyl-C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl, C.sub.1-C.sub.3 cyanoalkylthio, C.sub.1-C.sub.3 cyanoalkylsulfinyl, and C.sub.1-C.sub.3 cyanoalkylsulfonyl; R.sup.3 is hydrogen, or C.sub.1-C.sub.6 alkyl optionally substituted with 1 to 3 substituents selected from halogen, CN, C.sub.3-C.sub.6-cycloalkyl and C.sub.1-C.sub.6-alkoxy; R.sup.4 is a monocyclic heterocycle selected from the group consisting of a 5-membered heteroaryl and a 6-membered heteroaryl each of which containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, and each of which is optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, hydroxy, CN, COOH, NO.sub.2, NH.sub.2, SF.sub.5; and in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.6 cycloalkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 cyanoalkoxy, hydroxy-C.sub.1-C.sub.6 alkyl, NH(C.sub.1-C.sub.6 alkyl), NH(C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl), N(C.sub.1-C.sub.6 alkyl).sub.2, N(C.sub.1-C.sub.6 alkyl)(C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl), CO.sub.2C.sub.1-C.sub.6 alkyl, SC.sub.1-C.sub.6 alkylsulfinimidoyl, SC.sub.3-C.sub.6 cycloalkylsulfinimidoyl, SC.sub.2-C.sub.6 alkenylsulfinimidoyl, SC.sub.2-C.sub.6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, SC.sub.1-C.sub.6 alkylsulfonimidoyl, SC.sub.3-C.sub.6 cycloalkylsulfonimidoyl, SC.sub.2-C.sub.6 alkenylsulfonimidoyl, SC.sub.2-C.sub.6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, C(?NOC.sub.1-C.sub.6 alkyl)H, and C(?NOC.sub.1-C.sub.6 alkyl)-C.sub.1-C.sub.6 alkyl; and 3- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein the 3- to 6-membered heterocyclyl substituent may optionally carry 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, hydroxy, CN, COOH, CONH.sub.2, CSNH.sub.2, NO.sub.2, Si(CH.sub.3).sub.3, SF.sub.5, NH.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycanocycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cycloalkyl-C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl, C.sub.1-C.sub.3 cyanoalkylthio, C.sub.1-C.sub.3 cyanoalkylsulfinyl, and C.sub.1-C.sub.3 cyanoalkylsulfonyl; and the following substructures S10-S18, in which the bond to the 5-membered heteroaryl and a 6-membered heteroaryl is marked with a # and Z is CO or CS and Y is independently selected from CO and SO.sub.2: ##STR00103## wherein R.sup.41 is hydrogen or in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, phenyl, heteroaryl and heterocyclyl; R.sup.42 is hydrogen or in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, or C.sub.3-C.sub.6 cycloalkyl; R.sup.43 is independently selected from in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl and phenyl; R.sup.44 is in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, phenyl, heteroaryl and heterocyclyl; 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 unsaturated heterocyclyl which may contain further heteroatoms; R.sup.5 is hydrogen, halogen, CN, NH.sub.2, or in each case optionally substituted C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.3-C.sub.4 halocycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, CO.sub.2(C.sub.1-C.sub.3 alkyl), CH(C.sub.1-C.sub.3 alkoxy).sub.2, CONH(C.sub.1-C.sub.4 alkyl), CON(C.sub.1-C.sub.4 alkyl).sub.2, NHCOC.sub.1C.sub.4 alkyl, N(C.sub.1-C.sub.4 alkyl)COC.sub.1-C.sub.4 alkyl, C(?NOC.sub.1-C.sub.4 alkyl)H, C(?NOC.sub.1-C.sub.4 alkyl)-C.sub.1-C.sub.4 alkyl, NH(C.sub.1-C.sub.3 alkyl), N(C.sub.1-C.sub.3 alkyl).sub.2, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.3-C.sub.6 cycloalkylthio, C.sub.3-C.sub.6 cycloalkylsulfinyl, or C.sub.3-C.sub.6 cycloalkylsulfonyl; and salts and N-oxides thereof.

2. The compound according to claim 1, in which X is O or S; A.sub.1 is N or CR.sup.5; A.sub.2 is N or CR.sup.5; A.sub.3 is N or CR.sup.5; A.sub.4 is N or CR.sup.5; wherein one or two of A.sub.1, A.sub.2, A.sub.3, A.sub.4 represents a nitrogen (N); R.sup.1 is hydrogen; or C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycloalkylC.sub.1-C.sub.6 alkyl, each of which is optionally substituted by a group selected from halogen, CN, C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl and C.sub.1-C.sub.3 alkylsulfonyl; or C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 haloalkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.2-C.sub.6 haloalkynyl; or phenyl-C.sub.1-C.sub.3 alkyl, in which phenyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, CN, NO.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, and C.sub.1-C.sub.3 haloalkylsulfonyl; or heterocyclyl-C.sub.1-C.sub.3 alkyl, wherein the heterocyclyl is selected from the group consisting of saturated and partially unsaturated 3- to 10-membered heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl and the heterocyclyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, CN, NO.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, and C.sub.1-C.sub.3 haloalkylsulfonyl; R.sup.2 is selected from the group consisting of phenyl, pyridine, pyrimidine, pyrazine, pyridazine, thiophene and pyrazole, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, hydroxy, CN, COOH, NO.sub.2, NH.sub.2, SO.sub.2NH.sub.2, SF.sub.5; C.sub.1-C.sub.6 alkyl, optionally substituted with CN, OH or C.sub.3-C.sub.6 cycloalkyl; C.sub.2-C.sub.6 alkenyl, optionally substituted with halogen and CN; C.sub.2-C.sub.6 alkynyl, optionally substituted with halogen and CN; C.sub.3-C.sub.6 cycloalkyl, optionally substituted with halogen, CN, C.sub.1-C.sub.3 alkyl or C.sub.1-C.sub.3 haloalkyl; C.sub.1-C.sub.6 haloalkyl, optionally substituted with CN or C.sub.1-C.sub.6 alkoxy; C.sub.1-C.sub.6 alkoxy, optionally substituted with CN; C.sub.3-C.sub.6 cycloalkoxy, optionally substituted with halogen or CN; C.sub.1-C.sub.6 haloalkoxy, CO.sub.2C.sub.1-C.sub.6 alkyl, NH(C.sub.1-C.sub.6 alkyl), N(C.sub.1-C.sub.6 alkyl).sub.2, SC.sub.1-C.sub.6 alkylsulfinimidoyl, SC.sub.3-C.sub.6 cycloalkylsulfinimidoyl, SC.sub.2-C.sub.6 alkenylsulfinimidoyl, SC.sub.2-C.sub.6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, SC.sub.1-C.sub.6 alkylsulfonimidoyl, SC.sub.3-C.sub.6 cycloalkylsulfonimidoyl, SC.sub.2-C.sub.6 alkenylsulfonimidoyl, SC.sub.2-C.sub.6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, C(?NOC.sub.1-C.sub.6 alkyl)H, C(?NOC.sub.1-C.sub.6 alkyl)-C.sub.1-C.sub.6 alkyl, and (C.sub.1-C.sub.6 alkyl).sub.3-silyl; and the substructures S1-S9, in which the bond to phenyl, pyridine, pyrimidine, pyrazine, pyridazine, thiophene and pyrazole is marked with a # and Z is CO or CS and Y is independently selected from CO and SO.sub.2; ##STR00104## wherein R.sup.21 is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, phenyl, heteroaryl, or heterocyclyl in which phenyl, heteroaryl and heterocyclyl are optionally substituted with 1 to 3 substituents, each independently selected from the group consisting of halogen, CN, NO.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, and C.sub.1-C.sub.3 haloalkylsulfonyl; R.sup.22 is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, or C.sub.3-C.sub.6 cycloalkyl; R.sup.23 is independently selected from in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl and phenyl; R.sup.24 is C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 cyanoalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, phenyl, heteroaryl and heterocyclyl in which phenyl, heteroaryl and heterocyclyl are optionally substituted with 1 to 3 substituents, each independently selected from the group consisting of halogen, CN, NO.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl; or R.sup.21 and R.sup.22 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic 3- to 12-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms, and each of the monocyclic or polycyclic 3- to 12-membered saturated or unsaturated heterocyclyl is optionally substituted with 1 to 4 substituents, each independently selected from the group consisting of halogen, CN, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, and C.sub.1-C.sub.3 haloalkylsulfonyl; and 3- to 6-membered heterocyclyl or a 5- to 6-membered heteroaryl each containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein the 3- to 6-membered heterocyclyl or the 5- to 6-membered heteroaryl substituent may optionally carry 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, hydroxy, CN, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycanocycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cycloalkyl-C.sub.1-C.sub.6 alkyl, C.sub.1C.sub.3 haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl, C.sub.1-C.sub.3 cyanoalkylthio, C.sub.1-C.sub.3 cyanoalkylsulfinyl, and C.sub.1-C.sub.3 cyanoalkylsulfonyl; R.sup.3 is hydrogen or C.sub.1-C.sub.6 alkyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, CN, C.sub.3-C.sub.6-cycloalkyl and C.sub.1-C.sub.6-alkoxy; R.sup.4 is a monocyclic heterocycle selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine and thiazole, each of which is optionally substituted by 1 or 2 substituents independently selected from the group consisting of halogen, hydroxy, CN, COOH, NO.sub.2, NH.sub.2, SF.sub.5; C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 cyanoalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.6 cycloalkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.1-C.sub.6 cyanoalkoxy, hydroxy-C.sub.1-C.sub.6 alkyl, NH(C.sub.1-C.sub.6 alkyl), NH(C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl), N(C.sub.1-C.sub.6 alkyl).sub.2, N(C.sub.1-C.sub.6 alkyl)(C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl), CO.sub.2C.sub.1-C.sub.6 alkyl, SC.sub.1-C.sub.6 alkylsulfinimidoyl, SC.sub.3-C.sub.6 cycloalkylsulfinimidoyl, SC.sub.2-C.sub.6 alkenylsulfinimidoyl, SC.sub.2-C.sub.6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, SC.sub.1-C.sub.6 alkylsulfonimidoyl, SC.sub.3-C.sub.6 cycloalkylsulfonimidoyl, SC.sub.2-C.sub.6 alkenylsulfonimidoyl, SC.sub.2-C.sub.6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, and C(?NOC.sub.1-C.sub.6 alkyl)H, C(?NOC.sub.1-C.sub.6 alkyl)-C.sub.1-C.sub.6 alkyl; and the following substructures S10-S18, in which the bond to the 5-membered heteroaryl and a 6-membered heteroaryl is marked with a # and Z is CO or CS and Y is independently selected from CO and SO.sub.2: ##STR00105## wherein R.sup.41 is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, phenyl, heteroaryl or heterocyclyl in which phenyl, heteroaryl and heterocyclyl are optionally substituted with 1 to 3 substituents, each independently selected from the group consisting of halogen, CN, NO.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, and C.sub.1-C.sub.3 haloalkylsulfonyl; R.sup.42 is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 cyanoalkyl, C.sub.1-C.sub.6 alkyl-C.sub.3-C.sub.6 cycloalkyl, or C.sub.3-C.sub.6 cycloalkyl; R.sup.43 is independently selected from in each case optionally substituted C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl and phenyl; R.sup.44 is C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 cyanoalkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, phenyl, heteroaryl, or heterocyclyl in which phenyl, heteroaryl and heterocyclyl are optionally substituted with 1 to 3 substituents, each independently selected from the group consisting of halogen, CN, NO.sub.2, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, and C.sub.1-C.sub.3 haloalkylsulfonyl; or R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic 3- to 12-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms, and each of the monocyclic or polycyclic 3- to 12-membered saturated or unsaturated heterocyclyl is optionally substituted with 1 to 4 substituents, each independently selected from the group consisting of halogen, CN, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, and C.sub.1-C.sub.3 haloalkylsulfonyl; R.sup.5 is hydrogen, halogen, CN, NH.sub.2, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.3-C.sub.4 halocycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, NH(C.sub.1-C.sub.3 alkyl), N(C.sub.1-C.sub.3 alkyl).sub.2, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.3-C.sub.6 cycloalkylthio, C.sub.3-C.sub.6 cycloalkylsulfinyl, or C.sub.3-C.sub.6 cycloalkylsulfonyl; and salts and N-oxides thereof.

3. The compound according to claim 1, in which X is O or S; A.sub.1 is N; A.sub.2 is N or CR.sup.5; A.sub.3 is N or CR.sup.5; A.sub.4 is N or CR.sup.5; or A.sub.1 is N or CR.sup.5; A.sub.2 is N; A.sub.3 is N or CR.sup.5; A.sub.4 is N or CR.sup.5; or A.sub.1 is N or CR.sup.5; A.sub.2 is N or CR.sup.5; A.sub.3 is N; A4 is N or CR.sup.5; or A.sub.1 is N or CR.sup.5; A.sub.2 is N or CR.sup.5; A.sub.3 is N or CR.sup.5; A4 is N; or A.sub.1 is N; A.sub.2 is N or CR.sup.5; A.sub.3 is N or CR.sup.5; A.sub.4 is N; R.sup.1 is hydrogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.3-C.sub.6 cycloalkylC.sub.1-C.sub.3 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.3 alkoxyC.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkylthioC.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.3 alkylsulfinylC.sub.1-C.sub.3 alkyl, or C.sub.1-C.sub.3 alkylsulfonylC.sub.1-C.sub.3 alkyl; R.sup.2 is selected from the group consisting of phenyl, pyridine, pyrimidine, pyrazine, pyridazine and pyrazole, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, hydroxy, CN, COOH, CONH.sub.2, NO.sub.2, NH.sub.2, SO.sub.2NH.sub.2, SF.sub.5, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.3-C.sub.6 cycloalkylsulfanyl, C.sub.3-C.sub.6 cycloalkylsulfinyl, C.sub.3-C.sub.6 cycloalkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl, C.sub.1-C.sub.3 cyanoalkoxy, hydroxy-C.sub.1-C.sub.4 alkyl, NH(C.sub.1-C.sub.4 alkyl), N(C.sub.1-C.sub.4 alkyl).sub.2, NHCOC.sub.1-C.sub.4 alkyl, NHCOC.sub.3-C.sub.6 cycloalkyl, NHSO.sub.2(C.sub.1-C.sub.4 alkyl), N(C.sub.1-C.sub.4 alkyl)COC.sub.1-C.sub.4 alkyl, N(C.sub.1-C.sub.4 alkyl)COC.sub.3-C.sub.6 cyclolkyl, N(C.sub.1-C.sub.4 alkyl)SO.sub.2C.sub.1-C.sub.4 alkyl, N(SO.sub.2C.sub.1-C.sub.4 alkyl).sub.2, CO.sub.2C.sub.1-C.sub.4 alkyl, CONH(C.sub.1-C.sub.4 alkyl), CONH(C.sub.3-C.sub.6 cycloalkyl), CONH-phenyl, CON(C.sub.1-C.sub.4 alkyl).sub.2, CON(C.sub.1-C.sub.4 alkyl)(C.sub.3-C.sub.6 cycloalkyl), CON(C.sub.1-C.sub.4 alkyl)-phenyl, C(?NOC.sub.1-C.sub.4 alkyl)H, C(?NOC.sub.1-C.sub.4 alkyl)-C.sub.1-C.sub.4 alkyl, (C.sub.1-C.sub.4 alkyl).sub.3-silyl, SO.sub.2NH(C.sub.1-C.sub.4 alkyl), phenylsulfonyl, and 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.4 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 alkoxy and C.sub.1-C.sub.3 haloalkoxy; R.sup.3 is hydrogen, C.sub.1-C.sub.6 alkyl, optionally substituted with 1 to 3 substituents selected from halogen, C.sub.3-C.sub.6-cycloalkyl, or C.sub.1-C.sub.6-alkoxy; R.sup.4 is selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine and thiazole, each of which is optionally substituted by 1 or 2 substituents independently selected from the group consisting of halogen, CN, COOH, NO.sub.2, NH.sub.2, SF.sub.5, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 alkyl-C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, and CO.sub.2C.sub.1-C.sub.6 alkyl, or R.sup.4 is selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine and thiazole, each of which is optionally substituted by 1 substituent selected from the group consisting of halogen, CN, COOH, NO.sub.2, NH.sub.2, SF.sub.5, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.4 alkyl-C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkoxy, and CO.sub.2C.sub.1-C.sub.6 alkyl; and each of which is furthermore substituted by 1 substituent selected from the group consisting of following substructures S10-S18, in which the bond to the aforementioned pyridine, pyrimidine, pyrazine, pyridazine and thiazole is marked with a # and Z is CO or CS and Y is independently selected from CO and SO.sub.2: ##STR00106## wherein R.sup.41 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, or C.sub.1-C.sub.3 alkyl-C.sub.3-C.sub.6 cycloalkyl; R.sup.42 is hydrogen, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.3 cyanoalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.3-C.sub.6 cycloalkyl, or C.sub.1-C.sub.3 alkyl-C.sub.3-C.sub.6 cycloalkyl; R.sup.43 is C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.3 haloalkyl, or C.sub.3-C.sub.6 cycloalkyl; R.sup.44 is C.sub.1-C.sub.4 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.3 haloalkyl, or C.sub.3-C.sub.6 cycloalkyl; or R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic 5 to 6-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms, and each of the monocyclic or polycyclic to 6-membered saturated or unsaturated heterocyclyl is optionally substituted with 1 to 4 substituents, each independently selected from the group consisting of halogen, CN, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, and C.sub.1-C.sub.3 haloalkylsulfonyl; R.sup.5 is hydrogen, halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.3-haloalkyl, C.sub.3-C.sub.4-cycloalkyl, C.sub.1-C.sub.3 alkoxy, or C.sub.1-C.sub.3 haloalkoxy; and salts and N-oxides thereof.

4. The compound according to claim 1, in which X is O or S; A.sub.1 is N; A.sub.2 is N or CR.sup.5; A.sub.3 is N or CR.sup.5; A.sub.4 is N or CR.sup.5; or A.sub.1 is N or CR.sup.5; A.sub.2 is N; A.sub.3 is N or CR.sup.5; A.sub.4 is N or CR.sup.5; or A.sub.1 is N or CR.sup.5; A.sub.2 is N or CR.sup.5; A.sub.3 is N; A4 is N or CR.sup.5; or A.sub.1 is N or CR.sup.5; A.sub.2 is N or CR.sup.5; A.sub.3 is N or CR.sup.5; A4 is N; or A.sub.1 is N; A.sub.2 is N or CR.sup.5; A.sub.3 is N or CR.sup.5; A4 is N; R.sup.1 is hydrogen, methyl, ethyl, cyclopropylmethyl, methoxymethyl, ethoxymethyl, methoxyethyl, methylthioethyl, methylsulfinylethyl or methylsulfonylethyl; R.sup.2 is selected from substructure Q1, Q2 and Q3, in which the bond to the C?X-group is marked with a #: ##STR00107## wherein R.sup.25 is hydroxy, CN, NH.sub.2, SO.sub.2NH.sub.2, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 cyanoalkyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 halocycloalkyl, C.sub.3-C.sub.6 cyanocycloalkyl, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.3-C.sub.6 cycloalkylsulfanyl, C.sub.3-C.sub.6 cycloalkylsulfinyl, C.sub.3-C.sub.6 cycloalkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl, C.sub.1-C.sub.3 cyanoalkoxy, hydroxy-C.sub.1-C.sub.4 alkyl, NH(C.sub.1-C.sub.4 alkyl), N(C.sub.1-C.sub.4 alkyl).sub.2, NHCOC.sub.1-C.sub.4 alkyl, NHCOC.sub.3-C.sub.6 cycloalkyl, NHSO.sub.2(C.sub.1-C.sub.4 alkyl), N(C.sub.1-C.sub.4 alkyl)COC.sub.1-C.sub.4 alkyl, N(C.sub.1-C.sub.4 alkyl)COC.sub.3-C.sub.6 cyclolkyl, N(C.sub.1-C.sub.4 alkyl)SO.sub.2C.sub.1-C.sub.4 alkyl, N(SO.sub.2C.sub.1-C.sub.4 alkyl).sub.2, CO.sub.2C.sub.1-C.sub.4 alkyl, CONH(C.sub.1-C.sub.4 alkyl), CONH(C.sub.3-C.sub.6 cycloalkyl), CONH-phenyl, CON(C.sub.1-C.sub.4 alkyl).sub.2, CON(C.sub.1-C.sub.4 alkyl)(C.sub.3-C.sub.6 cycloalkyl), CON(C.sub.1-C.sub.4 alkyl)-phenyl, C(?NOC.sub.1-C.sub.4 alkyl)H, C(?NOC.sub.1-C.sub.4 alkyl)-C.sub.1-C.sub.4 alkyl, (C.sub.1-C.sub.4 alkyl).sub.3-silyl, SO.sub.2NH(C.sub.1-C.sub.4 alkyl), 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.4 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.3 alkoxy and C.sub.1-C.sub.3 haloalkoxy; and R.sup.26 is hydrogen, halogen, CN, COOH, CONH.sub.2, NO.sub.2, C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.3 haloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.3 alkylthio, C.sub.1-C.sub.3 alkylsulfinyl, C.sub.1-C.sub.3 alkylsulfonyl, C.sub.1-C.sub.3 haloalkylthio, C.sub.1-C.sub.3 haloalkylsulfinyl, C.sub.1-C.sub.3 haloalkylsulfonyl, C.sub.3-C.sub.6 cycloalkylsulfanyl, C.sub.3-C.sub.6 cycloalkylsulfinyl, C.sub.3-C.sub.6 cycloalkylsulfonyl, C.sub.3-C.sub.6 cycloalkyl, C.sub.1-C.sub.3 cyanoalkyl, or C.sub.3-C.sub.6 cyanocycloalkyl; R.sup.27 is hydrogen, or C.sub.1-C.sub.4 alkyl; R.sup.3 is methyl; R.sup.4 is selected from the group consisting of pyridin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-3-yl and 1,3-thiazol-2-yl, each of which is optionally substituted by one substituent independently selected from the group consisting of fluorine, chlorine, bromine, CN, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, cyclopropyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, difluoroethoxy, methoxycarbonyl, and ethoxycarbonyl; or the following substructures S13, in which the bond to the aforementioned pyridin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-3-yl, and 1,3-thiazol-2-yl is marked with a # and Z is CO: ##STR00108## wherein R.sup.41 is hydrogen, methyl, ethyl, cyclopropylmethyl, cyanomethyl, cyclopropyl, difluoroethyl, or trifluoroethyl; R.sup.42 is hydrogen, methyl, ethyl, cyclopropylmethyl, cyanomethyl, cyclopropyl, difluoroethyl, or trifluoroethyl; or R.sup.41 and R.sup.42 together with the nitrogen atom to which they are attached, represent a morpholine, optionally substituted by one to four methyl; R.sup.5 is hydrogen, fluorine, chlorine, bromine, iodine, CN, methyl, ethyl, isopropyl, difluoromethyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, difluoromethoxy, or trifluoromethoxy; and salts and N-oxides thereof.

