INHIBITORS OF ALPHA-HEMOLYSIN OF STAPHYLOCOCCUS AUREUS

Abstract

The present invention relates to novel inhibitors of -hemolysin of formula (I) and the use thereof for the prophylaxis and treatment of infections caused by Staphylococcus aureus; especially S. aureus lung infections.

##STR00001##

Claims

1. A compound of formula (I): ##STR00472## wherein R.sup.1 is hydrogen, fluorine or a methyl group; R.sup.2 is halogen, OH, NO.sub.2, CN or NH.sub.2; or a C.sub.1-4 alkyl group, a C.sub.2-4 alkenyl group, a C.sub.2-4 alkynyl group, a C.sub.3-5 cycloalkyl group, an OC.sub.3-5 cycloalkyl group, a C.sub.4-8 alkylcycloalkyl group, or a C.sub.1-4 heteroalkyl group; R.sup.4 is an optionally substituted phenyl group; an optionally substituted naphthyl group; an optionally substituted heteroaryl group containing 1 or 2 rings and 5 to 10 ring atoms selected from O, S, N and C; an optionally substituted cycloalkyl aryl group comprising a phenyl group and a cycloalkyl group containing 5 or 6 ring atoms; an optionally substituted heterocycloalkyl aryl group comprising a phenyl group and a heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, B, N and C; an optionally substituted cycloalkyl heteroaryl group comprising a heteroaryl group comprising 5 or 6 ring atoms selected from O, S, N and C and a cycloalkyl group containing or 6 ring atoms; or an optionally substituted heterocycloalkyl heteroaryl group comprising a heteroaryl group comprising 5 or 6 ring atoms selected from O, S, N and C and a heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, N and C; or an optionally substituted cycloalkyl group containing 1 or 2 rings and 3 to 10 ring atoms; and R.sup.4a is hydrogen; or R.sup.2 and R.sup.4a together are a group of formula O(CH.sub.2).sub.n, wherein n is 1, 2 or 3, wherein the oxygen is bound to the phenyl ring; or a solvate, a hydrate or a salt thereof; wherein the following compounds are excluded: 1. compounds of formula (I) wherein R.sup.1 is H, R.sup.2 is Me, R.sup.4a is hydrogen and R.sup.4 is selected from the following groups: ##STR00473## 2. the compound of the following formula: ##STR00474## wherein R is a group having the following structure: ##STR00475##

2. A compound according to claim 1, wherein R.sup.2 is halogen, OH, NO.sub.2, CN or NH.sub.2; or a C.sub.1-4 alkyl group, a C.sub.2-4 alkenyl group, a C.sub.2-4 alkynyl group, a C.sub.3-5 cycloalkyl group, a C.sub.4-8 alkylcycloalkyl group or a C.sub.1-4 heteroalkyl group; R.sup.4 is an optionally substituted phenyl group; an optionally substituted naphthyl group; an optionally substituted heteroaryl group containing 1 or 2 rings and 5 to 10 ring atoms selected from O, S, N and C; an optionally substituted cycloalkyl aryl group comprising a phenyl group and a cycloalkyl group containing 5 or 6 ring atoms; an optionally substituted heterocycloalkyl aryl group comprising a phenyl group and a heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, N and C; an optionally substituted cycloalkyl heteroaryl group comprising a heteroaryl group comprising 5 or 6 ring atoms selected from O, S, N and C and a cycloalkyl group containing 5 or 6 ring atoms; or an optionally substituted heterocycloalkyl heteroaryl group comprising a heteroaryl group comprising 5 or 6 ring atoms selected from O, S, N and C and a heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, N and C; or an optionally substituted cycloalkyl group containing 1 or 2 rings and 3 to 10 ring atoms; and R.sup.4a is hydrogen; or R.sup.2 and R.sup.4a together are a group of formula O(CH.sub.2).sub.n, wherein n is 1, 2 or 3, wherein the oxygen is bound to the phenyl ring.

3. A compound according to claim 1, wherein R.sup.1 is hydrogen or fluorine; especially hydrogen.

4. A compound according to claim 1, wherein R.sup.2 is F, Cl, Br, a methyl group, an ethyl group, an iso-propyl group, a NO.sub.2 group, a CF.sub.3 group, a methoxy group, a OCF.sub.3 group, a cyclopropyl group, a CN group, a CD.sub.3 group, a CHF.sub.2 group, a CH.sub.2F group, a CH.sub.2OH group, a NHMe group, an O-cyclopropyl group, an OCH.sub.2CF.sub.3 group, an ethoxy group, an NHCH.sub.2CH.sub.2OH group, or a NMe.sub.2 group.