5. The compound according to claim 1, in which X is O; A.sub.1 is N; A.sub.2 is CR.sup.5; A.sub.3 is CR.sup.5; A.sub.4 is CR.sup.5; or A.sub.1 is CR.sup.5; A.sub.2 is CR.sup.5; A.sub.3 is N; A.sub.4 is CR.sup.5; or A.sub.1 is CR.sup.5; A.sub.2 is CR.sup.5; A.sub.3 is CR.sup.5; A.sub.4 is N; R.sup.1 is hydrogen; R.sup.2 is selected from the group consisting of 3-chloro-5-(trifluoromethoxy)phenyl, 3-bromo-5-(trifluoromethoxy)phenyl, 3-cyano-5-(trifluoromethoxy)phenyl, 3,5-bis(difluoromethyl)phenyl, 3,5-bis-(trifluoromethyl)phenyl, 3,5-bis(difluoromethoxy)phenyl, 3,5-bis-(trifluoromethoxy)phenyl, 3-(1,1-difluoroethyl)-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyano-5-(1-cyano-1-methyl-ethyl)phenyl, 3-(1-cyano-1-methyl-ethyl)-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyano-5-(1-cyanocyclopropyl)phenyl, 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)phenyl, (3-chloro-5-methylsulfonylphenyl), 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)phenyl, 3,5-bis(difluoromethylsulfonyl)phenyl and 5-(difluoromethyl)-1-methyl-pyrazol-3-yl; R.sup.3 is methyl; R.sup.4 is selected from the group consisting of pyrimidin-2-yl, 5-chloro-pyridin-2-yl, 5-cyano-pyridin-2-yl, 5-methoxycarbonyl-2-pyridyl, 5-(aminocarbonyl)pyridin-2-yl, 5-(methylcarbamoyl)pyridin-2-yl, and 5-(dimethylaminocarbonyl)pyridin-2-yl; R.sup.5 is selected from hydrogen, fluorine and methyl; and salts and N-oxides thereof.

6. The compound according to claim 1, wherein the compound has a structure according to formula (I-a) ##STR00109## in which the structural elements A.sub.1, A.sub.2, A.sub.3, A.sub.4, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X have the meanings given in claim 1.

7. The compound according to claim 1, wherein the compound has a structure according to formula (I-b) ##STR00110## in which the structural elements A.sub.1, A.sub.2, A.sub.3, A.sub.4, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and X have the meanings given in claim 1.

8. The compound of claim 1 selected from the group consisting of: 6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride, 1-[3-(5-chloro-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethanamine; 2,2,2-trifluoroacetic acid, 6-[2-(1-aminoethyl)-7-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride, methyl 6-[2-(1-aminoethyl)imidazo[4,5-b]pyridin-3-yl]pyridine-3-carboxylate hydrochloride, 6-[2-[1-aminoethyl]-6-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride, 6-[2-[1-aminoethyl]-5-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride, 1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethanamine hydrochloride, and 1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine trifluoroacetate.

9. A formulation comprising at least one compound of the formula (I) according to claim 1.

10. The formulation according to claim 9, further comprising at least one extender and/or at least one surface-active substance.

11. The formulation according to claim 9, characterized in that the compound of the formula (I) is in a mixture with at least one further active compound.

12. A method for controlling pests especially-animal-pests to an animal, characterized in that a compound of the formula (I) according to claim 1 is allowed to act on the pests and/or their habitat, wherein methods for treatment of a body of the animal by surgery or therapy and diagnostic methods practised on the animal body are excluded.

13. The method according to claim 12, characterized in that 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.

14-18. (canceled)

19. A method for protecting at least one crop plant from pests, the method comprising contacting the at least one crop plant with a compound of the formula (I) according to claim 1.

20. (canceled)

21. The method of claim 19, wherein protecting the at least one crop plant comprises contacting a seed or germinating plant with a compound of the formula (I) according to claim 1.

22. The method of claim 19, wherein the pests are pests to animals.

23. The method of claim 22, 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.

24. A seed obtained by the method according to claim 21.

25. A method of controlling a disease vector, the method comprising use of a compound of the formula (I) according to claim 1, or salt thereof.

Description

DESCRIPTION OF THE PROCESSES AND INTERMEDIATES

[0604] Compounds of formula (I) may be prepared as illustrated in the following scheme 1 where X is O, R.sup.1 is H and A.sup.1, A.sup.2, A.sup.3, A.sup.4, R.sup.2, R.sup.3, R.sup.4, R.sup.5 are as previously defined, PG is an amino protection group, Hal is fluorine, chlorine, bromine or iodine and Q.sup.1, Q.sup.2 are hydroxy or chlorine.

##STR00019##

[0605] As indicated in Scheme 1 the introduction of the heterocyclic amine group can be carried out by an aromatic nucleophilic substitution of an halogen in nitro-azines (1) by heterocyclic amines (2) in different solvents like acetonitrile, DMF, dioxane or THF in the presence of a base like Cs.sub.2CO.sub.3 or Pyridine. Alternatively, the heterocyclic amine can be introduced by Buchwald reaction conditions using different palladium catalysts and suitable ligands, e.g. described in US2010/29638 A1 or WO2012/41476 A1. In a subsequent reaction, the reduction of the nitro group can be achieved by different reduction methods using likewise hydrogen/Pd-C, SnCl.sub.2 dihydrate or iron/NH.sub.4Cl, following methods known in the art. The obtained amine derivatives (4) react further with Boc-protected amino acids or the respective acid chlorides (5 Q.sup.1=OH or Cl) to provide the corresponding amides (6) using conventional couplings reagents, like HATU/DIPEA or alternatively, converting first the amino acid (5 Q.sup.1=OH) into the corresponding reactive mixed acid anhydride, e.g. with chloroformate and N-methyl morpholine. Intermediates (6) are cyclized under acidic conditions and high temperature, e.g. boiling in acetic acid, to provide annulated imidazole intermediates (7). In case of enantiopure amino acids as starting material, a partially racemization might occur during the cyclization. The Boc protection group can be removed under acidic conditions, e.g. HCl in dioxane or trifluoro acetic acid, to obtain annulated imidazolyl alkylamines or the respective salts (8). Finally, intermediates (8) react further with substituted benzoic acids or with the corresponding acid chlorides to provide final products IA.

[0606] Q.sup.2=OH: An imidazole compound of formula (8) is reacted with a carboxylic acid of formula (9) (Q.sup.2=OH) to form compounds of formula IA. For example, a mixture of an imidazole of formula (8), a carboxylic acid of formula (9) (Q.sup.2=OH), a suitable coupling reagent, such as T3P?, HATU or DCC/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 IA which may then be isolated and, if necessary and desired, purified using techniques well known in the art, such as chromatography.

[0607] Q.sup.2=Cl: An imidazole compound of formula (8) is reacted with a carboxylic acid chloride of formula (9) (Q.sup.2=Cl) to form compounds of formula IA. For example, a mixture of an imidazole of formula (8), a carboxylic acid chloride of formula (9) (Q.sup.2=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 IA which may then be isolated and, if necessary and desired, purified using techniques well known in the art, such as chromatography.

[0608] Thioamides of formula (I) (in which X?S) can be obtained by treatment of compounds of formula (IA) with Lawesson's reagent in boiling toluene as described for example in WO 2005009435.

[0609] Carboxylic acids of formula (9) (Q.sup.2=OH) and carboxylic acid chlorides of formula (9) (Q.sup.2=Cl) are commercially available or may be synthesized by methods known to a person skilled in the state of the art.

[0610] More specifically, the synthesis of the amine intermediate INT-1 is described in scheme 1a.

[0611] As indicated in Scheme 1a, starting material (1a) reacts with 6-aminopyridine-3-carbonitrile in DMA at 80? C. in the presence of Cs.sub.2CO.sub.3 as a base. The nitro group is reduced in the next step with SnCl.sub.2 dihydrate. The formation of amide succeeds from a min (4a) and (S)-Boc-Ala using HATU as a coupling reagent and DIPEA as base. The obtained amide (6a) is cyclized under acidic conditions to provide Boc-protected amine intermediate (7a), subsequently deprotected with HCl 4N in dioxane at room temperature to obtain amine hydrochloride (INT-1) which is further derivatized. In case of partially racemization, chiral separation methods known in the art are applied to isolate the pure (S)-enantiomer of 6a,7a or INT-1.

##STR00020##

[0612] Compounds of formula (I) may be prepared as illustrated in the following scheme 2 where X is O, R.sup.1 is H and A.sup.1, A.sup.2, A.sup.3, A.sup.4, R.sup.2, R.sup.3, R.sup.4, R.sup.5 are as previously defined, PG is an amino protection group, Hal is fluorine, chlorine, bromine or iodine and Q.sup.1, Q.sup.2 are hydroxy or chlorine.

##STR00021##

[0613] As indicated in Scheme 2 the introduction of the heterocyclic amine group can be carried out by an aromatic nucleophilic substitution of a halogen in heterocyclic halides (11) by amino-nitro-azines (10) in different solvents like acetonitrile, DMF, dioxane or THF in the presence of a base like Cs.sub.2CO.sub.3 or pyridine. Alternatively, the heterocyclic amine can be introduced by Buchwald reaction conditions using different palladium catalysts and suitable ligands, e.g. described in US2010/29638 A1 or WO2012/41476 A1. The subsequent transformations to compounds of formula (IA) can be performed as already described in scheme 1.

[0614] Optionally, further derivatisations might be possible, e.g. methyl- or ethylester functions in R.sup.4 can be converted into amides CONR.sup.41R.sup.42 by methods known to the skilled artisan, where R.sup.41 and R.sup.42 are as previously defined.

Preparation Examples

Intermediates

6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride (INT-1)

Step 1: Synthesis of 6-[(3-nitropyridin-2-yl)amino]nicotinonitrile

[0615] ##STR00022##

[0616] To a stirred solution of 6-aminopyridine-3-carbonitrile (7.11 g, 59.67 mmol) and Cs.sub.2CO.sub.3 (35.35 g, 108.49 mmol) in 150 ml DMA was added a solution of 2-chloro-3-nitropyridine (8.60 g, 54.24 mmol) in 80 ml DMA dropwise and the reaction mixture was stirred at 80? C. overnight. The mixture was allowed to cool down to room temperature. The reaction was quenched with ice water at room temperature. The resulting mixture was extracted with EtOAc several times. The combined organic layers were washed with H.sub.2O and dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with cyclohexane/EtOAc (2:1) to afford the desired product (5.60 g, 35.7%).

[0617] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO, peak list): ?=10.6624 (9.4); 8.7054 (7.9); 8.7011 (16.0); 8.6938 (15.8); 8.6896 (8.9); 8.6107 (7.8); 8.6065 (7.6); 8.5900 (8.3); 8.5858 (7.6); 8.5785 (0.5); 8.5558 (0.3); 8.2566 (6.1); 8.2509 (5.9); 8.2430 (0.4); 8.2346 (9.9); 8.2289 (9.8); 8.1653 (12.2); 8.1447 (6.8); 8.1432 (7.5); 7.3306 (8.8); 7.3190 (8.5); 7.3099 (8.4); 7.2983 (8.4); 5.7578 (0.7); 4.0562 (1.1); 4.0384 (3.2); 4.0206 (3.3); 4.0028 (1.1); 3.3300 (57.6); 2.6775 (0.4); 2.6729 (0.6); 2.6684 (0.4); 2.5265 (1.4); 2.5218 (2.0); 2.5130 (28.0); 2.5085 (59.2); 2.5040 (79.6); 2.4995 (56.6); 2.4950 (26.3); 2.3354 (0.4); 2.3308 (0.5); 2.3263 (0.4); 1.9900 (14.4); 1.3971 (3.5); 1.1935 (3.8); 1.1757 (7.7); 1.1579 (3.7); ?0.0002 (4.5)

[0618] ESI mass [m/z]: 241.9 [M+H].sup.+

Step 2: 6-[(3-aminopyridin-2-yl)amino]nicotinonitrile

[0619] ##STR00023##

[0620] To a stirred solution of 6-[(3-nitropyridin-2-yl)amino]nicotinonitrile (1.25 g, 5.19 mmol) in 20 ml ethyl acetate was added tin chloride dihydrate (5.86 g, 25.90 mmol) and the reaction mixture was stirred at 70? C. for 1 h. When the mixture was cooled down to room temperature the reaction was quenched with water and basified to pH 9-10 with an aqueous solution of sodium carbonate. The mixture was extracted several times with ethyl acetate. The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4. After filtration the filtrate was concentrated under reduced pressure. The crude was used in the next step without further purification (1.0 g, 72.7% purity, yield: 66%).

[0621] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO, peak list): ?=9.2833 (0.4); 9.2385 (11.2); 9.0450 (0.6); 8.6368 (0.3); 8.6270 (1.1); 8.6221 (1.2); 8.6090 (0.7); 8.6016 (8.4); 8.5999 (9.5); 8.5960 (9.7); 8.5941 (9.4); 8.5820 (0.3); 8.5689 (0.4); 8.3828 (0.7); 8.1775 (0.5); 8.1430 (0.7); 8.1367 (0.8); 8.1333 (0.6); 8.1252 (0.4); 8.0504 (0.4); 8.0447 (0.5); 8.0280 (0.7); 8.0223 (0.8); 8.0149 (0.3); 7.9948 (7.2); 7.9889 (7.2); 7.9724 (9.3); 7.9665 (9.5); 7.9304 (0.7); 7.9081 (0.6); 7.8491 (12.1); 7.8268 (8.7); 7.6360 (7.7); 7.6323 (8.5); 7.6244 (7.9); 7.6206 (8.4); 7.4959 (0.3); 7.4761 (0.4); 7.2761 (0.6); 7.2722 (0.6); 7.2637 (0.6); 7.2598 (0.6); 7.2342 (0.4); 7.2128 (0.4); 7.0990 (0.4); 7.0762 (7.6); 7.0723 (8.4); 7.0567 (9.6); 7.0528 (9.9); 6.9059 (8.3); 6.8942 (7.9); 6.8864 (6.8); 6.8747 (6.4); 6.6969 (0.5); 6.6930 (0.5); 6.6783 (0.6); 6.6744 (0.6); 6.3806 (0.6); 6.3682 (0.6); 6.3621 (0.6); 6.3496 (0.5); 5.3611 (1.1); 5.3242 (16.0); 5.2441 (0.6); 4.6521 (0.4); 4.0575 (0.6); 4.0397 (1.7); 4.0219 (1.7); 4.0042 (0.6); 3.3470 (14.4); 2.5301 (0.4); 2.5255 (0.6); 2.5165 (7.0); 2.5122 (15.4); 2.5077 (21.3); 2.5033 (15.9); 1.9920 (7.4); 1.3021 (0.4); 1.2595 (0.6); 1.2280 (1.2); 1.1942 (2.5); 1.1764 (4.4); 1.1586 (2.2); ?0.0002 (5.4)

[0622] ESI mass [m/z]: 212.2 [M+H].sup.+

Step 3: tert-butyl [(2S)-1-({2-[(5-cyanopyridin-2-yl)amino]pyridin-3-yl}amino)-1-oxopropan-2-yl]carbamate

[0623] ##STR00024##

[0624] A mixture of (2S)-2-[(tert-butoxycarbonyl)amino]propanoic acid (806.20 mg, 4.26 mmol), N,N-diisopropylethylamine (2.17 ml, 12.78 mmol), HATU (1.94 g, 5.11 mmol) in 3 ml DMF was stirred at room temperature for 10 minutes and then 6-[(3-aminopyridin-2-yl)amino]nicotinonitrile (900.0 mg, 4.26 mmol) was added and the reaction was stirred at room temperature overnight. The mixture was purified directly by preparative HPLC to yield the desired product (1.15 g, 65%).

[0625] .sup.1H-NMR (400.2 MHz, d.sub.6-DMSO, peak list): ?=9.8273 (1.1); 9.4949 (0.8); 8.6284 (2.1); 8.6263 (2.1); 8.1999 (1.2); 8.1886 (1.3); 8.0893 (0.9); 8.0676 (1.1); 7.9605 (1.1); 7.9408 (1.2); 7.8617 (0.8); 7.8398 (0.7); 7.2510 (0.7); 7.2371 (0.7); 7.1922 (0.7); 7.1797 (0.8); 7.1746 (0.8); 7.1610 (0.6); 5.7590 (2.2); 4.1516 (0.5); 4.1352 (0.7); 4.1183 (0.5); 3.6981 (0.6); 2.5057 (34.9); 2.5027 (35.1); 1.3945 (0.9); 1.3699 (16.0); 1.3281 (0.7); 1.2840 (3.8); 1.2664 (3.7); 0.0024 (5.8); ?0.0002 (6.5)

[0626] ESI mass [m/z]: 383.5 [M+H].sup.+

Step 4: tert-butyl {(1S)-1-[3-(5-cyanopyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl]ethyl}carbamate

[0627] ##STR00025##

[0628] To a stirred mixture of tert-butyl [(2S)-1-({2-[(5-cyanopyridin-2-yl)amino]pyridin-3-yl}amino)-1-oxopropan-2-yl]carbamate (10.00 g, 26.11 mmol) in dioxane (150.00 mL) was added AcOH (40.00 mL) and the mixture was stirred for 4 days at 100? C. The mixture was basified to pH 8 with saturated NaHCO.sub.3 (aq.). The resulting mixture was extracted with EtOAc several times, the combined organic layers were washed with brine and dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with petroleum ether/EtOAc (3:1), then purified by prep-HPLC to afford a mixture of both enantiomers. This partially racemate was purified by prep-SFC to afford tert-butyl {(1S)-1-[3-(5-cyanopyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl]ethyl}carbamate (1.59 g, 4.37 mmol, 16.71%).

[0629] ESI mass [m/z]: 365.2 [M+H].sup.+

Step 5: 6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile Hydrochloride (INT-1)

[0630] ##STR00026##

tert-Butyl N-[(1S)-1-[3-(5-cyano-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethyl]carbamate (200 mg, 0.54 mmol) was dissolved in 4 mL dioxane and 4 M HCl in dioxane (1.37 mL) was added. The reaction mixture was stirred at room temperature over night. The solvent was evaporated and the remaining residue was used as such in the next step.

[0631] ESI mass [m/z]: 265.2 [amine+H].sup.+

Methyl 6-[2-(1-aminoethyl)-3H-imidazo[4,5-b]pyridin-3-yl]nicotinate Hydrochloride (INT-5)

Step 1: methyl 6-[(3-nitropyridin-2-yl)amino]nicotinate

[0632] ##STR00027##

[0633] To a solution of 5.1 g (33.3 mmol) methyl 6-aminonicotinate and 20.5 g (62.8 mmol) cesium carbonate in 80 ml acetonitrile were added 4.1 g (26.1 mmol) of 2-chloro-3-nitropyridine dropwise and the mixture was stirred at 80? C. overnight. After cooling to room temperature, the mixture was treated with ice water and extracted with ethyl acetate several times. The combined organic layers were washed with water, dried over anhydrous Na.sub.2SO.sub.4 and after filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with cyclohexane/ethyl acetate to afford 780 mg (10.2%) of the title compound.

[0634] .sup.1H-NMR (400.2 MHz, CD.sub.3CN, peaklist): ?=10.5963 (0.8); 8.8964 (2.0); 8.8913 (2.1); 8.6382 (1.7); 8.6297 (3.8); 8.6074 (3.2); 8.3169 (1.4); 8.3113 (1.4); 8.2948 (1.2); 8.2892 (1.2); 7.1545 (1.4); 7.1430 (1.4); 7.1338 (1.4); 7.1222 (1.4); 3.8870 (16.0); 2.1768 (32.9); 2.1643 (0.5); 1.9547 (2.2); 1.9487 (4.3); 1.9426 (6.2); 1.9365 (4.3); 1.9304 (2.2); ?0.0002 (2.8)

[0635] ESI mass [m/z]: 275.3 [M+H].sup.+

Step 2: methyl 6-[(3-aminopyridin-2-yl)amino]nicotinate

[0636] ##STR00028##

[0637] 728.0 mg (2.66 mmol) methyl 6-[(3-nitropyridin-2-yl)amino]nicotinate were solved in 13 ml ethyl acetate and then 3.0 g (13.3 mmol) tinn chloride dihydrate were added and the reaction mixture was stirred 1.5 h at 70? C. After cooling to room temperature, the mixture was diluted with ethyl acetate and basified to pH 9-10 with sat. Na.sub.2CO.sub.3 (aq.). The aqueous phase was extracted with ethyl acetate several times and the combined organic layers were washed with brine, dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was concentrated under reduced pressure and the crude was used in the next step without further purification (645 mg, 94% yield).

[0638] .sup.1H-NMR (400.2 MHz, d6-DMSO, peaklist): ?=9.0965 (3.0); 8.7376 (2.6); 8.7332 (2.4); 8.7318 (2.7); 8.1034 (1.4); 8.0976 (1.4); 8.0810 (1.8); 8.0752 (1.8); 7.9141 (3.0); 7.8918 (2.4); 7.6317 (1.9); 7.6294 (1.8); 7.6200 (1.9); 7.6176 (1.8); 7.0557 (1.7); 7.0534 (1.7); 7.0363 (2.1); 7.0339 (2.0); 6.8727 (1.7); 6.8609 (1.7); 6.8533 (1.4); 6.8416 (1.4); 5.3151 (4.0); 4.0378 (0.4); 4.0201 (0.4); 3.8258 (16.0); 3.3346 (10.2); 2.5039 (14.4); 2.5003 (11.0); 1.9899 (1.7); 1.1933 (0.4); 1.1920 (0.5); 1.1754 (0.9); 1.1742 (0.9); 1.1577 (0.4); 1.1564 (0.4); ?0.0002 (5.8); ?0.0015 (5.7)

[0639] ESI mass [m/z]: 245.1[M+H].sup.+

Step 3: methyl 6-[(3-{[N-(tert-butoxycarbonyl)alanyl]amino}pyridin-2-yl)amino]nicotinate

[0640] ##STR00029##

[0641] To a solution of 0.33 g (1.74 mmol)N-(tert-butoxycarbonyl)alanine in 17 ml dichloromethane were added 0.92 mL (5.23 mmol) N,N-diisopropylethylamine (DIPEA, H?nig's Base) and 0.80 g (2.1 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium-hexafluorophosphate] (HATU) and the mixture was stirred for 10 min at room temperature. Then 0.64 g (2.62 mmol) methyl 6-[(3-aminopyridin-2-yl)amino]nicotinate were added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with a 5% sodium dihydrogen phosphate (aq.), and extracted with dichloromethane several times. The combined organic layers were washed with saturated NaHCO.sub.3 (aq.) and brine, dried over anhydrous Na.sub.2SO.sub.4 and filtered. The filtrate was concentrated under reduced pressure. The reaction mixture was then directly purified by preparative HPLC (eluted with water/acetonitrile) to afford 497 mg (62.0%) of the title compound.

[0642] .sup.1H-NMR (400.2 MHz, d6-DMSO, peaklist): ?=8.7905 (1.4); 8.7856 (1.4); 8.1732 (1.0); 8.1686 (1.1); 8.1515 (0.9); 8.1465 (0.9); 8.0346 (0.6); 7.8287 (0.5); 7.0894 (0.4); 7.0726 (0.5); 7.0608 (0.4); 5.8359 (0.3); 4.1648 (0.5); 4.1481 (0.7); 4.1308 (0.5); 4.0679 (0.9); 4.0501 (0.9); 3.8569 (15.4); 2.1828 (2.7); 1.9728 (4.0); 1.9657 (0.4); 1.9538 (4.1); 1.9476 (7.9); 1.9415 (11.4); 1.9353 (7.8); 1.9292 (4.0); 1.4053 (16.0); 1.3747 (5.8); 1.3567 (5.6); 1.2215 (1.0); 1.2038 (2.0); 1.1859 (1.0); ?0.0002 (2.4)

[0643] ESI mass [m/z]: 416.3 [M+H].sup.+

Step 5: methyl 6-(2-{1-[(tert-butoxycarbonyl)amino]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinate

[0644] ##STR00030##

[0645] To a solution of 490.0 mg (1.18 mmol) methyl 6-[(3-{[N-(tert-butoxycarbonyl)alanyl]amino}pyridin-2-yl)amino]nicotinate in 8 ml dioxane was added 0.7 ml (11.8 mmol) acetic acid and the reaction mixture was stirred at 100? C. overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with water, basified to pH 8 with saturated NaHCO.sub.3 (aq.). The organic phase was washed with brine, dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was concentrated under reduced pressure and the crude was used in the next step without further purification (450 mg, 93% yield).

[0646] .sup.1H-NMR (400.2 MHz, CD.sub.3CN, peaklist): ?=9.1696 (1.2); 9.1645 (1.2); 8.5775 (1.0); 8.5718 (1.0); 8.5565 (1.1); 8.5507 (1.1); 8.3537 (0.9); 8.3503 (1.0); 8.3417 (1.0); 8.3383 (1.0); 8.0907 (1.2); 8.0871 (1.2); 8.0803 (0.6); 8.0706 (1.3); 8.0671 (1.2); 8.0597 (0.5); 7.3741 (1.0); 7.3620 (1.0); 7.3541 (0.9); 7.3421 (0.9); 4.0677 (0.4); 4.0499 (0.4); 3.9547 (11.7); 3.8410 (0.8); 3.6005 (16.0); 2.1979 (1.1); 2.1832 (75.4); 1.9725 (1.7); 1.9658 (0.4); 1.9538 (6.8); 1.9476 (13.1); 1.9414 (18.6); 1.9352 (12.5); 1.9291 (6.3); 1.5206 (1.4); 1.5038 (1.3); 1.2917 (5.9); 1.2216 (0.6); 1.2039 (1.0); 1.1860 (0.6); ?0.0002 (4.3)

[0647] ESI mass [m/z]: 398.5 [M+H].sup.+

Step 6: methyl 6-[2-(1-aminoethyl)-3H-imidazo[4,5-b]pyridin-3-yl]nicotinate Hydrochloride (INT-4)

[0648] ##STR00031##

[0649] To a solution of 409 mg (1.02 mmol) methyl 6-(2-{1-[(tert-butoxycarbonyl)amino]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinate in 21 mL dioxane were added 5.15 ml (20.5 mmol) HCl 4N in dioxane. The reaction mixture was stirred at room temperature for three days. The solvent was evaporated, and the remaining residue was used as such in the next step (420 mg, 100% yield).

[0650] .sup.1H-NMR (400.2 MHz, d6-DMSO, peaklist): ?=9.1796 (0.8); 9.1741 (0.8); 8.7544 (0.6); 8.7433 (0.6); 8.7018 (0.6); 8.6959 (0.6); 8.6804 (0.7); 8.6746 (0.7); 8.5325 (0.6); 8.5289 (0.7); 8.5205 (0.7); 8.5169 (0.7); 8.4530 (0.9); 8.4318 (0.8); 8.3304 (0.7); 8.3268 (0.7); 8.3103 (0.8); 8.3067 (0.7); 7.5540 (0.6); 7.5421 (0.6); 7.5339 (0.6); 7.5219 (0.6); 3.9584 (5.6); 3.8563 (0.7); 3.7551 (0.4); 3.7107 (0.3); 3.7004 (0.4); 3.6803 (0.5); 3.6707 (0.5); 3.6663 (0.5); 3.6560 (0.5); 3.6503 (0.5); 3.6113 (0.4); 3.5988 (0.4); 3.5820 (0.4); 3.5682 (16.0); 2.5259 (0.8); 2.5211 (1.0); 2.5122 (14.7); 2.5078 (31.5); 2.5033 (42.5); 2.4988 (30.6); 2.4944 (14.6); 1.9097 (0.4); 1.6162 (2.1); 1.5994 (2.1); 1.2341 (0.6); ?0.0002 (10.6); ?0.0085 (0.3)

[0651] ESI mass [m/z]: 298.4 [M+H-HCl]+

1-[1-(5-Chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethanamine Hydrochloride (INT-7)

Step 1: 5-chloro-N-(3-nitro-4-pyridyl)pyridin-2-amine

[0652] ##STR00032##

[0653] To a stirred solution of 5-chloro-2-fluoropyridine (2.27 g, 17.3 mmol) and Cs.sub.2CO.sub.3 (9.37 g, 28.8 mmol) in 30 ml DMA at 80? C. was added a solution of 3-nitropyridine-4-amine (2.00 g, 14.4 mmol) in 30 ml DMA dropwise and the reaction mixture was stirred at 80? C. overnight. The mixture was allowed to cool down to room temperature. The reaction was quenched with ice water at room temperature. The resulting mixture was extracted with EtOAc several times. The combined organic layers were washed with H.sub.2O and dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was concentrated under reduced pressure. The crude was used in the next step without further purification (3.60 g, 88.3% yield).

[0654] ESI mass [m/z]: 251.2 [M+H].sup.+

Step 2: N-(5-chloropyridin-2-yl)pyridine-3,4-diamine

[0655] ##STR00033##

[0656] To a stirred solution of 5-chloro-N-(3-nitro-4-pyridyl)pyridin-2-amine (3.60 g, 14.3 mmol) in 72 ml ethyl acetate was added tin chloride dihydrate (16.2 g, 71.7 mmol) and the reaction mixture was stirred at 70? C. for 1 h. When the mixture was cooled down to room temperature the reaction was quenched with water and basified to pH 9-10 with an aqueous solution of sodium carbonate. The mixture was extracted several times with ethyl acetate. The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4. After filtration the filtrate was concentrated under reduced pressure. The crude was used in the next step without further purification (2.51 g, 69.8% yield).

[0657] ESI mass [m/z]: 221.2 [M+H].sup.+

Step 3: tert-butyl [1-({4-[(5-chloropyridin-2-yl)amino]pyridin-3-yl}amino)-1-oxopropan-2-yl]carbamate

[0658] ##STR00034##

[0659] A mixture of N-(tert-butoxycarbonyl)alanine (2.58 g, 13.7 mmol), N,N-diisopropylethylamine (5.94 ml, 34.1 mmol), HATU (5.19 g, 13.7 mmol) in 30 ml DMF was stirred at room temperature for 10 minutes and then N.sup.4-(5-chloropyridin-2-yl)pyridine-3,4-diamine (2.51 g, 11.4 mmol) was added and the reaction was stirred at room temperature overnight. Saturated NaHCO.sub.3 (aq.) was added and the precipitate was removed by filtration. The filtrate was extracted with EtOAc (3?100 mL), the combined organic layers were dried by the addition of Na.sub.2SO.sub.4, filtered and evaporated under reduced pressure. The crude product was purified directly by preparative HPLC (eluted with water/acetonitrile) to yield the desired product (472 mg, 10.5% yield).

[0660] ESI mass [m/z]: 392.4 [M+H].sup.+

Step 4: tert-butyl {1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl]ethyl}carbamate

[0661] ##STR00035##

[0662] To a stirred mixture of tert-butyl [1-({4-[(5-chloropyridin-2-yl)amino]pyridin-3-yl}amino)-1-oxopropan-2-yl]carbamate (815 mg, 2.08 mmol) in dioxane (20.00 mL) was added AcOH (2.38 mL) and the mixture was stirred for 22 h at 100? C. More dioxane (10.00 mL) and AcOH (2.38 mL) were added and the mixture was stirred for 44 h at 100? C. The mixture was basified to pH 8 with saturated NaHCO.sub.3 (aq.). The resulting mixture was extracted with EtOAc several times, the combined organic layers were washed with brine and dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by purified by preparative HPLC (eluted with water/acetonitrile) to afford 446 mg (46.5% yield) of the title compound.

[0663] ESI mass [m/z]: 374.4 [M+H].sup.+

Step 5:1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethanamine Hydrochloride (INT-7)

[0664] ##STR00036##

[0665] tert-Butyl {1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl]ethyl}carbamate (446 mg, 1.19 mmol) was dissolved in 8 mL dioxane and 4 M HCl in dioxane (5.97 mL) was added. The reaction mixture was stirred at room temperature over night. The precipitate was collected by filtration (240 mg) and used without further purification in the next step.

[0666] ESI mass [m/z]: 274.3 [amine+H].sup.+

[0667] .sup.1H-NMR: see NMR peaklist (Table 2). 1-[1-(5-Chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine trifluoroacetate (INT-8)

Step 1: 5-chloro-N-(2-nitropyridin-3-yl)pyridin-2-amine

[0668] ##STR00037##

[0669] 12.5 g (95.0 mmol) 5-chloro-2-fluoropyridine and 56.3 g (172.8 mmol) cesium carbonate were suspended in 100 ml DMA and the reaction mixture was stirred at 80? C. Then 12.0 g (86.4 mmol) 2-nitropyridin-3-amine dissolved in 100 ml DMA were added dropwise and the mixture was stirred at 80? C. overnight. After cooling to room temperature, the mixture was treated with ice water and extracted with ethyl acetate several times. The combined organic layers were washed with water, dried over anhydrous Na.sub.2SO.sub.4 and after filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with cyclohexane/EtOAc to afford 13.83 g (72.2%) of the title compound.

[0670] .sup.1H-NMR (400.2 MHz, d6-DMSO, peaklist): ?=9.6748 (13.6); 8.4673 (9.4); 8.4637 (10.7); 8.4464 (10.4); 8.4428 (11.1); 8.3187 (0.3); 8.1982 (11.6); 8.1945 (12.3); 8.1874 (12.9); 8.1837 (12.3); 8.1273 (13.6); 8.1207 (13.9); 7.8018 (12.2); 7.7951 (11.6); 7.7797 (12.9); 7.7731 (12.8); 7.7646 (11.2); 7.7538 (10.5); 7.7438 (10.5); 7.7330 (10.1); 7.0951 (16.0); 7.0841 (0.4); 7.0730 (15.0); 3.3849 (0.4); 3.3524 (223.7); 3.3306 (1.0); 2.6774 (0.7); 2.6729 (1.0); 2.6684 (0.7); 2.6640 (0.3); 2.5264 (2.2); 2.5217 (3.4); 2.5129 (53.2); 2.5085 (115.2); 2.5039 (156.8); 2.4994 (111.7); 2.4949 (51.7); 2.3397 (0.3); 2.3354 (0.7); 2.3308 (1.0); 2.3263 (0.7); 2.3218 (0.3); 2.0769 (0.4); ?0.0002 (0.6)

[0671] ESI mass [m/z]: 251.1 [M+H].sup.+

Step 2: N.SUP.3.-(5-chloropyridin-2-yl)pyridine-2,3-diamine

[0672] ##STR00038##

[0673] 10.7 g (42.8 mmol) 5-chloro-N-(2-nitropyridin-3-yl)pyridin-2-amine were dissolved in 200 ml ethyl acetate and then 48.3 g (214.1 mmol) tinn chloride dihydrate were added and the reaction mixture was stirred 1 h at 70? C. After cooling to room temperature, the mixture was treated with water and basified to pH 9-10 with saturated Na.sub.2CO.sub.3 (aq.). The resulting mixture was extracted with EtOAc several times, dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was concentrated under reduced pressure and the crude was used in the next step without further purification (6.13 g, 65% yield).

[0674] .sup.1H-NMR (400.2 MHz, d6-DMSO, peaklist): ?=8.1607 (7.2); 8.0648 (7.2); 8.0583 (7.3); 7.7234 (16.0); 7.7149 (3.7); 7.7107 (7.2); 7.7046 (6.3); 7.7009 (3.1); 7.6080 (5.4); 7.6013 (5.2); 7.5857 (5.7); 7.5790 (5.5); 6.7264 (7.9); 6.7041 (7.6); 6.5794 (5.1); 6.5664 (4.5); 6.5610 (4.7); 6.5480 (4.9); 5.7173 (8.1); 3.3361 (16.7); 2.6718 (0.4); 2.5254 (1.0); 2.5117 (21.7); 2.5074 (45.4); 2.5029 (60.6); 2.4984 (43.0); 2.4940 (19.9); 2.3296 (0.4); 1.9896 (0.8); 1.1748 (0.4); 0.0079 (1.6); ?0.0002 (49.2); ?0.0085 (1.6)

[0675] ESI mass [m/z]: 221.1 [M+H].sup.+

Step 3: tert-butyl [1-({3-[(5-chloropyridin-2-yl)amino]pyridin-2-yl}amino)-1-oxopropan-2-yl]carbamate

[0676] ##STR00039##

[0677] 2.68 g (14.2 mmol)N-(tert-butoxycarbonyl)alanine, 7.2 mL (42.5 mmol) N,N-diisopropylethylamine (DIPEA, H?nig's Base) and 6.45 g (17.0 mmol) [0-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium-hexafluorophosphate] (HATU) dissolved in 30 mL dichloromethane were stirred for 10 min at room temperature. Then 3.12 g (14.18 mmol) N.sup.3-(5-chloropyridin-2-yl)pyridine-2,3-diamine were added and the reaction mixture was stirred at room temperature overnight. After further addition of 3 ml of dimethylformamide the mixture was stirred additionally 4 h at room temperature. Finally, a solution of 1.34 g (7.08 mmol)N-(tert-butoxycarbonyl)alanine, 3.22 g (8.5 mmol) HATU and 3.1 ml DIPEA in dichloromethane stirred previously 10 minutes was added and the mixture was stirred at room temperature overnight. The reaction mixture was treated with water and extracted with dichloromethane several times. The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified first by silica gel column chromatography, eluted with cyclohexane/EtOAc and then then purified by prep-HPLC to afford 978.0 mg (17.0%) of the title compound.

[0678] .sup.1H-NMR (400.2 MHz, d6-DMSO, peaklist): ?=10.2788 (1.0); 8.4417 (0.8); 8.4227 (0.8); 8.1456 (1.3); 8.1397 (1.4); 8.0827 (0.9); 8.0743 (0.9); 8.0333 (1.2); 7.6869 (0.9); 7.6804 (0.9); 7.6647 (1.0); 7.6582 (1.0); 7.3070 (1.3); 7.2954 (1.3); 7.2866 (1.4); 7.2750 (1.9); 7.2621 (0.7); 6.9163 (1.0); 6.8941 (1.0); 4.1486 (0.4); 4.1317 (0.6); 4.1154 (0.4); 3.3175 (15.4); 2.5239 (0.4); 2.5192 (0.7); 2.5106 (9.7); 2.5061 (20.5); 2.5015 (27.5); 2.4969 (19.2); 2.4924 (8.8); 1.3919 (16.0); 1.2698 (3.5); 1.2521 (3.4); ?0.0002 (4.4)

[0679] ESI mass [m/z]: 392.1 [M+H].sup.+

Step 4: tert-butyl {1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethyl}carbamate

[0680] ##STR00040##

[0681] To a solution of 739 g (1.88 mmol) tert-butyl [1-({3-[(5-chloropyridin-2-yl)amino]pyridin-2-yl}amino)-1-oxopropan-2-yl]carbamate in dioxane was added 1 ml acetic acid and the reaction mixture was stirred for two days at 100? C. After evaporation of the mixture under vacuum the crude was used in the next step without further purification (702 mg, 76% yield, 76.5% purity).

[0682] .sup.1H-NMR (400.2 MHz, d6-DMSO, peaklist): ?=12.0060 (0.4); 8.7398 (1.3); 8.7341 (1.3); 8.4797 (1.4); 8.4761 (1.6); 8.4679 (1.5); 8.4643 (1.6); 8.2799 (0.8); 8.2737 (0.8); 8.2582 (0.9); 8.2525 (0.8); 8.2456 (0.6); 7.8147 (1.0); 7.8049 (1.6); 7.7967 (1.1); 7.7838 (1.4); 7.3692 (0.7); 7.3488 (0.8); 7.3113 (1.2); 7.2994 (1.2); 7.2911 (1.2); 7.2792 (1.1); 5.2270 (0.5); 5.2204 (0.4); 5.2018 (0.6); 5.1837 (0.4); 4.9090 (1.1); 4.8399 (0.4); 4.3289 (0.8); 4.3252 (0.4); 4.0010 (0.7); 3.8322 (0.4); 3.8024 (0.5); 3.6092 (0.7); 3.6014 (1.1); 3.5951 (0.6); 3.5900 (0.5); 3.5834 (0.4); 3.5727 (0.5); 3.5669 (0.7); 3.5568 (0.5); 3.5508 (0.6); 3.5460 (0.5); 3.5296 (0.7); 3.5213 (0.8); 3.4993 (0.6); 3.4939 (0.9); 3.4317 (0.3); 3.4276 (0.4); 3.4045 (0.4); 3.3090 (3.6); 3.1705 (0.5); 3.1541 (0.5); 3.1427 (0.4); 3.1261 (0.4); 2.9943 (1.0); 2.8135 (0.5); 2.6908 (2.8); 2.5195 (0.4); 2.5108 (7.7); 2.5064 (16.8); 2.5019 (23.4); 2.4974 (17.2); 2.4931 (8.5); 2.0819 (0.3); 2.0512 (0.6); 1.5027 (2.9); 1.4857 (2.8); 1.3748 (0.6); 1.3654 (2.2); 1.3279 (0.8); 1.2527 (16.0); 1.1257 (0.7); 1.1088 (0.6); 1.0466 (0.8); 1.0314 (0.8); ?0.0002 (1.8)

[0683] ESI mass [m/z]: 374.1 [M+H].sup.+

Step 5: 1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine Trifluoroacetate (INT-8)

[0684] ##STR00041##

[0685] To a solution of 700 mg tert-butyl {1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethyl}carbamate in 25 mL dioxane were added 2.88 ml (37.4 mmol) TFA. The reaction mixture was stirred 3 h at room temperature overnight. The solvent was evaporated, and the remaining residue was used as such in the next step (735 mg, 100% yield).