5. A compound according to claim 1, wherein R.sup.2 is F, Cl, Br, a methyl group, an ethyl group, an iso-propyl group, a NO.sub.2 group, a CF.sub.3 group, a methoxy group, a OCF.sub.3 group, a cyclopropyl group, a CN group, a CD.sub.3 group, a CHF.sub.2 group, a CH.sub.2F group, a CH.sub.2OH group or a NMe.sub.2 group; more preferably F, Cl, Br, a methyl group, an ethyl group, iso-propyl group, a methoxy group, a OCF.sub.3 group, a NO.sub.2 group, a cyclopropyl group or a dimethylamino group; most preferably, a methyl group.

6. A compound according to claim 1, wherein R.sup.4 is an optionally substituted phenyl group; an optionally substituted naphthyl group; an optionally substituted heteroaryl group containing 1 or 2 rings and 5 to 10 ring atoms selected from O, S, N and C or an optionally substituted cycloalkyl aryl group comprising a phenyl group and a cycloalkyl group containing 5 or 6 ring atoms or an optionally substituted heterocycloalkyl aryl group comprising a phenyl group and a heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, N and C.

7. A compound according to claim 1, wherein R.sup.4 is an optionally substituted phenyl group; or an optionally substituted heteroaryl group containing 5 or 6 ring atoms selected from O, S, N and C.

8. A compound according to claim 1, wherein R.sup.4 has the following formula: ##STR00476## wherein M.sup.1 is N or CR.sup.7; M.sup.2 is N or CR.sup.5; M.sup.3 is N or CR.sup.5a, and M.sup.4 is N or CR.sup.7a, R.sup.5, R.sup.5a, R.sup.7 and R.sup.7a are independently selected from hydrogen, halogen, CN, a C.sub.1-4 alkyl group, a C.sub.2-4 alkenyl group, a C.sub.2-4 alkynyl group, or a C.sub.1-4 heteroalkyl group; and R.sup.6 is halogen, CN, an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a cycloalkyl group, a heterocycloalkyl group, an alkylcycloalkyl group, a heteroalkylcycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group or a heteroaralkyl group; all of which groups may optionally be substituted; or R.sup.6 is a group of formula OR.sup.6a or NHR.sup.6, wherein R.sup.6a is a cycloalkyl group, a heterocycloalkyl group, an alkylcycloalkyl group, a heteroalkylcycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group or a heteroaralkyl group; all of which groups may optionally be substituted; or R.sup.5 and R.sup.6 together are part of an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms selected from O, S, N and C, an optionally substituted cycloalkyl group containing 5 or 6 ring atoms or an optionally substituted heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, B, N and C.

9. A compound according to claim 8, wherein R.sup.7 is hydrogen or methyl; preferably hydrogen.

10. A compound according to claim 8, wherein R.sup.7a is hydrogen.

11. A compound according to claim 1, wherein R.sup.4 has the following formula: ##STR00477## wherein R.sup.5 and R.sup.5a are independently selected from hydrogen, halogen, CN, a C.sub.1-4 alkyl group, a C.sub.2-4 alkenyl group, a C.sub.2-4 alkynyl group, or a C.sub.1-4 heteroalkyl group; and R.sup.6 is halogen, CN, an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a cycloalkyl group, a heterocycloalkyl group, an alkylcycloalkyl group, a heteroalkylcycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group or a heteroaralkyl group; all of which groups may optionally be substituted; or R.sup.6 is a group of formula OR.sup.6a or NHR.sup.6, wherein R.sup.6a is a cycloalkyl group, a heterocycloalkyl group, an alkylcycloalkyl group, a heteroalkylcycloalkyl group, an aryl group, a heteroaryl group, an aralkyl group or a heteroaralkyl group; all of which groups may optionally be substituted; or R.sup.5 and R.sup.6 together are part of an optionally substituted phenyl group, an optionally substituted heteroaryl group containing 5 or 6 ring atoms selected from O, S, N and C, an optionally substituted cycloalkyl group containing 5 or 6 ring atoms or an optionally substituted heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, B, N and C.

12. A compound according to claim 1, wherein R.sup.5 is hydrogen or methyl; especially hydrogen.

13. A compound according to claim 1, wherein R.sup.5a is hydrogen, Cl, Br, CN, methyl, methoxy, CF.sub.3, OCF.sub.3, NMe.sub.2, CCH, or SO.sub.2Me; especially hydrogen, Cl, Br, methyl or methoxy.