[0686] .sup.1H-NMR (600.1 MHz, d6-DMSO, peaklist): ?=8.8227 (1.9); 8.8220 (1.9); 8.8184 (2.0); 8.8176 (1.9); 8.7373 (1.4); 8.7313 (1.4); 8.6617 (0.1); 8.6299 (0.1); 8.6251 (0.1); 8.5961 (1.6); 8.5937 (1.7); 8.5883 (1.8); 8.5858 (1.7); 8.4440 (0.1); 8.3713 (1.7); 8.3669 (1.6); 8.3570 (1.8); 8.3526 (1.7); 8.3167 (0.2); 8.2605 (0.2); 8.2498 (0.2); 8.2288 (0.1); 8.2119 (0.1); 8.1415 (0.2); 8.1378 (0.4); 8.1266 (0.2); 8.1222 (0.1); 8.0741 (1.6); 8.0716 (1.7); 8.0604 (1.8); 8.0579 (1.8); 7.9260 (2.2); 7.9252 (2.1); 7.9117 (2.1); 7.9109 (2.0); 7.7110 (0.1); 7.7065 (0.1); 7.6963 (0.1); 7.6917 (0.1); 7.4599 (1.6); 7.4520 (1.6); 7.4462 (1.6); 7.4383 (1.6); 4.9961 (0.2); 4.9873 (0.4); 4.9778 (0.5); 4.9671 (0.4); 4.9570 (0.2); 4.7158 (1.1); 4.5296 (0.1); 4.5224 (0.1); 4.5145 (0.1); 4.3305 (0.1); 4.0693 (0.2); 3.7756 (0.2); 3.7713 (0.1); 3.7681 (0.2); 3.7650 (0.1); 3.7606 (0.1); 3.7139 (0.7); 3.6822 (0.1); 3.6743 (0.1); 3.6664 (0.1); 3.5698 (16.0); 3.3937 (0.1); 3.0159 (1.1); 2.8890 (1.0); 2.6922 (4.5); 2.6205 (0.2); 2.6174 (0.3); 2.6144 (0.2); 2.5564 (0.1); 2.5471 (0.2); 2.5378 (0.2); 2.5264 (0.7); 2.5233 (0.8); 2.5202 (0.8); 2.5115 (14.5); 2.5085 (32.2); 2.5054 (45.2); 2.5023 (32.4); 2.4993 (14.8); 2.3924 (0.2); 2.3893 (0.3); 2.3862 (0.2); 1.9102 (0.3); 1.5564 (5.1); 1.5450 (5.1); 1.5359 (0.5); 1.4161 (0.3); 1.4045 (0.3); 1.3942 (0.2); 1.3822 (0.2); 1.3577 (0.3); 1.3088 (0.5); 1.2973 (0.5); 1.2365 (0.4); 1.1125 (0.2); 1.0446 (0.2); 1.0345 (0.2); 0.0968 (0.3); 0.0054 (2.1); ?0.0001 (72.5); ?0.0057 (2.3); ?0.1003 (0.3)

[0687] ESI mass [m/z]: 274.3 [M+H-TFA].sup.+

Examples

N-[(1S)-1-[3-(5-cyano-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethyl]-3-methylsulfonyl-5-(trifluoromethoxy)benzamide (example I-1)

[0688] ##STR00042##

[0689] To a solution of 35.5 mg (0.13 mmol) 3-(1-cyano-1-methyl-ethyl)-5-(trifluoromethoxy)benzoic acid in 1 mL N,N-dimethylformamide (DMF) were added 0.06 mL (0.33 mmol) N,N-diisopropylethylamine (DIPEA; H?nig's Base) and 86.3 mg (0.22 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium-hexafluorophosphate] (HATU). The mixture was stirred for 10 min at room temperature. Then 39.1 mg (0.13 mmol) 6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride were added and the reaction mixture was stirred at room temperature over night. The reaction mixture was then directly purified by preparative HPLC (eluted with water/acetonitrile) to afford 29.1 mg (41.4% yield) of the title compound.

[0690] ESI mass [m/z]: 520.2 [M+H].sup.+

[0691] .sup.1H-NMR: see NMR peaklist (Table 1).

Methyl 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinate (example I-22)

[0692] ##STR00043##

[0693] To a solution of 485.0 mg (1.45 mmol) methyl 6-[2-(1-aminoethyl)-3H-imidazo[4,5-b]pyridin-3-yl]nicotinate hydrochloride in 10 ml dichloromethane were added 0.61 mL (4.36 mmol) triethylamine and the mixture was stirred 30 minutes at room temperature followed by the addition of 442.0 mg (1.60 mmol) 3,5-bis(trifluoromethyl)benzoyl chloride solved previously in 2 ml of dichloromethane. The reaction mixture was stirred at room temperature overnight. The mixture was washed with 5% sodium dihydrogen phosphate (aq.) and extracted with dichloromethane several times. The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4 and filtered. The filtrate was concentrated under reduced pressure. The crude was suspended in 6 ml of acetonitrile and the corresponding precipitate was filtered and dried while the filtrate was then purified by preparative HPLC (eluted with water/acetonitrile) to afford 288 mg (36.0%) of the title compound.

[0694] ESI mass [m/z]: 538.2 [M+H].sup.+

[0695] .sup.1H-NMR: see NMR peaklist (Table 1).

6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)-N,N-dimethylnicotinamide (example I-26) Step 1: 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinic Acid

[0696] ##STR00044##

[0697] To a solution of 270 mg (0.50 mmol) methyl 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinate (from example I-22) in a mixture of THF/water (6 ml/0.6 ml) were added 42 mg (1.0 mmol) lithium hydroxide and the mixture was stirred at room temperature overnight.

[0698] The mixture was diluted with ethyl acetate and acidified with HCl 10%. The aqueous phase was separated and extracted with ethyl acetate several times. The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4 and after filtration, the filtrate was concentrated under reduced pressure. The crude was used in the next step without further purification to afford 260 mg (82.0%) of the title compound.

[0699] .sup.1H-NMR (400.2 MHz, CD.sub.3CN, peaklist): ?=9.1430 (4.6); 9.1376 (4.8); 8.8535 (0.4); 8.6401 (0.9); 8.5111 (3.1); 8.5054 (3.0); 8.4903 (4.0); 8.4844 (3.4); 8.4396 (0.5); 8.4351 (0.5); 8.4076 (3.3); 8.4045 (3.4); 8.3955 (3.4); 8.3927 (3.5); 8.2350 (1.1); 8.1991 (10.3); 8.1806 (0.7); 8.1666 (0.4); 8.1485 (0.4); 8.1406 (3.3); 8.1374 (3.3); 8.1205 (8.0); 8.0573 (5.6); 8.0364 (5.8); 8.0222 (1.3); 7.9346 (0.7); 7.5910 (0.4); 7.4266 (3.1); 7.4145 (3.1); 7.4065 (3.0); 7.3944 (2.9); 6.9744 (0.8); 6.0060 (0.6); 5.9886 (2.3); 5.9706 (3.4); 5.9526 (2.3); 5.9355 (0.5); 4.0862 (0.5); 4.0679 (1.5); 4.0502 (1.5); 4.0319 (0.5); 3.9236 (0.4); 3.1779 (0.3); 2.9701 (0.3); 2.9638 (0.3); 2.9029 (0.4); 2.8856 (0.4); 2.8600 (0.4); 2.8542 (0.4); 2.8504 (0.4); 2.8003 (0.5); 2.7166 (0.7); 2.6825 (0.8); 2.6260 (1.0); 2.5965 (1.2); 2.5664 (1.4); 2.5415 (1.6); 2.4809 (3.2); 2.4762 (4.2); 2.4717 (5.0); 2.4670 (4.4); 2.4629 (3.7); 2.2422 (43.0); 2.1221 (8.4); 2.1150 (8.3); 2.1089 (8.3); 2.1027 (7.3); 2.0964 (6.3); 2.0526 (4.0); 1.9994 (2.3); 1.9933 (2.2); 1.9728 (8.9); 1.9657 (7.3); 1.9538 (124.1); 1.9477 (207.5); 1.9415 (297.5); 1.9354 (205.2); 1.9292 (106.5); 1.8818 (1.4); 1.8742 (1.4); 1.8369 (1.0); 1.8190 (1.0); 1.8022 (1.1); 1.7826 (1.6); 1.7762 (2.2); 1.7648 (16.0); 1.7476 (15.0); 1.6748 (1.7); 1.6569 (1.6); 1.6204 (0.5); 1.6009 (0.6); 1.5826 (0.6); 1.5701 (0.5); 1.5591 (0.8); 1.5408 (0.8); 1.5038 (1.1); 1.4860 (1.1); 1.4495 (0.4); 1.4322 (0.4); 1.3869 (11.4); 1.3552 (0.5); 1.3402 (1.0); 1.3156 (1.0); 1.2851 (1.8); 1.2699 (5.2); 1.2405 (1.0); 1.2218 (2.4); 1.2164 (2.4); 1.2039 (4.3); 1.2001 (3.4); 1.1863 (2.1); 1.1637 (0.4); 1.1463 (0.4); 1.0830 (0.5); 1.0607 (0.6); 0.8980 (0.5); 0.8818 (1.1); 0.8590 (1.1); 0.8415 (0.8); 0.1462 (1.2); 0.0080 (7.3); ?0.0002 (234.6); ?0.0078 (9.7); ?0.0411 (0.4); ?0.1497 (1.1)

[0700] ESI mass [m/z]: 524.3 [M+H].sup.+

Step 2: 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)-N,N-dimethylnicotinamide (Example I-26)

[0701] ##STR00045##

[0702] To a solution of 60 mg (0.11 mmol) 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinic acid in 2.0 ml dichloromethane were added 0.06 mL (0.32 mmol) N,N-diisopropylethylamine (DIPEA, H?nig's Base) and 52.0 mg (0.14 mmol) [0-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium-hexafluorophosphate] (HATU) and the mixture was stirred for 30 min at room temperature. Then a solution of 0.086 ml (0.17 mmol) dimethylamine 2 M in THF solved previously in 1 ml dichloromethane was added and the reaction mixture was stirred at room temperature overnight. After evaporation of the solvent under pressure the crude was then directly purified by preparative HPLC (eluted with water/acetonitrile) to afford 40 mg (64.0%) of the title compound.

[0703] ESI mass [m/z]: 551.2 [M+H].sup.+

[0704] .sup.1H-NMR: see NMR peaklist (Table 1).

N-[1-[I-(5-chloro-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethyl]-3-cyclopropyl-5-(trifluoromethoxy) benzamide (Example I-33)

[0705] ##STR00046##

[0706] To a solution of 67.0 mg (0.27 mmol) 3-cyclopropyl-5-(trifluoromethoxy)benzoic acid in 2 ml mL N,N-dimethylformamide were added 0.12 mL (0.70 mmol) N,N-diisopropylethylamine (DIPEA, H?nig's Base) and 180.0 mg (0.47 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium-hexafluorophosphate] (HATU) and the mixture was stirred for 10 min at room temperature. Then 104.7 mg (0.27 mmol) 1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine trifluoroacetate were added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then directly purified by preparative HPLC (eluted with water/acetonitrile). The obtained product was dissolved in DCM and filtered through a basic cartridge. The filtrate was evaporate under vacuo to afford 53 mg (38.0%) of the title compound.

[0707] ESI mass [m/z]: 502.2 [M+H].sup.+

[0708] .sup.1H-NMR: see NMR peaklist (Table 1).

N-[1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide

Example I-39

[0709] ##STR00047##

[0710] To a solution of 50.0 mg (0.194 mmol) 3,5-bis(trifluoromethyl)benzoic acid in 2 mL N,N-dimethylformamide (DMF) were added 0.05 mL (0.27 mmol) N,N-diisopropylethylamine (DIPEA; H?nig's Base) and 88.4 mg (0.23 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium-hexafluorophosphate] (HATU). The mixture was stirred for 30 min at room temperature. Then 79.5 mg (0.29 mmol) rac-1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridine-2-yl]ethanamine hydrochloride (INT-7) were added and the reaction mixture was stirred at room temperature over night. Another 50.0 mg (0.194 mmol) 3,5-bis(trifluoromethyl)benzoic acid in 1 mL N,N-dimethylformamide (DMF) were mixed with 0.05 mL (0.27 mmol) N,N-diisopropylethylamine (DIPEA; H?nig's Base) and 88.4 mg (0.23 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N,N-tetramethyluronium-hexafluorophosphate] (HATU), stirred for 30 min at room temperature and added to the reaction mixture. The mixture was stirred for 3 d at room temperature. The reaction mixture was then directly purified by preparative HPLC (eluted with water/acetonitrile) to afford 6.8 mg (6.1% yield) of the title compound.

[0711] ESI mass [m/z]: 514.3 [M+H].sup.+

[0712] .sup.1H-NMR: see NMR peaklist (Table 1).

Analytical Methods

[0713] The analytical methods described below refer to all information in the entire document, unless the procedure of the respective analytical determination is described separately at the respective passage.

Mass Spectrometry

[0714] The determination of [M+H].sup.+ or M.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.

Instruments:

[0715] LC-MS3: Waters UPLC with SQD2 mass spectrometer and SampleManager autosampler. Linear gradient 0.0 to 1.70 minutes from 10% acetonitrile to 95% acetonitrile, from 1.70 to 2.40 minutes constant 95% acetonitrile, flow 0.85 ml/min.

[0716] LC-MS6 and LC-MS7: Agilent 1290 LC, Agilent MSD, HTS PAL autosampler. Linear gradient 0.0 to 1.80 minutes from 10% acetonitrile to 95% acetonitrile, from 1.80 to 2.50 minutes constant 95% acetonitrile, flow 1.0 ml/min.

[0717] The determination of [M+H].sup.+ by LC-MS under neutral chromatographic conditions was done with acetonitrile and Millipore water containing 79 mg/l ammonia carbonate as eluents.

Instruments:

[0718] LC-MS4: Waters IClass Acquity with QDA mass spectrometer and FTN autosampler (column Waters Acquity 1.7 ?m 50 mm*2.1 mm, oven temperature 45? C.). Linear gradient 0.0 to 2.10 minutes from 10% acetonitrile to 95% acetonitrile, from 2.10 to 3.00 minutes constant 95% acetonitrile, flow 0.7 ml/min.

[0719] LC-MS8: Waters IClass Acquity with QDA mass spectrometer and FTN autosampler (column Waters Acquity 1.7 ?m 50 mm*2.1 mm, oven temperature 45? C.). Linear gradient 0.0 to 2.10 minutes from 10% acetonitrile to 95% acetonitrile, from 2.10 to 3.00 minutes constant 95% acetonitrile, flow 0.7 ml/min.

[0720] Retention time indices were calculated in all cases according to a homologues series of straight chain alkan-2-ones with 3 to 16 carbons where the index of the first alkanone was set to 300, the last to 1600, the ones between correspondingly and using linear interpolation between successive alkanones.

NMR

[0721] The determination of .sup.1H-NMR data was done with a Bruker Avance III 400 MHz spectrometer equipped with a 1.7 mm TCI probehead, with tetramethylsilane as reference (0.00 ppm) and the measurements were recorded usually from solutions in the solvents CD.sub.3CN, CDCl.sub.3 or d.sub.6-DMSO. Alternatively, a Bruker Avance III 600 MHz instrument equipped with a 5 mm CPNMP probehead or a Bruker Avance NEO 600 MHz instrument equipped with a 5 mm TCI probehead were used for the measurements. Usually the measurements were carried out with a probehead temperature of 298 K. Other measurement temperatures are explicitly noticed.

[0722] The NMR data of selected examples are listed either in conventional form (? values, multiplet splitting, number of hydrogen atoms) or as NMR peak lists.

NMR Peak Lists Procedure

[0723] .sup.1H-NMR data of selected examples are written in form of .sup.1H-NMR peak lists. ?-Values in ppm and the signal intensity in round brackets are listed to each signal peak. Semicolons are depicted as delimiters between the ?-valuesignal intensity pairs.

[0724] Therefore the peak list of an example has the form:

[00001]${?}_1\left({\mathrm{intensity}}_1\right);{?}_2\left({\mathrm{intensity}}_2\right);.Math.;{?}_i\left({\mathrm{intensity}}_i\right);.Math.;{?}_n\left({\mathrm{intensity}}_n\right)$

[0725] The intensity of sharp signals correlates with the height of the signals in a printed view of a .sup.1H-NMR spectrum in cm and shows the real relations of signal intensities. Several peaks from broad signals or the middle of the signal and their relative intensity in comparison to the most intensive signal in the spectrum can be shown.

[0726] Tetramethylsilane or the chemical shift of the solvent in cases where the sample does not contain tetramethylsilane is used for a calibration of the chemical shift for .sup.1H spectra. Therefore, the tetramethylsilane peak can occur in .sup.1H-NMR peak lists, but not necessarily.

[0727] .sup.1H-NMR peak lists are equivalent to classical .sup.1H-NMR prints and contain usually all peaks, which are also listed at classical .sup.1H-NMR-interpretations.

[0728] In addition, they can show signals of solvents, stereoisomers of the compounds which are optionally object of the invention, and/or peaks of impurities, like classical .sup.1H-NMR prints.

[0729] .sup.1H-NMR solvent signals, the tetramethylsilane signal and the water signal in the corresponding solvent are excluded from the relative intensity calibration as they have very high intensity values.

[0730] On average, the peaks of stereoisomers of the compounds according to the invention and/or peaks of impurities have usually a lower intensity than the peaks of compounds according to the invention (for example with a purity >90%).

[0731] Such stereoisomers and/or impurities can be typical for the specific preparation process. Thus, the corresponding peaks can help to recognize the reproduction of the preparation process via side-products-fingerprints.

[0732] An expert, who calculates the peaks of the target compounds with known methods (MestreC, ACD-simulation, but also with empirically evaluated expectation values), can assign the peaks of the target compounds as needed, optionally using additional intensity filters. This assignment would be similar to the usual peak picking at classical .sup.1H-NMR interpretations.

[0733] The used solvent can be extracted from the JCAMP file with the parameter solvent, the spectrometer frequency with observe frequency and the spectrometer type with spectrometer/data system.

[0734] .sup.13C-NMR data are displayed analogous to .sup.1H-NMR data as peak lists from broadband decoupled .sup.13C-NMR spectra. .sup.13C-NMR solvent signals and tetramethylsilane are excluded from the relative intensity calibration as these signals can have very high intensities.

[0735] Further details of NMR-data description with peak lists are disclosed in the publication Citation of NMR Peaklist Data within Patent Applications of the Research Disclosure Database Number 564025.

[0736] 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 and X is oxygen and which are obtained according to or analogously to the preparation examples described above.

##STR00048##

TABLE-US-00001 TABLE 1 ESI Ex- Mass ample Structure.sup.1) NMR Peak List.sup.2) (m/z).sup.3) I-1 [00049] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.2021 (0.9); 9.1837 (0.9); 9.0596 (1.4); 9.0556 (1.4); 9.0540 (1.4); 8.5575 (1.1); 8.5518 (1.0); 8.5364 (1.2); 8.5307 (1.2); 8.3980 (1.0); 8.3944 (1.2); 8.3860 (1.1); 8.3824 (1.2); 8.2440 (1.1); 8.2405 (1.1); 8.2240 (1.2); 8.2204 (1.1); 8.1271 (1.6); 8.1060 (1.4); 7.8347 (1.0); 7.8310 (1.8); 7.8274 (1.2); 7.6461 (1.2); 7.5876 (1.2); 7.4634 (1.1); 7.4514 (1.0); 7.4434 (1.0); 7.4314 (1.1); 5.8701 (0.6); 5.8525 (0.9); 5.8348 (0.6); 3.3452 (13.2); 2.5272 (0.4); 2.5226 (0.6); 2.5137 (8.1); 2.5093 (17.3); 2.5048 (23.4); 2.5003 (16.9); 2.4959 (8.0); 2.0783 (1.5); 1.7467 (1.1); 1.7201 (3.6); 1.7098 (16.0); 1.7034 (4.5); ?0.0002 (3.7) 520.2 I-2 [00050] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.0557 (7.1); 9.0516 (6.7); 9.0502 (6.5); 9.0243 (4.3); 9.0059 (4.3); 8.5604 (5.2); 8.5547 (4.9); 8.5393 (5.6); 8.5336 (5.4); 8.3888 (5.0); 8.3853 (5.4); 8.3768 (5.4); 8.3733 (5.3); 8.2321 (5.2); 8.2286 (5.1); 8.2121 (5.8); 8.2085 (5.2); 8.1150 (7.2); 8.0939 (6.6); 7.4555 (5.1); 7.4435 (4.9); 7.4355 (4.8); 7.4235 (4.8); 7.3075 (9.2); 7.3037 (9.6); 7.2546 (5.9); 5.8553 (0.6); 5.8380 (2.8); 5.8204 (4.2); 5.8027 (2.8); 5.7855 (0.6); 3.3319 (95.5); 2.6767 (0.8); 2.6721 (1.1); 2.6676 (0.8); 2.5254 (3.5); 2.5118 (68.2); 2.5076 (134.6); 2.5032 (174.2); 2.4987 (122.4); 2.4944 (56.2); 2.3344 (0.8); 2.3300 (1.1); 2.3256 (0.8); 2.0767 (0.9); 2.0365 (0.8); 2.0240 (1.7); 2.0155 (1.9); 2.0032 (3.4); 1.9907 (2.0); 1.9823 (1.8); 1.9696 (0.9); 1.6958 (16.0); 1.6786 (15.8); 1.0356 (2.0); 1.0245 (5.8); 1.0189 (6.1); 1.0084 (3.2); 1.0036 (5.8); 0.9981 (5.8); 0.9878 (2.2); 0.7627 (2.4); 0.7519 (6.9); 493.5 0.7469 (6.6); 0.7397 (6.3); 0.7347 (7.1); 0.7232 (1.9); 0.1458 (0.9); 0.0078 (7.8); ?0.0002 (199.0); ?0.0085 (6.2); ?0.1497 (0.9) I-3 [00051] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.1845 (4.6); 9.1659 (4.7); 9.0615 (7.3); 9.0576 (7.1); 9.0560 (7.3); 8.5657 (4.8); 8.5601 (4.8); 8.5446 (5.2); 8.5390 (5.4); 8.3954 (4.5); 8.3922 (5.8); 8.3834 (4.9); 8.3802 (5.9); 8.3186 (0.4); 8.2394 (4.8); 8.2361 (5.8); 8.2195 (5.3); 8.2161 (6.0); 8.1296 (7.6); 8.1085 (7.1); 7.6224 (8.9); 7.5245 (6.5); 7.4608 (4.8); 7.4484 (8.5); 7.4411 (10.5); 7.4288 (4.7); 5.8730 (0.6); 5.8560 (2.7); 5.8383 (4.3); 5.8207 (2.8); 5.8036 (0.6); 3.3310 (188.4); 3.3075 (0.4); 2.6758 (1.3); 2.6717 (1.9); 2.6676 (1.5); 2.5249 (4.4); 2.5070 (216.7); 2.5027 (298.2); 2.4986 (230.6); 2.4608 (0.4); 2.3339 (1.4); 2.3296 (1.9); 2.3254 (1.5); 2.0761 (6.6); 1.8582 (0.3); 1.8396 (2.8); 1.8306 (7.8); 1.8240 (8.8); 1.8140 (3.8); 1.7976 (0.5); 1.7851 (0.4); 1.7081 (16.0); 1.6910 (16.0); 1.6673 (0.7); 1.6391 (1.0); 1.6333 (0.7); 1.6205 (6.8); 1.6151 (4.6); 1.6093 (7.0); 1.5995 (5.0); 1.5960 (4.8); 1.5853 (0.6); 1.5770 (0.8); 518.4 1.2318 (0.4); 1.2229 (0.4); 1.2171 (0.3); 1.2058 (0.3); 0.1458 (1.2); 0.0179 (0.3); 0.0078 (8.2); ?0.0002 (261.2); ?0.0082 (10.2); ?0.1498 (1.2) I-4 [00052] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.4356 (4.3); 9.4171 (4.5); 9.0896 (6.6); 9.0881 (7.1); 9.0841 (7.2); 9.0824 (6.8); 8.5834 (5.6); 8.5777 (5.4); 8.5623 (6.2); 8.5566 (6.2); 8.4015 (5.4); 8.3979 (5.8); 8.3895 (5.6); 8.3860 (5.8); 8.3182 (1.4); 8.2797 (5.6); 8.2762 (10.0); 8.2727 (5.9); 8.2403 (5.5); 8.2367 (5.7); 8.2203 (6.2); 8.2167 (5.9); 8.1650 (7.3); 8.1635 (7.5); 8.1439 (6.7); 8.1423 (6.8); 8.0588 (6.0); 7.9932 (0.4); 7.9501 (6.0); 7.4634 (5.5); 7.4514 (5.4); 7.4434 (5.2); 7.4314 (5.4); 5.9003 (0.6); 5.8827 (2.8); 5.8651 (4.4); 5.8473 (2.8); 5.8301 (0.6); 3.4040 (0.3); 3.3732 (2.8); 3.3645 (0.9); 3.3368 (62.9); 3.3303 (610.6); 3.2997 (0.6); 3.2843 (0.3); 2.6758 (3.9); 2.6713 (5.5); 2.6668 (4.1); 2.6622 (1.9); 2.6191 (0.4); 2.6140 (0.4); 2.5248 (13.3); 2.5201 (19.4); 2.5112 (303.9); 2.5069 (643.6); 2.5023 (863.6); 2.4978 (616.5); 2.4934 (289.2); 2.4318 (0.5); 2.4106 (0.4); 2.3337 531.0 (3.8); 2.3291 (5.4); 2.3247 (3.8); 2.3202 (1.8); 1.7181 (16.0); 1.7009 (16.0); 1.2477 (1.8); 1.2346 (2.3); 1.2184 (1.6); 0.1460 (4.1); 0.0411 (0.4); 0.0380 (0.4); 0.0339 (0.5); 0.0292 (0.6); 0.0213 (0.8); 0.0165 (1.1); 0.0080 (30.9); ?0.0002 (1009.5); ?0.0085 (32.7); ?0.0279 (0.8); ?0.0316 (0.7); ?0.0365 (0.4); ?0.0432 (0.4); ?0.0681 (0.5); ?0.1495 (4.2) I-5 [00053] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.3635 (4.4); 9.3454 (4.5); 9.0988 (7.0); 9.0933 (7.0); 8.7591 (0.3); 8.7519 (0.3); 8.5978 (5.0); 8.5921 (4.8); 8.5766 (5.4); 8.5710 (5.4); 8.3992 (4.7); 8.3958 (5.4); 8.3872 (5.1); 8.3838 (5.4); 8.3186 (0.7); 8.2984 (0.5); 8.2373 (5.0); 8.2339 (5.3); 8.2174 (5.5); 8.2139 (5.4); 8.1806 (0.4); 8.1673 (7.9); 8.1558 (4.8); 8.1522 (10.1); 8.1479 (11.6); 8.1293 (5.5); 8.1249 (9.2); 8.1207 (5.0); 8.0713 (0.4); 8.0402 (5.7); 8.0360 (8.8); 8.0320 (5.4); 7.9088 (0.5); 7.8858 (0.4); 7.4609 (5.0); 7.4489 (4.8); 7.4408 (4.8); 7.4288 (4.8); 5.8843 (0.6); 5.8674 (2.8); 5.8498 (4.4); 5.8322 (2.8); 5.8150 (0.6); 5.7587 (11.8); 3.3954 (0.4); 3.3667 (0.5); 3.3494 (2.1); 3.3307 (323.5); 3.3073 (46.4); 2.6759 (2.2); 2.6714 (3.1); 2.6670 (2.3); 2.5614 (0.4); 2.5565 (0.5); 2.5248 (7.9); 2.5200 (11.3); 2.5110 (173.1); 2.5069 (368.0); 2.5024 (499.5); 2.4980 (365.3); 481.0 2.4680 (1.0); 2.4636 (0.9); 2.3336 (2.3); 2.3293 (3.2); 2.3249 (2.4); 1.7042 (16.0); 1.6870 (15.9); 1.3510 (0.6); 1.2965 (0.3); 1.2579 (0.7); 1.2436 (2.6); 1.2290 (3.2); 1.2125 (1.4); 1.1929 (0.6); 1.1882 (0.6); 1.1199 (0.3); 0.8525 (0.4); 0.1459 (2.7); 0.0272 (0.4); 0.0079 (17.6); ?0.0002 (581.2); ?0.0082 (22.2); ?0.0207 (0.9); ?0.0257 (0.6); ?0.0293 (0.4); ?0.0352 (0.4); ?0.0382 (0.5); ?0.1496 (2.7) I-6 [00054] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.2286 (3.9); 9.2103 (4.0); 9.0862 (6.7); 9.0821 (6.2); 9.0805 (6.6); 8.5882 (5.0); 8.5825 (4.9); 8.5671 (5.5); 8.5614 (5.5); 8.3991 (4.9); 8.3955 (5.5); 8.3872 (5.4); 8.3835 (5.5); 8.2377 (5.0); 8.2341 (5.2); 8.2177 (5.6); 8.2141 (5.4); 8.1628 (6.8); 8.1615 (7.2); 8.1417 (6.2); 8.1403 (6.8); 8.0493 (5.1); 8.0458 (9.7); 8.0422 (5.8); 7.9280 (4.7); 7.9236 (8.9); 7.9194 (5.8); 7.8910 (6.0); 7.8869 (8.3); 7.8829 (4.8); 7.4614 (5.2); 7.4493 (5.0); 7.4413 (5.0); 7.4293 (5.1); 5.8777 (0.6); 5.8607 (2.7); 5.8431 (4.2); 5.8254 (2.8); 5.8078 (0.6); 3.3316 (84.3); 2.6771 (0.6); 2.6725 (0.8); 2.6680 (0.6); 2.5260 (1.8); 2.5212 (3.0); 2.5125 (44.3); 2.5081 (93.3); 2.5036 (125.3); 2.4990 (88.6); 2.4945 (40.9); 2.4736 (0.5); 2.4688 (0.3); 2.3349 (0.6); 2.3304 (0.8); 2.3259 (0.6); 2.0769 (0.9); 1.8620 (0.4); 1.8466 (2.0); 1.8342 (6.7); 1.8272 (8.3); 1.8236 (6.3); 459.2 1.8158 (2.6); 1.8002 (0.7); 1.7886 (0.4); 1.7043 (15.5); 1.6871 (16.0); 1.6624 (6.5); 1.6588 (4.4); 1.6526 (4.2); 1.6499 (4.2); 1.6389 (5.4); 1.6259 (0.8); 1.6176 (0.8); 1.2441 (1.3); 0.0080 (1.2); ?0.0002 (37.4); ?0.0085 (1.1) I-7 [00055] .sup.1H-NMR(400.2 MHz, CDCl.sub.3) ? = 8.9623 (2.3); 8.9574 (2.4); 8.5790 (2.2); 8.5577 (2.6); 8.4432 (1.6); 8.4399 (1.8); 8.4312 (1.8); 8.4279 (1.9); 8.2885 (1.9); 8.2828 (1.9); 8.2672 (1.6); 8.2615 (1.7); 8.2005 (1.7); 8.1963 (3.1); 8.1920 (2.0); 8.1259 (1.6); 8.1226 (1.8); 8.1060 (1.8); 8.1025 (1.8); 8.0757 (2.2); 8.0723 (3.6); 8.0688 (2.0); 7.9174 (2.8); 7.7894 (1.0); 7.7707 (1.0); 7.4083 (1.8); 7.3962 (1.7); 7.3883 (1.7); 7.3762 (1.6); 7.2654 (18.6); 6.2133 (1.0); 6.1951 (1.5); 6.1778 (1.0); 2.0111 (3.4); 1.7828 (15.6); 1.7754 (16.0); 1.7649 (8.0); 1.7480 (7.4); 1.6837 (9.8); 0.0080 (0.8); ?0.0002 (27.2) 461.3 I-8 [00056] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.4137 (4.0); 9.3953 (4.1); 8.6180 (7.2); 8.6116 (7.3); 8.3615 (4.7); 8.3580 (5.4); 8.3496 (5.0); 8.3461 (5.2); 8.3174 (1.3); 8.3006 (6.4); 8.2804 (15.1); 8.2178 (4.9); 8.2143 (5.1); 8.1978 (5.4); 8.1943 (5.2); 8.1464 (4.7); 8.1398 (4.5); 8.1250 (5.4); 8.1183 (5.3); 7.8430 (8.1); 7.8216 (7.1); 7.4260 (5.0); 7.4140 (4.9); 7.4059 (4.7); 7.3940 (4.7); 5.8044 (0.6); 5.7874 (2.7); 5.7699 (4.2); 5.7522 (2.8); 5.7348 (0.6); 3.9018 (2.3); 3.4680 (0.4); 3.4354 (0.4); 3.4140 (0.5); 3.4016 (0.8); 3.3938 (0.7); 3.3867 (0.9); 3.3564 (2.2); 3.3310 (1284.4); 3.3095 (3.9); 3.2887 (0.4); 3.2822 (0.8); 2.6755 (4.2); 2.6712 (5.6); 2.6668 (4.2); 2.6459 (0.4); 2.6070 (0.4); 2.5705 (0.9); 2.5661 (0.9); 2.5605 (1.0); 2.5246 (12.7); 2.5198 (19.4); 2.5109 (297.7); 2.5067 (628.4); 2.5023 (850.2); 2.4978 (615.3); 2.4597 (0.7); 2.3335 (3.7); 2.3291 (5.3); 2.3246 (3.8); 1.7093 514.3 (16.0); 1.6920 (16.0); 1.2342 (0.3); 0.1459 (1.5); 0.0079 (10.4); ?0.0002 (333.6); ?0.0084 (11.2); ?0.0223 (0.7); ?0.1498 (1.4) I-9 [00057] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.2496 (4.1); 9.2311 (4.2); 8.6140 (6.9); 8.6080 (7.1); 8.3609 (4.7); 8.3574 (5.4); 8.3489 (5.1); 8.3454 (5.3); 8.3184 (0.4); 8.2146 (4.8); 8.2111 (5.0); 8.1947 (5.4); 8.1911 (5.1); 8.1497 (4.7); 8.1431 (4.5); 8.1283 (5.3); 8.1216 (5.3); 7.8615 (1.5); 7.8447 (8.2); 7.8231 (7.1); 7.7253 (5.0); 7.7047 (13.3); 7.4248 (5.0); 7.4128 (4.8); 7.4048 (4.8); 7.3928 (4.8); 5.7744 (0.6); 5.7572 (2.8); 5.7395 (4.2); 5.7217 (2.8); 5.7046 (0.6); 3.3297 (133.5); 2.6764 (1.2); 2.6720 (1.6); 2.6675 (1.2); 2.5254 (4.0); 2.5206 (5.9); 2.5118 (86.6); 2.5075 (183.5); 2.5030 (247.6); 2.4985 (178.0); 2.4942 (84.1); 2.3387 (0.6); 2.3343 (1.2); 2.3298 (1.6); 2.3253 (1.2); 1.6885 (16.0); 1.6713 (15.9); 0.0080 (1.2); ?0.0002 (37.7); ?0.0084 (1.2) 546.1 I-10 [00058] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.3289 (4.4); 9.3104 (4.4); 8.6669 (0.3); 8.6556 (7.3); 8.6492 (7.4); 8.3615 (4.8); 8.3580 (5.6); 8.3496 (5.2); 8.3461 (5.6); 8.2216 (0.3); 8.2119 (5.1); 8.2085 (5.4); 8.1924 (9.8); 8.1880 (7.0); 8.1868 (7.0); 8.1714 (5.8); 8.1647 (6.4); 8.1616 (5.7); 8.1577 (10.1); 8.1541 (6.8); 8.1264 (5.4); 8.1219 (9.0); 8.1177 (5.2); 8.0256 (5.6); 8.0213 (8.7); 8.0172 (5.5); 7.8679 (8.3); 7.8464 (7.3); 7.4232 (5.3); 7.4112 (5.1); 7.4032 (4.9); 7.3912 (4.9); 5.7750 (0.6); 5.7577 (2.8); 5.7399 (4.3); 5.7222 (2.8); 5.7049 (0.6); 3.3305 (107.4); 3.3056 (46.1); 2.6767 (0.6); 2.6720 (0.8); 2.6676 (0.6); 2.5254 (2.1); 2.5119 (43.8); 2.5076 (92.1); 2.5031 (124.3); 2.4987 (91.1); 2.4945 (44.5); 2.3346 (0.6); 2.3300 (0.8); 2.3256 (0.6); 2.0764 (1.9); 1.6855 (16.0); 1.6683 (15.9); 1.6264 (0.6); 1.6092 (0.6); 1.2295 (0.4); 0.0078 (0.7); ?0.0002 (18.8); 490.1 ?0.0084 (0.6) I-11 [00059] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.1514 (4.3); 9.1326 (4.4); 8.6197 (7.4); 8.6132 (7.7); 8.3586 (4.7); 8.3551 (5.4); 8.3467 (5.2); 8.3432 (5.4); 8.3182 (0.4); 8.2132 (5.0); 8.2097 (5.2); 8.1932 (5.6); 8.1897 (5.4); 8.1559 (4.9); 8.1493 (4.7); 8.1345 (5.6); 8.1279 (5.5); 7.8403 (8.5); 7.8189 (7.5); 7.6211 (4.8); 7.6177 (8.7); 7.6142 (5.9); 7.5328 (5.9); 7.4417 (6.2); 7.4233 (5.2); 7.4113 (5.0); 7.4033 (4.9); 7.3913 (4.9); 5.7708 (0.6); 5.7535 (2.7); 5.7357 (4.2); 5.7179 (2.8); 5.7005 (0.6); 3.3298 (152.4); 2.6763 (1.0); 2.6718 (1.4); 2.6674 (1.0); 2.5252 (3.5); 2.5204 (5.0); 2.5116 (74.1); 2.5073 (158.1); 2.5028 (214.5); 2.4984 (155.0); 2.4941 (74.2); 2.3340 (1.0); 2.3297 (1.4); 2.3251 (1.0); 2.0761 (2.3); 1.8605 (0.4); 1.8441 (3.6); 1.8335 (6.9); 1.8270 (8.7); 1.8227 (4.7); 1.8175 (4.4); 1.8012 (0.4); 1.7874 (0.4); 1.6889 (16.0); 1.6717 (16.0); 1.6419 (0.5); 1.6359 (0.9); 1.6304 (0.6); 1.6182 (6.3); 1.6118 (4.4); 1.6067 527.4 (7.0); 1.5974 (4.3); 1.5929 (4.2); 1.5833 (0.6); 1.5755 (0.7); 1.2484 (0.4); 0.0078 (0.5); ?0.0002 (17.1); ?0.0083 (0.6) I-12 [00060] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.4034 (4.3); 9.3848 (4.4); 8.6428 (7.3); 8.6368 (7.4); 8.3641 (4.9); 8.3606 (5.6); 8.3522 (5.4); 8.3486 (5.6); 8.3176 (0.5); 8.2876 (5.3); 8.2842 (9.8); 8.2808 (6.0); 8.2148 (5.1); 8.2113 (5.3); 8.1948 (5.6); 8.1913 (5.5); 8.1760 (5.0); 8.1694 (4.8); 8.1546 (5.7); 8.1480 (5.6); 8.0565 (5.9); 7.9464 (6.0); 7.8676 (8.3); 7.8460 (7.2); 7.4261 (5.2); 7.4141 (5.0); 7.4061 (5.0); 7.3941 (5.0); 5.7901 (0.6); 5.7730 (2.8); 5.7553 (4.2); 5.7375 (2.8); 5.7203 (0.6); 3.3737 (0.4); 3.3346 (58.0); 3.3299 (270.6); 2.6761 (1.3); 2.6716 (1.8); 2.6671 (1.3); 2.5524 (0.3); 2.5250 (4.4); 2.5203 (6.4); 2.5114 (97.1); 2.5071 (208.3); 2.5026 (282.9); 2.4981 (204.0); 2.4938 (97.0); 2.3340 (1.3); 2.3295 (1.8); 2.3249 (1.3); 2.0757 (2.8); 1.6977 (16.0); 1.6805 (16.0); 0.0079 (1.3); ?0.0002 (45.8); ?0.0085 (1.5) 540.1 I-13 [00061] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 8.9973 (4.3); 8.9786 (4.4); 8.6172 (6.9); 8.6110 (7.0); 8.3513 (4.6); 8.3478 (5.3); 8.3393 (5.0); 8.3359 (5.3); 8.3181 (0.5); 8.2033 (4.8); 8.1998 (5.0); 8.1833 (5.3); 8.1799 (5.2); 8.1546 (4.6); 8.1480 (4.5); 8.1332 (5.2); 8.1266 (5.2); 7.8289 (7.9); 7.8075 (7.0); 7.4171 (4.9); 7.4051 (4.7); 7.3971 (4.7); 7.3851 (4.6); 7.3243 (5.8); 7.3032 (8.4); 7.2518 (5.9); 5.7503 (0.6); 5.7329 (2.7); 5.7151 (4.1); 5.6973 (2.7); 5.6801 (0.6); 3.3290 (149.6); 2.6760 (1.2); 2.6716 (1.6); 2.6672 (1.2); 2.5249 (4.0); 2.5201 (6.0); 2.5111 (87.0); 2.5070 (183.4); 2.5026 (247.4); 2.4982 (179.9); 2.3338 (1.2); 2.3294 (1.6); 2.3250 (1.2); 2.0377 (0.7); 2.0250 (1.6); 2.0165 (1.8); 2.0042 (3.3); 1.9917 (2.0); 1.9833 (1.7); 1.9706 (0.9); 1.6746 (16.0); 1.6574 (15.9); 1.0356 (1.9); 1.0245 (5.4); 1.0191 (6.0); 1.0086 (3.0); 1.0037 (5.5); 0.9982 (5.8); 0.9879 (2.2); 0.7660 502.2 (2.3); 0.7553 (6.6); 0.7505 (6.7); 0.7432 (6.1); 0.7381 (7.0); 0.7267 (1.9); 0.0079 (1.1); ?0.0002 (36.0); ?0.0084 (1.2) I-14 [00062] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.1704 (1.0); 9.1517 (1.0); 8.6165 (1.7); 8.6101 (1.7); 8.3590 (1.1); 8.3555 (1.2); 8.3470 (1.2); 8.3435 (1.2); 8.2145 (1.1); 8.2110 (1.1); 8.1945 (1.2); 8.1910 (1.2); 8.1456 (1.1); 8.1390 (1.0); 8.1242 (1.2); 8.1177 (1.2); 7.8391 (2.0); 7.8273 (2.0); 7.8237 (1.3); 7.8178 (1.8); 7.6380 (1.4); 7.5950 (1.3); 7.4242 (1.1); 7.4122 (1.1); 7.4041 (1.1); 7.3922 (1.1); 5.7645 (0.6); 5.7468 (0.9); 5.7288 (0.6); 3.3291 (158.8); 2.6757 (0.7); 2.6711 (1.0); 2.6667 (0.8); 2.5245 (2.6); 2.5197 (3.7); 2.5109 (54.5); 2.5066 (115.7); 2.5021 (156.6); 2.4977 (112.3); 2.4933 (53.0); 2.3334 (0.7); 2.3289 (1.0); 2.3245 (0.8); 1.7374 (0.7); 1.7089 (16.0); 1.6972 (3.9); 1.6800 (3.6); 0.1458 (0.7); 0.0079 (4.9); ?0.0002 (158.6); ?0.0084 (5.3); ?0.1496 (0.7) 529.2 I-15 [00063] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.4531 (4.1); 9.4349 (4.2); 9.0790 (6.9); 9.0734 (6.9); 8.5677 (4.6); 8.5620 (4.6); 8.5466 (5.0); 8.5409 (5.1); 8.4008 (4.6); 8.3974 (5.4); 8.3889 (4.9); 8.3854 (5.4); 8.3188 (0.4); 8.3029 (6.7); 8.2879 (15.7); 8.2428 (4.7); 8.2395 (5.1); 8.2229 (5.2); 8.2194 (5.2); 8.1458 (7.5); 8.1247 (6.8); 7.4641 (4.8); 7.4521 (4.6); 7.4441 (4.6); 7.4321 (4.6); 5.9083 (0.6); 5.8913 (2.8); 5.8736 (4.3); 5.8561 (2.8); 5.8386 (0.6); 3.3362 (150.2); 2.6778 (0.6); 2.6734 (0.9); 2.6689 (0.7); 2.5266 (2.3); 2.5128 (46.4); 2.5087 (97.5); 2.5043 (132.1); 2.4999 (96.9); 2.3355 (0.6); 2.3311 (0.8); 2.3269 (0.6); 2.0775 (0.5); 1.7308 (16.0); 1.7136 (15.9); ?0.0002 (1.0) 505.2 I-16 [00064] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.2805 (4.2); 9.2622 (4.3); 9.0630 (6.9); 9.0575 (6.8); 8.5638 (5.0); 8.5581 (4.8); 8.5426 (5.4); 8.5370 (5.5); 8.3988 (4.7); 8.3953 (5.5); 8.3868 (5.2); 8.3833 (5.5); 8.3185 (0.4); 8.2411 (5.0); 8.2376 (5.3); 8.2211 (5.5); 8.2175 (5.4); 8.1399 (7.4); 8.1188 (6.8); 7.7307 (5.2); 7.7026 (13.1); 7.4628 (5.1); 7.4508 (4.9); 7.4428 (4.9); 7.4308 (4.9); 5.8801 (0.6); 5.8630 (2.8); 5.8454 (4.3); 5.8278 (2.8); 5.8104 (0.6); 3.3330 (246.1); 2.6772 (0.9); 2.6727 (1.2); 2.6683 (0.9); 2.5260 (2.9); 2.5213 (4.3); 2.5124 (63.4); 2.5081 (135.4); 2.5037 (184.2); 2.4992 (133.5); 2.4950 (63.9); 2.3349 (0.8); 2.3304 (1.1); 2.3260 (0.8); 1.7084 (16.0); 1.6912 (15.9); ?0.0002 (1.2) 537.2 I-17 [00065] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.1038 (2.8); 9.0997 (2.8); 8.7771 (0.3); 8.7738 (0.3); 8.7627 (0.3); 8.6297 (1.7); 8.6104 (1.8); 8.5986 (2.2); 8.5930 (2.1); 8.5775 (2.3); 8.5718 (2.2); 8.5323 (0.3); 8.5288 (0.3); 8.3861 (2.1); 8.3826 (2.3); 8.3741 (2.3); 8.3706 (2.2); 8.2227 (2.1); 8.2192 (2.1); 8.2028 (2.4); 8.1992 (2.1); 8.1675 (3.0); 8.1662 (3.0); 8.1463 (2.7); 8.1450 (2.7); 7.5378 (0.4); 7.5269 (0.3); 7.5168 (0.4); 7.5058 (0.3); 7.4516 (2.3); 7.4396 (2.1); 7.4317 (3.2); 7.4196 (2.0); 7.3180 (0.6); 7.2983 (2.9); 7.1650 (1.4); 6.9982 (0.6); 6.8572 (3.9); 5.8263 (1.2); 5.8083 (1.7); 5.7902 (1.2); 3.9791 (2.9); 3.9437 (16.0); 3.3342 (47.6); 2.6767 (0.4); 2.6721 (0.5); 2.6675 (0.4); 2.5252 (1.8); 2.5118 (31.1); 2.5076 (61.4); 2.5031 (79.7); 423.2 2.4986 (56.6); 2.4943 (26.8); 2.3345 (0.4); 2.3299 (0.5); 2.3254 (0.4); 1.6178 (7.0); 1.6007 (7.0); 0.0079 (1.1); ?0.0002 (26.2); ?0.0084 (1.0) I-18 [00066] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.2311 (2.2); 9.2128 (2.2); 9.0676 (3.4); 9.0632 (3.6); 8.5647 (2.1); 8.5594 (2.1); 8.5436 (2.2); 8.5383 (2.3); 8.2444 (3.4); 8.2321 (3.6); 8.1369 (0.5); 8.1064 (3.4); 8.0853 (3.1); 7.7805 (4.3); 7.7558 (3.4); 7.5753 (3.5); 7.2803 (3.0); 7.2680 (2.9); 5.8449 (0.3); 5.8281 (1.3); 5.8108 (2.1); 5.7931 (1.4); 5.7758 (0.4); 3.6338 (0.6); 3.6236 (0.6); 3.6174 (0.8); 3.6073 (0.8); 3.6012 (0.7); 3.5910 (0.6); 3.5749 (0.3); 3.4016 (45.1); 3.1672 (0.3); 3.1491 (0.9); 3.1382 (1.0); 3.1308 (1.0); 3.1200 (0.9); 3.1021 (0.3); 2.6730 (0.7); 2.6344 (16.0); 2.5041 (95.3); 2.3310 (0.6); 2.2069 (0.6); 1.7122 (7.7); 1.6950 (7.7); 1.4995 (0.3); 1.2882 (6.2); 1.2713 (8.0); 1.2670 (8.4); 1.2584 (4.9); 1.2502 (6.8); 1.2401 (2.2); ?0.0002 (8.4) 501.2 I-19 [00067] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.7377 (0.4); 9.2776 (0.5); 9.2251 (2.2); 9.2068 (2.2); 9.0639 (3.6); 9.0584 (3.5); 8.5720 (2.4); 8.5663 (2.3); 8.5509 (2.6); 8.5452 (2.6); 8.5020 (0.4); 8.4963 (0.4); 8.2403 (3.6); 8.2369 (3.8); 8.1496 (3.8); 8.1284 (3.5); 8.0489 (0.8); 8.0420 (0.7); 8.0337 (3.7); 8.0310 (3.8); 7.9710 (0.3); 7.8398 (0.4); 7.8050 (0.8); 7.7945 (2.5); 7.7904 (4.6); 7.7868 (3.4); 7.7575 (3.0); 7.7034 (0.4); 7.6814 (0.3); 7.5846 (3.2); 5.8698 (0.3); 5.8527 (1.4); 5.8352 (2.2); 5.8175 (1.5); 3.3709 (0.4); 3.3362 (117.2); 2.6776 (0.4); 2.6730 (0.5); 2.6689 (0.4); 2.5263 (1.7); 2.5126 (28.5); 2.5086 (57.8); 2.5041 (77.1); 2.4997 (56.5); 2.4526 (16.0); 2.3354 (0.4); 2.3310 (0.5); 2.3266 (0.4); 2.2852 (2.0); 2.1135 (0.8); 2.0769 (0.4); 2.0563 (0.7); 1.6841 (8.2); 1.6669 (8.2); 501.2 1.4413 (0.9); 1.4232 (0.9); ?0.0002 (1.1) I-20 [00068] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.1828 (4.3); 9.1642 (4.4); 9.0572 (6.7); 9.0521 (6.8); 8.5721 (4.7); 8.5665 (4.6); 8.5510 (5.1); 8.5453 (5.1); 8.3178 (0.5); 8.1205 (7.4); 8.0966 (10.2); 8.0758 (8.7); 8.0484 (0.4); 7.7766 (8.8); 7.7731 (6.9); 7.7551 (6.0); 7.5708 (6.3); 7.3062 (7.9); 7.2857 (7.5); 5.8332 (0.7); 5.8160 (2.7); 5.7983 (4.2); 5.7807 (2.8); 5.7583 (3.6); 3.3823 (0.4); 3.3317 (244.0); 2.8915 (1.0); 2.7319 (0.8); 2.6763 (1.1); 2.6721 (1.5); 2.6678 (1.2); 2.5480 (37.9); 2.5255 (4.2); 2.5075 (172.2); 2.5032 (231.4); 2.4989 (172.0); 2.4683 (1.3); 2.3343 (1.1); 2.3300 (1.5); 2.3257 (1.2); 1.6937 (0.5); 1.6703 (16.0); 1.6532 (15.9); 1.2328 (0.6); ?0.0002 (1.2) 501.2 I-21 [00069] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.4423 (2.2); 9.4238 (2.2); 9.0762 (3.4); 9.0712 (3.8); 8.5748 (2.3); 8.5692 (2.4); 8.5537 (2.4); 8.5482 (2.6); 8.3174 (0.7); 8.2814 (5.0); 8.2427 (4.2); 8.1680 (3.9); 8.1468 (3.5); 8.0552 (3.5); 8.0343 (4.1); 7.9541 (3.6); 7.9248 (0.3); 5.9065 (0.4); 5.8887 (1.4); 5.8714 (2.2); 5.8542 (1.5); 5.8367 (0.4); 3.4125 (0.6); 3.3981 (0.7); 3.3828 (1.6); 3.3295 (357.4); 3.2989 (0.8); 3.2677 (0.4); 3.2536 (0.3); 2.6755 (2.0); 2.6712 (2.8); 2.6671 (2.3); 2.5808 (0.5); 2.5064 (318.7); 2.5023 (432.9); 2.4980 (345.4); 2.4533 (16.0); 2.3810 (0.5); 2.3328 (2.0); 2.3291 (2.8); 2.3249 (2.3); 1.7059 (8.0); 1.6887 (8.0); 1.2577 (0.4); 1.2345 (0.8); 1.1358 (0.4); 1.1221 (0.4); ?0.0002 (1.3) 545.3 I-22 [00070] .sup.1H-NMR(400.2 MHz, CD3CN) ? = 9.1139 (3.0); 8.4753 (1.5); 8.4711 (1.7); 8.4543 (1.7); 8.4500 (1.9); 8.3705 (2.1); 8.3587 (2.3); 8.1302 (7.3); 8.1090 (4.7); 8.0883 (2.3); 8.0544 (2.7); 8.0334 (2.4); 7.8368 (1.1); 7.8187 (1.1); 7.3890 (1.5); 7.3773 (1.6); 7.3694 (1.7); 7.3572 (1.5); 5.9895 (1.2); 5.9719 (1.8); 5.9541 (1.2); 3.9174 (16.0); 2.1674 (63.9); 2.1144 (0.6); 2.1085 (0.6); 1.9714 (1.4); 1.9643 (1.3); 1.9519 (18.6); 1.9460 (36.7); 1.9409 (52.1); 1.9350 (41.0); 1.9300 (24.0); 1.7694 (0.4); 1.7644 (0.3); 1.7390 (7.7); 1.7219 (7.8); 1.2682 (1.2); 1.2469 (0.6); 1.2220 (0.5); 1.2040 (0.7); 1.1849 (0.4); 0.8569 (0.3); ?0.0002 (49.3); ?0.0013 (48.9) 538.2 I-23 [00071] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.3962 (4.3); 9.3778 (4.4); 9.0677 (6.9); 9.0623 (7.2); 8.5715 (4.6); 8.5659 (4.6); 8.5504 (5.1); 8.5448 (5.2); 8.3171 (2.0); 8.2656 (9.8); 8.1376 (7.4); 8.1163 (6.9); 8.1000 (8.2); 8.0797 (8.8); 8.0520 (6.5); 7.9398 (6.5); 7.3108 (8.0); 7.2903 (7.7); 5.8674 (0.7); 5.8502 (2.8); 5.8328 (4.4); 5.8151 (2.8); 5.7978 (0.6); 5.7577 (0.3); 