14. A compound according claim 1, wherein R.sup.6 is F, Cl, Br, CN, a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, a C.sub.1-6 heteroalkyl group, an optionally substituted C.sub.3-8 cycloalkyl group, an optionally substituted heterocycloalkyl group containing one or two rings and from 3 to 10 ring atoms selected from O, S, C and N, an optionally substituted phenyl group, an optionally substituted CH.sub.2-phenyl group, an optionally substituted heteroaryl group containing 5 or 6 to 10 ring atoms selected from O, S, N and C or an optionally substituted heterocycloalkyl aryl group comprising a phenyl group and a heterocycloalkyl group containing 4, 5 or 6 ring atoms selected from O, S, N and C; preferably, R.sup.6 is an optionally substituted phenyl group or an optionally substituted heteroaryl group containing 5 or 6 ring atoms selected from O, S, N and C.

15. A compound according to claim 1, wherein R.sup.6 is CN, a C.sub.2-6 alkenyl group, a C.sub.2-6 alkynyl group, a C.sub.2-6 heteroalkyl group, an optionally substituted C.sub.3-8 cycloalkyl group, an optionally substituted heterocycloalkyl group containing one or two rings and from 3 to 10 ring atoms selected from O, S, C and N, an optionally substituted phenyl group, an optionally substituted CH.sub.2-phenyl group, an optionally substituted heteroaryl group containing 5 or 6 to 10 ring atoms selected from O, S, N and C or an optionally substituted heterocycloalkyl aryl group comprising a phenyl group and a heterocycloalkyl group containing 4, 5 or 6 ring atoms selected from O, S, N and C; preferably, R.sup.6 is an optionally substituted phenyl group or an optionally substituted heteroaryl group containing 5 or 6 ring atoms selected from O, S, N and C.

16. A compound according to claim 8, wherein R.sup.6 is an optionally substituted C.sub.3-8 cycloalkyl group, an optionally substituted heterocycloalkyl group containing one or two rings and from 3 to 10 ring atoms selected from O, S, C and N, an optionally substituted phenyl group, an optionally substituted CH.sub.2-phenyl group, an optionally substituted heteroaryl group containing 5 or 6 to 10 ring atoms selected from O, S, N and C or an optionally substituted heterocycloalkyl aryl group comprising a phenyl group and a heterocycloalkyl group containing 4, 5 or 6 ring atoms selected from O, S, N and C; preferably, R.sup.6 is an optionally substituted phenyl group or an optionally substituted heteroaryl group containing 5 or 6 ring atoms selected from O, S, N and C.

17. A compound according to claim 8, wherein R.sup.6 is unsubstituted or substituted by 1, 2 or 3 substituents that are independently selected from halogen, CN, OH, NH.sub.2, O, P(O)Me.sub.2, CONH.sub.2, COOH, a C.sub.1-4 alkyl group, a C.sub.2-4 alkenyl group, a C.sub.2-4 alkynyl group, a C.sub.1-4 heteroalkyl group, a C.sub.3-7 cycloalkyl group, an OC.sub.3-7 cycloalkyl group or a heterocycloalkyl group containing from 3 to 7 ring atoms selected from O, S, C and N; especially wherein R.sup.6 is unsubstituted or substituted by 1, 2 or 3 substituents that are independently selected from halogen, CN, COOH, a C.sub.1-4 alkyl group, a C.sub.2-4 alkenyl group, a C.sub.2-4 alkynyl group, a C.sub.1-4 heteroalkyl group, a C.sub.3-7 cycloalkyl group or a heterocycloalkyl group containing from 3 to 7 ring atoms selected from O, S, C and N.

18. Pharmaceutical composition comprising a compound according to claim 1 and optionally one or more carrier substances and/or one or more adjuvants.

19-21. (canceled)