3.5066 (0.7); 3.4812 (0.4); 3.4313 (0.6); 3.4097 (1.0); 3.3889 (1.0); 3.3746 (1.6); 3.3301 (1361.4); 3.2962 (1.7); 3.2770 (1.1); 3.2685 (0.6); 3.2406 (0.5); 3.2023 (0.4); 3.1600 (0.4); 3.1406 (0.3); 3.1202 (0.4); 2.7289 (0.4); 2.6754 (5.8); 2.6710 (8.0); 2.6666 (6.2); 2.6031 (0.9); 2.5796 (1.6); 2.5504 (39.1); 2.5243 (20.5); 2.5064 (912.1); 2.5021 (1234.2); 2.4977 (927.7); 2.4543 (1.5); 2.3655 (0.5); 2.3332 (5.8); 2.3289 (7.8); 2.3245 (5.9); 2.2948 (0.4); 545.2 1.6927 (15.9); 1.6756 (16.0); 1.2581 (0.4); 1.2328 (1.4); 1.2032 (0.4); 1.1925 (0.4); 1.1644 (0.4); ?0.0002 (4.0) I-24 [00072] I-24: .sup.1H-NMR(400.2 MHz, CD3CN): ? = 9.1359 (1.8); 9.1316 (1.9); 9.1303 (1.9); 8.5021 (1.4); 8.4963 (1.4); 8.4810 (1.5); 8.4753 (1.5); 8.3731 (1.4); 8.3697 (1.6); 8.3612 (1.5); 8.3577 (1.6); 8.1105 (1.4); 8.1070 (1.5); 8.0902 (1.8); 8.0869 (3.0); 8.0837 (3.1); 8.0802 (2.0); 8.0640 (2.2); 8.0430 (2.0); 7.9215 (0.7); 7.9060 (2.2); 7.8256 (1.8); 7.3905 (1.5); 7.3784 (1.4); 7.3704 (1.4); 7.3584 (1.4); 5.9775 (0.9); 5.9593 (1.4); 5.9415 (1.0); 3.9266 (16.0); 3.6648 (0.4); 3.6483 (0.9); 3.6316 (1.3); 3.6151 (1.0); 3.5986 (0.4); 3.1324 (0.6); 3.1138 (1.7); 3.1032 (15.6); 3.0955 (2.3); 3.0768 (0.6); 2.7281 (5.3); 2.5076 (0.6); 2.2227 (38.6); 2.1219 (0.4); 2.1159 (0.4); 2.1098 (0.4); 2.1035 (0.4); 1.9667 (1.0); 1.9605 (0.7); 1.9548 (9.8); 1.9486 (19.2); 1.9425 (27.7); 1.9363 (19.2); 1.9301 (9.9); 1.7278 (6.6); 1.7105 (6.5); 1.3535 (2.0); 1.3357 (12.5); 1.3196 (10.1); 1.2680 (0.7); 1.1000 (3.2); 1.0848 (3.2); ?0.0002 (11.2); ?0.0083 (0.5) 564.3 I-25 [00073] I-25: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.4344 (3.8); 9.4158 (3.9); 8.9704 (6.0); 8.9647 (6.4); 8.7104 (2.8); 8.6987 (2.8); 8.6880 (1.0); 8.3781 (5.8); 8.3744 (8.0); 8.3658 (4.7); 8.3621 (5.5); 8.3534 (4.1); 8.3187 (0.8); 8.2770 (16.0); 8.2229 (4.1); 8.2196 (4.2); 8.2029 (4.5); 8.1996 (4.3); 7.9364 (6.4); 7.9155 (5.9); 7.4346 (4.0); 7.4226 (3.9); 7.4145 (3.9); 7.4026 (3.9); 5.8779 (0.5); 5.8604 (2.4); 5.8428 (3.7); 5.8252 (2.4); 5.8074 (0.5); 3.9436 (0.5); 3.3780 (0.6); 3.3322 (257.4); 3.2785 (0.3); 2.8117 (15.9); 2.8005 (15.9); 2.6762 (2.6); 2.6717 (3.6); 2.6674 (2.7); 2.6027 (0.4); 2.5908 (0.3); 2.5250 (11.3); 2.5072 (431.8); 2.5028 (571.6); 2.4985 (415.9); 2.3339 537.2 I-26 [00074] I-26: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.4311 (3.7); 9.4122 (3.8); 8.5915 (6.2); 8.5861 (6.3); 8.3795 (4.1); 8.3768 (4.4); 8.3677 (4.3); 8.3650 (4.2); 8.3033 (14.0); 8.2830 (6.1); 8.2378 (4.1); 8.2351 (4.1); 8.2179 (4.3); 8.2150 (4.1); 8.0759 (3.3); 8.0704 (3.3); 8.0553 (4.0); 8.0498 (4.0); 7.8927 (6.3); 7.8722 (5.1); 7.4393 (3.5); 7.4273 (3.5); 7.4193 (3.5); 7.4073 (3.3); 5.9134 (0.6); 5.8967 (2.2); 5.8790 (3.4); 5.8610 (2.2); 5.8441 (0.5); 3.3608 (18.5); 2.9850 (15.2); 2.9404 (0.3); 2.7467 (16.0); 2.6749 (0.6); 2.5728 (0.4); 2.5100 (70.6); 2.5061 (87.9); 2.5023 (66.9); 2.3327 (0.5); 2.0799 (0.5); 1.7179 (12.8); 1.7008 (12.6); 1.2447 (0.4); 1.2336 (0.7); ?0.0002 (0.4) 551.2 I-27 [00075] I-27: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.2769 (2.4); 9.2585 (2.4); 8.9792 (3.8); 8.9741 (3.9); 8.7271 (1.8); 8.7157 (1.8); 8.7053 (0.6); 8.3980 (2.4); 8.3920 (2.4); 8.3761 (4.3); 8.3716 (5.3); 8.3635 (2.9); 8.3600 (3.0); 8.3185 (0.4); 8.2168 (2.6); 8.2134 (2.8); 8.1968 (3.0); 8.1934 (2.9); 7.9403 (3.9); 7.9194 (3.6); 7.6958 (16.0); 7.4321 (2.6); 7.4201 (2.5); 7.4121 (2.5); 7.4001 (2.5); 5.8393 (0.3); 5.8220 (1.5); 5.8044 (2.3); 5.7868 (1.5); 5.7697 (0.3); 3.3311 (121.0); 2.8226 (10.2); 2.8114 (10.2); 2.6763 (1.2); 2.6718 (1.7); 2.6674 (1.2); 2.5252 (4.6); 2.5204 (7.0); 2.5114 (90.0); 2.5073 (189.1); 2.5028 (254.2); 2.4984 (186.3); 2.3342 (1.1); 2.3296 (1.6); 2.3253 (1.2); 1.6939 (8.5); 1.6767 (8.5); ?0.0002 (1.9) 569.2 I-28 [00076] I-28: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.4177 (3.9); 9.3992 (4.1); 8.9819 (6.2); 8.9763 (6.6); 8.7442 (1.1); 8.7340 (3.0); 8.7226 (3.0); 8.7124 (1.1); 8.4015 (3.7); 8.3957 (3.6); 8.3801 (7.5); 8.3757 (7.8); 8.3675 (4.8); 8.3641 (4.6); 8.3184 (0.8); 8.2596 (8.3); 8.2208 (4.4); 8.2175 (4.3); 8.2008 (4.8); 8.1975 (4.4); 8.0322 (5.6); 7.9559 (6.6); 7.9352 (10.9); 7.4348 (4.0); 7.4228 (3.9); 7.4148 (3.8); 7.4028 (3.9); 5.8639 (0.6); 5.8469 (2.4); 5.8291 (3.7); 5.8115 (2.4); 5.7951 (0.6); 3.3792 (0.4); 3.3671 (0.4); 3.3308 (246.2); 2.8228 (16.0); 2.8116 (15.8); 2.6893 (4.0); 2.6758 (2.4); 2.6714 (3.2); 2.6673 (2.4); 2.6156 (0.4); 2.6056 (0.4); 2.5759 (0.5); 2.5247 (9.8); 2.5069 (376.5); 2.5026 (487.2); 2.4983 (350.7); 2.4417 (0.3); 2.3337 (2.3); 2.3294 (3.0); 2.3250 (2.2); 1.7053 (13.3); 1.6881 (13.2); 1.2338 (0.6); ?0.0002 (3.7) 563.2 I-29 [00077] I-29: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.3834 (3.5); 9.3643 (3.6); 8.5939 (5.8); 8.5893 (5.9); 8.3775 (4.0); 8.3740 (4.5); 8.3656 (4.4); 8.3621 (4.5); 8.3186 (0.4); 8.2491 (4.5); 8.2457 (8.1); 8.2424 (5.1); 8.2356 (4.4); 8.2320 (4.4); 8.2155 (4.6); 8.2120 (4.4); 8.1351 (0.4); 8.0737 (3.7); 8.0679 (3.6); 8.0531 (4.6); 8.0474 (4.7); 8.0354 (5.0); 7.9468 (5.0); 7.8863 (6.2); 7.8657 (5.1); 7.4371 (4.1); 7.4251 (4.0); 7.4171 (3.9); 7.4051 (4.0); 6.5916 (0.7); 5.8949 (0.5); 5.8781 (2.2); 5.8601 (3.2); 5.8421 (2.2); 5.8254 (0.5); 3.3735 (0.9); 3.3317 (91.8); 3.0152 (0.5); 2.9846 (15.1); 2.9081 (0.4); 2.7562 (16.0); 2.6765 (1.0); 2.6721 (1.4); 2.6676 (1.0); 2.5254 (4.4); 2.5205 (6.8); 2.5118 (81.6); 2.5075 (168.3); 2.5031 (222.9); 2.4986 (159.9); 2.4944 (76.5); 2.3343 (0.9); 2.3299 (1.3); 2.3254 (0.9); 2.0764 (2.1); 1.7064 (12.6); 1.6893 (12.5); 1.2348 (0.4); ?0.0002 (1.6) 577.3 I-30 [00078] I-30: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.4603 (4.2); 9.4419 (4.4); 9.0219 (6.8); 9.0164 (7.2); 8.4388 (4.0); 8.4330 (4.0); 8.4179 (4.4); 8.4121 (4.4); 8.3795 (4.4); 8.3764 (5.2); 8.3677 (4.8); 8.3644 (5.2); 8.3191 (0.5); 8.2900 (16.0); 8.2708 (6.8); 8.2196 (8.6); 8.2166 (7.5); 8.1994 (5.2); 8.1961 (5.2); 7.9561 (7.1); 7.9352 (6.6); 7.6848 (4.4); 7.4348 (4.3); 7.4228 (4.2); 7.4148 (4.2); 7.4028 (4.2); 5.8784 (0.6); 5.8610 (2.7); 5.8434 (4.2); 5.8257 (2.7); 5.8088 (0.6); 3.3318 (97.8); 2.6771 (1.0); 2.6726 (1.3); 2.6682 (1.0); 2.5257 (3.3); 2.5079 (155.6); 2.5036 (210.7); 2.4994 (159.5); 2.3347 (1.0); 2.3305 (1.3); 2.3262 (1.0); 2.0767 (1.2); 1.7184 (14.9); 1.7012 (15.0); 1.2334 (0.4); 0.8765 (0.6); 0.8597 (0.6); 0.1460 (1.0); 0.0178 (0.4); 0.0078 (7.0); ?0.0002 (216.6); ?0.1496 (1.0) 523.2 I-31 [00079] I-31: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.3193 (3.2); 9.3001 (3.3); 8.9765 (15.6); 8.9642 (16.0); 8.3527 (3.7); 8.3492 (4.2); 8.3408 (4.0); 8.3372 (4.2); 8.2121 (4.0); 8.2085 (4.1); 8.1921 (4.5); 8.1885 (4.2); 7.7272 (4.0); 7.6651 (9.6); 7.6028 (4.1); 7.5905 (7.9); 7.5783 (4.0); 7.4190 (4.1); 7.4070 (3.9); 7.3989 (3.9); 7.3870 (3.9); 5.8105 (0.5); 5.7933 (2.1); 5.7752 (3.0); 5.7571 (2.2); 5.7400 (0.5); 3.3381 (115.2); 2.6778 (0.4); 2.6734 (0.7); 2.6691 (0.5); 2.5267 (1.6); 2.5219 (2.4); 2.5131 (36.3); 2.5089 (76.3); 2.5044 (102.1); 2.4999 (73.3); 2.4956 (34.8); 2.3354 (0.4); 2.3313 (0.6); 2.3268 (0.5); 1.6870 (12.7); 1.6698 (12.7); ?0.0002 (0.4) 513.2 I-32 [00080] I-32: .sup.1H-NMR(600.1 MHz, d.sub.6-DMSO): ? = 20.2266 (0.1); 9.5279 (3.8); 9.5155 (3.9); 9.1007 (6.0); 9.0995 (6.3); 9.0970 (6.4); 9.0957 (6.1); 8.6023 (5.7); 8.5985 (5.6); 8.5884 (5.9); 8.5846 (6.0); 8.5684 (0.2); 8.5262 (5.8); 8.5237 (6.2); 8.5184 (6.5); 8.5158 (6.4); 8.4876 (0.1); 8.4838 (0.1); 8.3446 (0.1); 8.3136 (0.5); 8.2991 (5.2); 8.2827 (12.5); 8.0334 (6.6); 8.0321 (6.6); 8.0195 (6.5); 8.0182 (6.5); 7.9507 (5.7); 7.9482 (6.0); 7.9371 (6.6); 7.9346 (6.4); 7.3723 (6.0); 7.3645 (5.7); 7.3588 (5.8); 7.3509 (6.1); 6.9511 (0.1); 5.7946 (0.6); 5.7833 (2.8); 5.7714 (4.0); 5.7595 (3.0); 5.7536 (2.5); 5.7480 (0.6); 3.7444 (0.1); 3.3160 (145.1); 2.6205 (0.5); 2.6174 (1.2); 2.6143 (1.7); 2.6112 (1.2); 2.6081 (0.6); 2.5384 (0.2); 2.5233 (4.3); 2.5202 (5.3); 2.5171 (4.8); 2.5084 (81.5); 2.5053 (185.4); 2.5022 (263.3); 2.4991 (188.4); 2.4961 (85.8); 2.3922 (0.5); 2.3892 (1.2); 2.3861 (1.7); 2.3830 (1.2); 505.5 2.3800 (0.6); 1.7374 (15.9); 1.7260 (16.0); 1.6470 (0.1); 1.4429 (0.3); 1.4309 (0.3); 1.3857 (0.1); 1.3523 (0.4); 1.3411 (0.1); 1.3369 (0.1); 1.2595 (0.2); 1.2501 (0.3); 1.2345 (0.7); 1.1111 (0.1); 1.0455 (0.5); 1.0433 (0.8); 1.0331 (0.8); 0.8516 (0.3); 0.8190 (0.3); 0.0968 (1.4); 0.0054 (12.0); ?0.0001 (448.0); ?0.0057 (13.9); ?0.0269 (0.1); ?0.1002 (1.4) I-33 [00081] I-33: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.0841 (3.9); 9.0652 (4.0); 8.6535 (6.8); 8.6479 (6.9); 8.6470 (6.7); 8.5014 (5.2); 8.4976 (5.7); 8.4895 (5.7); 8.4857 (5.6); 8.1825 (5.3); 8.1759 (5.2); 8.1612 (6.0); 8.1546 (5.9); 7.8541 (5.0); 7.8503 (5.2); 7.8338 (5.9); 7.8300 (5.6); 7.8198 (7.7); 7.7982 (7.0); 7.3354 (10.5); 7.3234 (10.5); 7.3194 (9.4); 7.3153 (9.0); 7.3032 (5.3); 7.2551 (5.4); 5.6892 (0.6); 5.6720 (2.7); 5.6541 (3.9); 5.6361 (2.8); 5.6189 (0.6); 3.3390 (36.4); 2.6764 (0.4); 2.6719 (0.6); 2.6673 (0.5); 2.5253 (1.9); 2.5206 (2.9); 2.5119 (30.5); 2.5074 (62.6); 2.5028 (83.1); 2.4982 (58.7); 2.4937 (27.2); 2.3342 (0.4); 2.3297 (0.6); 2.3251 (0.4); 2.0746 (7.7); 2.0417 (0.8); 2.0291 (1.7); 2.0206 (1.8); 2.0169 (1.3); 2.0082 (3.5); 1.9996 (1.3); 1.9957 (2.0); 1.9873 (1.8); 1.9747 (0.9); 1.6849 (16.0); 1.6677 (15.9); 502.2 1.0375 (2.2); 1.0268 (5.4); 1.0211 (6.0); 1.0168 (3.1); 1.0108 (3.2); 1.0058 (5.5); 1.0002 (5.9); 0.9900 (2.4); 0.7722 (2.6); 0.7617 (6.6); 0.7565 (6.7); 0.7494 (6.2); 0.7441 (7.0); 0.7329 (2.1); 0.0080 (1.4); ?0.0002 (40.8); ?0.0085 (1.2) I-34 [00082] I-34: .sup.1H-NMR(600.1 MHz, d.sub.6-DMSO): ? = 9.2241 (4.1); 9.2118 (4.1); 9.0812 (6.4); 9.0775 (6.6); 8.5865 (4.3); 8.5828 (4.2); 8.5725 (4.4); 8.5687 (4.4); 8.4308 (4.6); 8.4281 (5.8); 8.3120 (1.0); 8.2529 (3.6); 8.2487 (3.4); 8.2377 (3.7); 8.2338 (3.2); 8.1165 (6.8); 8.1025 (6.4); 7.7834 (8.0); 7.7575 (5.4); 7.5777 (5.7); 5.7990 (2.8); 5.7874 (4.3); 5.7757 (2.8); 3.3260 (186.8); 3.3229 (343.5); 3.3212 (540.8); 3.3168 (566.6); 2.6139 (5.0); 2.5228 (9.8); 2.5198 (12.6); 2.5167 (12.1); 2.5076 (262.0); 2.5048 (580.9); 2.5018 (826.9); 2.4988 (635.9); 2.3857 (5.4); 1.6874 (15.8); 1.6759 (16.0); 0.0053 (2.0); ?0.0001 (80.2) 505.2 I-35 [00083] I-35: .sup.1H-NMR(600.4 MHz, CD3CN): ? = 8.9221 (3.6); 8.9209 (3.7); 8.9184 (3.9); 8.9171 (3.6); 8.3808 (3.3); 8.3784 (3.5); 8.3729 (3.5); 8.3704 (3.5); 8.3275 (3.1); 8.3237 (3.1); 8.3134 (3.9); 8.3096 (4.0); 8.2207 (4.7); 8.2196 (4.7); 8.2066 (3.6); 8.2055 (3.6); 8.1859 (8.6); 8.1321 (3.5); 8.1031 (3.5); 8.1007 (3.6); 8.0898 (3.7); 8.0873 (3.6); 7.8100 (0.9); 7.7998 (1.0); 7.3955 (4.0); 7.3875 (4.0); 7.3822 (3.9); 7.3742 (3.9); 6.0166 (0.6); 6.0050 (2.1); 5.9930 (3.0); 5.9811 (2.2); 5.9695 (0.6); 5.4458 (10.2); 4.0656 (0.9); 4.0537 (0.9); 2.1373 (79.2); 2.1046 (0.9); 2.0541 (0.4); 2.0500 (0.6); 2.0459 (0.4); 1.9715 (4.4); 1.9635 (5.0); 1.9554 (2.2); 1.9512 (2.8); 1.9474 (34.9); 1.9433 (66.7); 1.9392 (98.1); 1.9351 (67.6); 1.9310 (34.2); 1.9223 (0.7); 1.8284 (0.4); 1.8242 (0.6); 1.8201 (0.4); 1.7373 (15.9); 1.7258 (16.0); 1.3792 (0.8); 1.2698 (0.4); 1.2158 (1.2); 1.2039 (2.4); 505.1 1.1921 (1.2); 1.1067 (0.4); 0.0967 (0.6); 0.0054 (4.5); ?0.0001 (161.1); ?0.0057 (5.4); ?0.0127 (0.4); ?0.1001 (0.6) I-36 [00084] I-36: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.5733 (1.4); 9.5552 (1.5); 9.0794 (2.1); 9.0777 (2.4); 9.0739 (2.3); 9.0721 (2.3); 8.5712 (1.8); 8.5655 (1.8); 8.5500 (2.0); 8.5444 (2.0); 8.4068 (1.7); 8.4032 (2.0); 8.3948 (1.9); 8.3912 (2.0); 8.3248 (1.7); 8.3214 (3.2); 8.3180 (2.0); 8.2448 (1.8); 8.2412 (1.9); 8.2248 (2.0); 8.2212 (1.9); 8.1964 (2.0); 8.1943 (1.9); 8.1645 (2.4); 8.1628 (2.6); 8.1434 (2.2); 8.1417 (2.4); 8.1042 (2.0); 7.5603 (1.1); 7.4682 (1.9); 7.4561 (1.8); 7.4481 (1.8); 7.4361 (2.0); 7.4306 (2.6); 7.3008 (1.3); 5.8937 (1.0); 5.8761 (1.5); 5.8584 (1.0); 4.0394 (0.4); 4.0216 (0.4); 3.3419 (86.7); 2.5281 (0.9); 2.5234 (1.4); 2.5146 (15.0); 2.5102 (31.4); 2.5057 (41.9); 2.5011 (30.0); 2.4967 (14.2); 1.9913 (1.8); 1.7261 (5.3); 1.7089 (5.3); 1.3966 (16.0); 1.1943 (0.5); 1.1765 (1.0); 1.1587 (0.5); ?0.0002 (0.7) 566.1 I-37 [00085] I-37: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.2760 (3.2); 9.2577 (3.3); 9.0706 (5.2); 9.0651 (5.2); 8.5675 (3.7); 8.5618 (3.6); 8.5464 (4.0); 8.5407 (4.1); 8.3995 (3.5); 8.3961 (4.2); 8.3876 (3.8); 8.3841 (4.2); 8.2421 (3.7); 8.2386 (4.0); 8.2221 (4.1); 8.2186 (4.2); 8.1426 (5.6); 8.1214 (5.1); 7.8876 (5.7); 7.7347 (4.5); 7.7171 (4.5); 7.4630 (3.8); 7.4510 (3.6); 7.4430 (3.6); 7.4310 (3.6); 5.8937 (0.4); 5.8766 (2.1); 5.8590 (3.2); 5.8414 (2.2); 5.8240 (0.5); 5.7621 (10.3); 3.3434 (55.4); 2.5300 (0.7); 2.5253 (1.0); 2.5163 (15.6); 2.5121 (33.6); 2.5076 (45.7); 2.5032 (33.8); 2.0546 (7.1); 2.0071 (16.0); 1.9930 (0.6); 1.9594 (8.1); 1.7209 (12.0); 1.7037 (12.0); 1.3956 (1.2); 1.2476 (0.4); 1.2320 (0.4); ?0.0002 (0.8) 516.1 I-38 [00086] I-38: .sup.1H-NMR(600.1 MHz, d.sub.6-DMSO): ? = 9.4527 (0.6); 9.4406 (0.6); 9.0998 (1.0); 9.0985 (1.0); 9.0960 (1.0); 9.0947 (1.0); 8.5971 (0.9); 8.5933 (0.9); 8.5831 (1.0); 8.5793 (1.0); 8.4409 (0.7); 8.4383 (0.8); 8.4365 (0.8); 8.4340 (0.7); 8.2885 (0.8); 8.2860 (1.5); 8.2835 (0.8); 8.2606 (0.7); 8.2562 (0.6); 8.2454 (0.8); 8.2410 (0.6); 8.1445 (1.0); 8.1432 (1.0); 8.1305 (1.0); 8.1292 (1.0); 8.0669 (0.7); 8.0657 (0.6); 7.9587 (0.7); 7.9571 (0.6); 5.8441 (0.4); 5.8323 (0.6); 5.8206 (0.4); 3.5231 (0.3); 3.3458 (6.5); 3.3368 (16.0); 3.2228 (0.2); 2.5298 (0.1); 2.5267 (0.1); 2.5236 (0.1); 2.5149 (2.3); 2.5118 (5.1); 2.5087 (7.2); 2.5056 (5.3); 2.5026 (2.4); 1.7199 (2.2); 1.7084 (2.2); 1.6662 (0.1); 1.6547 (0.1); ?0.0001 (1.4) 548.1 I-39 [00087] I-39: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.8386 (0.7); 9.5603 (0.5); 9.5464 (0.5); 9.4507 (4.0); 9.4317 (4.1); 9.3739 (0.4); 9.3714 (0.4); 9.2852 (0.6); 9.2009 (0.5); 9.1981 (0.5); 9.1617 (0.6); 9.0767 (1.4); 8.6246 (7.7); 8.6183 (7.8); 8.6017 (2.1); 8.5446 (0.9); 8.5131 (0.6); 8.4912 (0.4); 8.4705 (0.5); 8.4062 (1.6); 8.3762 (1.5); 8.3187 (1.4); 8.3050 (7.4); 8.2857 (1.3); 8.2471 (16.0); 8.1752 (4.8); 8.1686 (4.6); 8.1539 (5.3); 8.1473 (5.2); 7.8985 (0.3); 7.8797 (0.4); 7.8231 (7.8); 7.8019 (7.0); 7.7714 (0.4); 7.7654 (0.4); 7.7496 (0.5); 7.7423 (0.5); 7.5398 (0.3); 7.4591 (2.9); 7.4462 (2.8); 7.3238 (0.4); 7.2918 (0.7); 7.2685 (0.6); 7.1851 (0.7); 7.0462 (0.4); 5.7551 (0.6); 5.7382 (2.7); 5.7202 (3.8); 5.7023 (2.7); 5.6854 (0.6); 4.5764 (0.3); 4.5591 (0.3); 4.1115 (0.9); 4.0984 (0.9); 3.9729 (1.9); 3.9601 (4.6); 3.7909 (0.4); 3.5683 (0.4); 3.3884 (1.2); 3.3352 (360.3); 3.2693 (0.4); 3.1740 514.3 (5.2); 3.1627 (4.9); 2.6765 (2.8); 2.6720 (3.8); 2.6677 (3.0); 2.5758 (0.4); 2.5568 (0.6); 2.5254 (12.5); 2.5118 (236.1); 2.5076 (466.0); 2.5031 (601.0); 2.4986 (423.1); 2.4944 (198.1); 2.3344 (2.7); 2.3299 (3.7); 2.3256 (2.6); 2.2332 (0.4); 2.2173 (0.4); 1.9094 (0.4); 1.7108 (15.9); 1.6937 (15.8); 1.6289 (1.0); 1.6122 (0.9); 1.5339 (2.0); 1.5160 (2.1); 1.4874 (0.4); 1.4501 (1.4); 1.4324 (1.3); 1.3791 (0.4); 1.3007 (5.6); 1.2590 (1.2); 1.2432 (2.9); 1.2344 (3.6); 1.2272 (2.6); 1.2185 (2.1); 1.2126 (1.6); 1.2067 (1.2); 1.1959 (1.2); 1.1904 (1.1); 1.1747 (0.5); 1.1574 (0.3); 1.0569 (0.4); 1.0476 (0.4); 0.8547 (0.4); 0.0079 (0.5); ?0.0002 (11.3); ?0.0086 (0.4) I-40 [00088] I-40: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.1132 (3.4); 9.0949 (3.6); 9.0846 (5.9); 9.0803 (5.8); 9.0790 (5.6); 8.5862 (4.2); 8.5806 (4.1); 8.5651 (4.6); 8.5595 (4.6); 8.3967 (4.0); 8.3932 (4.6); 8.3848 (4.4); 8.3812 (4.6); 8.2321 (4.2); 8.2286 (4.4); 8.2121 (4.7); 8.2086 (4.5); 8.1574 (5.9); 8.1373 (5.3); 8.1363 (5.4); 7.5967 (0.4); 7.5529 (0.8); 7.4864 (7.3); 7.4578 (4.4); 7.4458 (4.1); 7.4378 (4.1); 7.4316 (0.6); 7.4258 (4.2); 7.3694 (1.6); 7.3601 (12.7); 7.3547 (13.7); 7.3412 (0.4); 7.3031 (15.1); 7.2090 (3.6); 7.2036 (6.3); 7.1983 (3.3); 7.1858 (0.7); 7.1197 (7.7); 7.0934 (0.5); 7.0257 (0.6); 5.8677 (0.5); 5.8506 (2.3); 5.8330 (3.6); 5.8153 (2.3); 5.7980 (0.5); 5.7586 (16.0); 3.3301 (15.4); 2.8644 (1.8); 2.5285 (0.6); 2.5238 (0.9); 2.5150 (14.5); 2.5106 (30.9); 2.5061 (41.7); 2.5015 (30.6); 2.4971 (15.1); 1.7015 (13.0); 1.6843 (13.0); 1.2326 (0.4); 1.2217 (0.4); 1.2169 (0.4); 1.2059 (0.4); 1.1785 (0.4); 1.1184 (0.5) 500.1 I-41 [00089] I-41: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.2083 (1.5); 9.1902 (1.6); 9.0732 (2.6); 9.0678 (2.6); 8.5792 (1.9); 8.5735 (1.9); 8.5582 (2.1); 8.5524 (2.1); 8.3939 (1.9); 8.3904 (2.2); 8.3820 (2.1); 8.3784 (2.2); 8.2346 (2.0); 8.2310 (2.0); 8.2145 (2.2); 8.2109 (2.1); 8.1425 (2.8); 8.1214 (2.6); 7.9105 (1.9); 7.9067 (3.6); 7.9031 (2.4); 7.8610 (2.2); 7.6069 (2.2); 7.4579 (2.1); 7.4458 (2.0); 7.4378 (2.0); 7.4258 (2.0); 5.8418 (1.1); 5.8242 (1.7); 5.8065 (1.1); 3.3224 (406.8); 2.6793 (0.8); 2.6750 (1.7); 2.6704 (2.4); 2.6659 (1.8); 2.6617 (0.8); 2.5408 (1.8); 2.5239 (7.0); 2.5192 (10.0); 2.5105 (133.4); 2.5060 (278.8); 2.5015 (374.2); 2.4969 (271.0); 2.4925 (130.9); 2.3374 (0.8); 2.3328 (1.6); 2.3283 (2.3); 2.3238 (1.7); 2.3193 (0.8); 2.0738 (16.0); 1.6925 (6.4); 1.6753 (6.4); 0.1459 (0.7); 0.0080 (4.8); ?0.0002 (159.4); ?0.0084 (5.3); ?0.1497 (0.7) 530.0 I-42 [00090] I-42: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.2959 (2.8); 9.2776 (2.9); 9.0820 (5.3); 9.0781 (4.9); 9.0764 (5.0); 8.5789 (4.0); 8.5732 (3.8); 8.5578 (4.4); 8.5521 (4.3); 8.3993 (3.8); 8.3956 (4.2); 8.3874 (4.1); 8.3837 (4.1); 8.3149 (0.4); 8.2369 (4.0); 8.2333 (4.0); 8.2168 (6.5); 8.2132 (7.9); 8.2047 (7.2); 8.2011 (8.1); 8.1599 (5.6); 8.1388 (5.1); 7.9208 (4.2); 7.4612 (4.0); 7.4492 (3.8); 7.4411 (3.8); 7.4292 (3.9); 5.8789 (0.5); 5.8615 (2.0); 5.8442 (3.3); 5.8264 (2.2); 5.8095 (0.4); 3.9083 (0.4); 3.4136 (0.4); 3.3858 (0.6); 3.3628 (1.1); 3.3214 (920.5); 3.2659 (0.3); 2.6790 (2.5); 2.6748 (5.1); 2.6702 (7.1); 2.6656 (5.2); 2.6611 (2.4); 2.6288 (0.4); 2.6101 (0.4); 2.6018 (0.5); 2.5942 (0.5); 2.5406 (3.2); 2.5237 (23.0); 2.5189 (35.7); 2.5102 (416.2); 2.5058 (839.8); 2.5012 (1105.7); 2.4967 (789.7); 2.4922 (373.2); 2.4475 (0.6); 2.4209 (0.3); 2.3371 (2.2); 2.3326 (4.9); 2.3281 (6.8); 2.3235 (4.9); 2.3190 (2.3); 2.0737 (16.0); 477.1 1.7019 (12.0); 1.6847 (12.1); 1.2364 (0.4); 0.1458 (2.2); 0.0080 (18.4); ?0.0002 (522.6); ?0.0085 (16.8); ?0.1498 (2.2) I-43 [00091] I-43: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.8445 (1.3); 9.8257 (1.4); 9.0854 (2.3); 9.0799 (2.2); 8.7650 (6.2); 8.7611 (6.4); 8.5800 (1.6); 8.5741 (1.6); 8.5588 (1.8); 8.5532 (1.9); 8.4671 (2.9); 8.4090 (1.6); 8.4054 (1.8); 8.3970 (1.7); 8.3934 (1.8); 8.3156 (0.4); 8.2409 (1.7); 8.2375 (1.8); 8.2210 (1.8); 8.2174 (1.8); 8.1804 (2.4); 8.1585 (2.2); 7.6261 (2.0); 7.4963 (4.6); 7.4685 (1.6); 7.4563 (1.7); 7.4484 (1.6); 7.4364 (1.6); 7.3665 (2.3); 5.9141 (0.9); 5.8966 (1.6); 5.8791 (1.1); 3.6141 (0.4); 3.5141 (0.4); 3.4882 (0.5); 3.4526 (0.5); 3.4475 (0.5); 3.4109 (0.6); 3.3869 (1.0); 3.3650 (1.6); 3.3211 (1387.0); 3.2692 (0.7); 3.2391 (0.4); 3.2209 (0.3); 2.7113 (0.3); 2.6932 (0.6); 2.6747 (7.9); 2.6701 (10.9); 2.6656 (8.2); 2.6610 (4.1); 2.6310 (0.6); 2.5956 (0.7); 2.5910 (0.7); 2.5405 (13.1); 2.5236 (33.6); 2.5189 (48.8); 2.5101 (627.5); 2.5057 (1288.4); 2.5012 (1714.4); 2.4967 (1244.2); 2.4923 (607.5); 2.4181 (0.5); 2.4128 (0.4); 596.1 2.3980 (0.4); 2.3369 (3.4); 2.3327 (7.5); 2.3279 (10.6); 2.3235 (7.8); 2.0857 (0.4); 2.0736 (16.0); 1.7383 (5.2); 1.7212 (5.1); 1.3575 (0.4); 1.3367 (0.4); 1.2368 (0.4); 0.1459 (3.5); 0.0278 (0.5); 0.0079 (24.6); ?0.0002 (786.1); ?0.0085 (27.4); ?0.0219 (1.2); ?0.1497 (3.4) I-44 [00092] I-44: .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.2979 (3.9); 9.2795 (4.0); 9.0678 (6.9); 9.0637 (6.5); 9.0623 (6.8); 8.5633 (4.9); 8.5577 (4.8); 8.5422 (5.5); 8.5366 (5.5); 8.3923 (4.8); 8.3887 (5.5); 8.3803 (5.2); 8.3767 (5.4); 8.2309 (5.0); 8.2274 (5.3); 8.2110 (5.5); 8.2074 (5.4); 8.1465 (7.3); 8.1254 (6.8); 8.0194 (13.4); 7.9041 (6.0); 7.4554 (5.1); 7.4434 (4.9); 7.4353 (5.0); 7.4233 (5.0); 7.2820 (5.7); 7.1434 (13.2); 7.0049 (6.2); 5.8966 (0.6); 5.8797 (2.8); 5.8621 (4.3); 5.8445 (2.8); 5.8261 (0.6); 3.3651 (1.0); 3.3209 (929.8); 3.2645 (0.4); 2.6747 (5.2); 2.6702 (7.5); 2.6656 (5.4); 2.6612 (2.7); 2.6126 (0.5); 2.5406 (12.1); 2.5237 (22.6); 2.5190 (32.8); 2.5101 (420.1); 2.5057 (871.4); 2.5012 (1168.6); 2.4967 (851.3); 2.4922 (414.9); 2.4396 (0.7); 2.4161 (0.4); 2.3371 (2.4); 2.3325 (5.2); 2.3281 (7.3); 2.3236 (5.4); 2.0738 (7.6); 468.1 1.7042 (16.0); 1.6870 (16.0); 1.3562 (0.3); 0.1458 (2.0); 0.0080 (15.1); ?0.0002 (501.7); ?0.0085 (17.0); ?0.0226 (0.5); ?0.1497 (2.1) .sup.1)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. .sup.2)lowT denotes that the measurement was conducted at a temperature of 260 Kelvin. .sup.3)The stated mass corresponds to the peak from the isotope pattern of the [M + H].sup.+ ion with the highest intensity. # denotes that the [M ? H].sup.? ion was recorded.

TABLE-US-00002 TABLE 2 Intermediates ESI Ex- Mass ample Structure.sup.1) NMR Peak List.sup.2) (m/z).sup.3) INT-1 [00093] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO) ? = 9.18-9.17 (dd, 1H), 8.79-8.78 (bd, 2H, NH.sub.2), 8.73-8.71 (dd, 1H), 8.53-8.50 (m, 2H), 8.33-8.31 (dd, 1H), 7.56-7.53 (dd, 1H), 5.27-5.18 (m, 1H), 1.62-1.60 (d, 3H). 265.2 [amine + H.sup.+] INT-2 [00094] 274.1 [amine + H.sup.+] INT-3 [00095] 279.2 [amine + H.sup.+] INT-4 [00096] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 9.1796 (1.2); 9.1750 (1.3); 8.8275 (0.4); 8.8230 (0.4); 8.7908 (1.2); 8.7008 (0.8); 8.6950 (0.8); 8.6794 (0.9); 8.6737 (0.9); 8.5309 (0.9); 8.5276 (1.0); 8.5190 (0.9); 8.5156 (0.9); 8.4508 (1.3); 8.4296 (1.1); 8.3292 (0.9); 8.3260 (0.9); 8.3092 (1.0); 8.3058 (1.0); 8.2873 (0.3); 7.5529 (0.8); 7.5409 (0.8); 7.5328 (0.8); 7.5208 (0.8); 5.2145 (0.4); 3.9582 (7.5); 3.8679 (2.0); 3.8383 (0.6); 3.8208 (0.7); 3.8039 (0.5); 3.7965 (0.5); 3.7717 (0.5); 3.7562 (0.9); 3.7336 (0.4); 3.7155 (0.4); 3.7119 (0.4); 3.7016 (0.4); 3.6804 (0.4); 3.5683 (16.0); 2.5083 (28.6); 2.5040 (37.1); 2.4997 (28.0); 1.6206 (3.0); 1.6038 (3.0); 1.5085 (0.6); 1.4910 (0.6); 1.2336 (0.7); ?0.0002 (3.9) 298.4 [amine + H.sup.+] INT-5 [00097] 279.2 [amine + H.sup.+] INT-6 [00098] 279.2 [amine + H.sup.+] INT-7 [00099] .sup.1H-NMR(400.2 MHz, d.sub.6-DMSO): ? = 11.4123 (1.2); 10.8503 (1.4); 9.7021 (1.8); 9.1542 (2.0); 8.8940 (2.9); 8.8877 (3.0); 8.8240 (2.8); 8.8082 (1.7); 8.7846 (1.1); 8.7691 (1.2); 8.5805 (1.4); 8.5738 (1.4); 8.4838 (1.1); 8.4681 (3.8); 8.4620 (3.4); 8.4465 (1.8); 8.4401 (1.9); 8.1636 (1.8); 8.1475 (1.7); 8.0652 (2.7); 8.0437 (2.6); 8.0400 (1.5); 8.0330 (1.0); 8.0175 (1.2); 8.0109 (1.2); 7.8842 (1.6); 7.8620 (1.2); 4.8996 (0.7); 4.4357 (0.4); 4.4219 (0.5); 4.4066 (0.4); 3.1666 (8.4); 2.5294 (0.9); 2.5118 (28.6); 2.5074 (37.6); 2.5030 (28.4); 2.0791 (16.0); 1.5839 (6.0); 1.5665 (7.4); 1.5461 (3.4) 274.3 [amine + H.sup.+] INT-8 [00100] .sup.1H-NMR (600.1 MHz, d6-DMSO): ? = 8.8227 (1.9); 8.8220 (1.9); 8.8184 (2.0); 8.8176 (1.9); 8.7373 (1.4); 8.7313 (1.4); 8.6617 (0.1); 8.6299 (0.1); 8.6251 (0.1); 8.5961 (1.6); 8.5937 (1.7); 8.5883 (1.8); 8.5858 (1.7); 8.4440 (0.1); 8.3713 (1.7); 8.3669 (1.6); 8.3570 (1.8); 8.3526 (1.7); 8.3167 (0.2); 8.2605 (0.2); 8.2498 (0.2); 8.2288 (0.1); 8.2119 (0.1); 8.1415 (0.2); 8.1378 (0.4); 8.1266 (0.2); 8.1222 (0.1); 8.0741 (1.6); 8.0716 (1.7); 8.0604 (1.8); 8.0579 (1.8); 7.9260 (2.2); 7.9252 (2.1); 7.9117 (2.1); 7.9109 (2.0); 7.7110 (0.1); 7.7065 (0.1); 7.6963 (0.1); 7.6917 (0.1); 7.4599 (1.6); 7.4520 (1.6); 7.4462 (1.6); 7.4383 (1.6); 4.9961 (0.2); 4.9873 (0.4); 274.3 [amine + H.sup.+] 4.9778 (0.5); 4.9671 (0.4); 4.9570 (0.2); 4.7158 (1.1); 4.5296 (0.1); 4.5224 (0.1); 4.5145 (0.1); 4.3305 (0.1); 4.0693 (0.2); 3.7756 (0.2); 3.7713 (0.1); 3.7681 (0.2); 3.7650 (0.1); 3.7606 (0.1); 3.7139 (0.7); 3.6822 (0.1); 3.6743 (0.1); 3.6664 (0.1); 3.5698 (16.0); 3.3937 (0.1); 3.0159 (1.1); 2.8890 (1.0); 2.6922 (4.5); 2.6205 (0.2); 2.6174 (0.3); 2.6144 (0.2); 2.5564 (0.1); 2.5471 (0.2); 2.5378 (0.2); 2.5264 (0.7); 2.5233 (0.8); 2.5202 (0.8); 2.5115 (14.5); 2.5085 (32.2); 2.5054 (45.2); 2.5023 (32.4); 2.4993 (14.8); 2.3924 (0.2); 2.3893 (0.3); 2.3862 (0.2); 1.9102 (0.3); 1.5564 (5.1); 1.5450 (5.1); 1.5359 (0.5); 1.4161 (0.3); 1.4045 (0.3); 1.3942 (0.2); 1.3822 (0.2); 1.3577 (0.3); 1.3088 (0.5); 1.2973 (0.5); 1.2365 (0.4); 1.1125 (0.2); 1.0446 (0.2); 1.0345 (0.2); 0.0968 (0.3); 0.0054 (2.1); ?0.0001 (72.5); ?0.0057 (2.3); ?0.1003 (0.3) .sup.1)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. .sup.2)lowT denotes that the measurement was conducted at a temperature of 260 Kelvin. .sup.3)The stated mass corresponds to the peak from the isotope pattern of the [M + H].sup.+ ion with the highest intensity. # denotes that the [M ? H].sup.? ion was recorded.

Biological Examples

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

[0737] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 ?L 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 ?g/cm.sup.2 is achieved.

[0738] 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 behavior 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.

[0739] A compound shows a good efficacy against Rhipicephalus microplus, if at a compound concentration of 5 ?g/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.

[0740] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 5 ?g/cm.sup.2 (=500 g/ha): I-2.

[0741] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 5 ?g/cm.sup.2 (=500 g/ha): I-3.

[0742] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 5 ?g/cm.sup.2 (=500 g/ha): I-1.

[0743] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 1 ?g/cm.sup.2 (=100 g/ha): 1-2, 1-8, 1-14, 1-15, 1-16, 1-31.

[0744] In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 1 ?g/cm.sup.2 (=100 g/ha): I-1, 1-3, 1-6, 1-7, I-11, I-13.

[0745] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 ?g/cm.sup.2 (=100 g/ha): I-9.

Rhipicephalus (Boophilus) MicroplusInjection Test

[0746] Solvent: Dimethyl Sulfoxide

[0747] 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.

[0748] Five adult engorged female ticks (Rhipicephalus microplus) are injected with 1 ?L compound solution into the abdomen. The ticks are transferred into replica plates and incubated in a climate chamber.

[0749] 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.

[0750] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 4 ?g/tick: I-1, I-2, I-3.

Ctenocephalides felisOral Test [0751] Solvent: Dimethyl Sulfoxide

[0752] 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 citrated cattle blood to the desired concentration.

[0753] Approximately 20 adult unfed cat fleas (Ctenocephalides felis) are placed in a flea chamber whose top and bottom is covered with gauze. A chamber whose bottom is sealed with parafilm, is filled with the blood-compound solution and placed on top of the flea chamber, so that the fleas can suck the blood. The blood chamber is heated to 37? C. whereas the flea chamber is kept at room temperature.

[0754] After 2 days mortality in % is determined. 100% means all the fleas have been killed; 0% means none of the fleas have been killed.

[0755] 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-1.

Ctenocephalides felisIn-Vitro Contact Tests Adult Cat Flea

[0756] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 ?L 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 ?g/cm.sup.2 is achieved.

[0757] 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.

[0758] 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.

[0759] A compound shows a good efficacy against Ctenocephalides felis, if at a compound concentration of 5 ?g/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.

[0760] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 ?g/cm.sup.2 (=100 g/ha): I-15.

Rhipicephalus sanguineusIn-Vitro Contact Tests with Adult Brown Dog Ticks

[0761] 9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 ?L 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 ?g/cm.sup.2 is achieved.

[0762] 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.

[0763] A compound shows a good efficacy against Rhipicephalus sanguineus, if at a compound concentration of 5 ?g/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.

[0764] In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 1 ?g/cm.sup.2 (=100 g/ha): I-17.

[0765] In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 ?g/cm.sup.2 (=100 g/ha): I-8, I-13, I-15.

Aphis gossypiiOral Test [0766] Solvent: 100 Parts by Weight Acetone

[0767] 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.

[0768] 50 ?L compound solution is filled in microtiter plates and 150 ?L IPL41 insect medium (33%+15% sugar) is added to obtain a total volume of 200 ?L per well. Afterwards the plates are sealed with parafilm through which a mixed population of the cotton aphid (Aphis gossypii) can suck on the compound preparation.

[0769] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[0770] 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-4, I-5, I-7, I-9, I-10, I-24, I-27.

Diabrotica BalteataSpray Test

[0771] Solvent: 78.0 Parts by Weight of Acetone [0772] 1.5 parts by weight of dimethylformamide [0773] Emulsifier: Alkylarylpolyglycol Ether

[0774] 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.

[0775] 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).

[0776] 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.

[0777] 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 ?g/well): I-1, I-3, I-4, I-8, I-9, I-11, I-12, I-15, I-16, I-31, I-34, I-35, I-36, I-37, I-38, I-39, I-40, I-41.

Meloidogyne IncognitaTest

[0778] Solvent: 125.0 parts by weight of acetone

[0779] 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.

[0780] 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 lettuce seeds. The lettuce seeds germinate and the seedlings grow. Galls develop in the roots.

[0781] After 14 days the nematicidal effect in percent is determined by the formation of galls. 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.

[0782] 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-25, I-27, I-38.

Myzus persicaeOral Test [0783] Solvent: 100 parts by weight acetone

[0784] 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.

[0785] 50 ?L compound solution is filled in microtiter plates and 150 ?L IPL41 insect medium (33%+15% sugar) is added to obtain a total volume of 200 ?L 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.

[0786] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[0787] 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-4, I-5, I-7, I-9, 1-10, 1-24, I-27.

Myzus persicaeSpray Test [0788] Solvent: 78.0 parts by weight acetone [0789] 1.5 parts by weight dimethylformamide [0790] Emulsifier: alkylarylpolyglycol ether

[0791] 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.

[0792] 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.

[0793] After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.

[0794] 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-9.

[0795] 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-3, I-35.

[0796] 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-6, I-15, I-26, I-31.

Nezara viridulaSpray Test [0797] Solvent: 78.0 parts by weight of acetone [0798] 1.5 parts by weight of dimethylformamide [0799] Emulsifier: alkylarylpolyglycol ether

[0800] 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.

[0801] Barley plants (Hordeum vulgare) are sprayed with a test solution containing the desired concentration of the active ingredient and are infested with larvae of the southern green stink bug (Nezara viridula).

[0802] 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.

[0803] 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-3, I-4, I-5, I-10, I-12, I-25, I-28, I-30, I-31, I-38, I-39.

[0804] 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-29.

Nilaparvata lugensSpray Test [0805] Solvent: 78.0 parts by weight of acetone [0806] 1.5 parts by weight of dimethylformamide [0807] Emulsifier: alkylarylpolyglycol ether

[0808] 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.

[0809] 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).

[0810] After 4 days mortality in % is determined. 100% means all planthoppers have been killed and 0% means none of the planthoppers have been killed.

[0811] 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-1, I-26.

[0812] 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: 1-3, 1-4, 1-15, 1-40.

Spodoptera frugiperdaSpray Test [0813] Solvent: 78.0 parts by weight acetone [0814] 1.5 parts by weight dimethylformamide [0815] Emulsifier: alkylarylpolyglycol ether

[0816] 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.

[0817] 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).

[0818] After 7 days mortality in % is determined. 100% means all caterpillars have been killed and 0% means none of the caterpillars have been killed.

[0819] 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-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-15, I-16, I-20, I-23, I-31, I-32, I-33, I-34, I-35, I-36, I-37, I-38, I-40, I-41, I-42.

[0820] 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-14, I-44.

Aedes aegypti Test (AEDSAE Surface Treatment & Contact Assay) [0821] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0822] 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.

[0823] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-1, I-2, I-3, I-7, I-8, I-10, I-11, I-14, I-15, I-16, I-24, I-26, I-31, I-35, I-40.

[0824] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-3, I-4, I-6, I-10, I-15, I-16, I-24, I-27, I-31, I-35, I-40.

Culex quinquefasciatus Test (CULXFA Surface Treatment & Contact Assay) [0825] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0826] 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 2,000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult mosquitoes of the species Culex quinquefasciatus strain P00 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.

[0827] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-3, I-15, I-24, I-31, I-35.

[0828] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-3, I-10, I-24, I-33.

Musca domestica Test (MUSCDO Surface Treatment & Contact Assay) [0829] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0830] 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.

[0831] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-1, I-2, I-3, I-8, I-9, I-11, I-14, I-15, I-16, I-31, I-35, I-40.

[0832] The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m.sup.2: I-3, I-11, I-15, I-16, I-31, I-35, I-40.

Blattella germanica Test (BLTTGE Surface Treatment & Contact Assay) [0833] Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)

[0834] 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.

[0835] 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.

[0836] The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m.sup.2: I-31.