22. A method for prophylaxis, decolonization and/or treatment of a Staphylococcus aureus infection in a subject which comprises administering to the subject an effective amount of a compound of formula (I): ##STR00478## wherein R.sup.1 is hydrogen, fluorine or a methyl group; R.sup.2 is halogen, OH, NO.sub.2, CN or NH.sub.2; or a C.sub.1-4 alkyl group, a C.sub.2-4 alkenyl group, a C.sub.2-4 alkynyl group, a C.sub.3-5 cycloalkyl group, an OC.sub.3-5 cycloalkyl group, a C.sub.4-8 alkylcycloalkyl group, or a C.sub.1-4 heteroalkyl group; R.sup.4 is an optionally substituted phenyl group; an optionally substituted naphthyl group; an optionally substituted heteroaryl group containing 1 or 2 rings and 5 to 10 ring atoms selected from O, S, N and C; an optionally substituted cycloalkyl aryl group comprising a phenyl group and a cycloalkyl group containing 5 or 6 ring atoms; an optionally substituted heterocycloalkyl aryl group comprising a phenyl group and a heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, B, N and C; an optionally substituted cycloalkyl heteroaryl group comprising a heteroaryl group comprising 5 or 6 ring atoms selected from O, S, N and C and a cycloalkyl group containing or 6 ring atoms; or an optionally substituted heterocycloalkyl heteroaryl group comprising a heteroaryl group comprising 5 or 6 ring atoms selected from O, S, N and C and a heterocycloalkyl group containing 5 or 6 ring atoms selected from O, S, N and C; or an optionally substituted cycloalkyl group containing 1 or 2 rings and 3 to 10 ring atoms; and R.sup.4a is hydrogen; or R.sup.2 and R.sup.4a together are a group of formula O(CH.sub.2).sub.n, wherein n is 1, 2 or 3, wherein the oxygen is bound to the phenyl ring; or of a solvate, a hydrate or a salt thereof.

23-39. (canceled)

40. A compound of formula (I): ##STR00479## wherein R.sup.1 is hydrogen; R.sup.2 is F, Cl, Br, a methyl group, an ethyl group, an iso-propyl group, a NO.sub.2 group, a CF.sub.3 group, a methoxy group, a OCF.sub.3 group, a cyclopropyl group, a CN group, a CD.sub.3 group, a CHF.sub.2 group, a CH.sub.2F group, a CH.sub.2OH group or a NMe.sub.2 group; R.sup.4a is hydrogen; R.sup.4 has the following formula: ##STR00480## wherein M.sup.1 is N or CR.sup.7; M.sup.2 is N or CR.sup.5; M.sup.3 is N or CR.sup.5a; and M.sup.4 is N or CR.sup.7a, R.sup.5 is hydrogen; R.sup.5a is hydrogen, Cl, Br, CN, methyl, methoxy, CF.sub.3, OCF.sub.3, NMe.sub.2, CCH, or SO.sub.2Me; R.sup.6 is an optionally substituted C.sub.3-8 cycloalkyl group, an optionally substituted heterocycloalkyl group containing one or two rings and from 3 to 10 ring atoms selected from O, S, C and N, an optionally substituted phenyl group, an optionally substituted CH.sub.2-phenyl group, an optionally substituted heteroaryl group containing 5 or 6 to 10 ring atoms selected from O, S, N and C or an optionally substituted heterocycloalkyl aryl group comprising a phenyl group and a heterocycloalkyl group containing 4, 5 or 6 ring atoms selected from O, S, N and C; R.sup.7 is hydrogen; and R.sup.7a is hydrogen; or a solvate, a hydrate or a salt thereof.

41-46. (canceled)

47. A method for prophylaxis, decolonization and/or treatment of a Staphylococcus aureus infection in a subject which comprises administering to the subject an effective amount of a compound of formula (I): ##STR00481## wherein R.sup.1 is H, R.sup.2 is Me, R.sup.4a is hydrogen and R.sup.4 is selected from the following groups: ##STR00482## or of a solvate, a hydrate or a salt thereof.

Description

EXAMPLES

Abbreviations and Acronyms

[0108] Abbreviations and Acronyms used in the description of the chemistry and in the Examples that follow are: [0109] aq. aqueous [0110] Ar argon [0111] Boc tert-Butyloxycarbonyl [0112] br. broad [0113] CDCl.sub.3 deuterated chloroform [0114] CD.sub.3OD deuterated methanol [0115] CHCl.sub.3 chloroform [0116] cHex cyclohexane [0117] conc. Concentrated [0118] cpd. compound [0119] CuCl cuprous chloride [0120] Copper (I) iodide cuprous iodide [0121] d doublet [0122] D2O deuterated water [0123] DCM dichloromethane [0124] de-Boc Boc-deprotection [0125] deprot. deprotection [0126] DIPEA Diisopropylethylamine [0127] DME dimethoxyethane [0128] DMSO dimethylsulfoxide [0129] DMSO-d6 deuterated dimethylsulfoxide [0130] ES electrospray [0131] Et.sub.2NH diethylamin [0132] Et.sub.2O diethylether [0133] EtOAc [0134] EtOH [0135] ethyl acetate [0136] ethanol [0137] FA formic acid [0138] FCS fetal calf serum [0139] h hour [0140] HBBS Hanks's Balanced Salt Solution [0141] HCl hydrochloric acid [0142] HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid [0143] HPLC high performance liquid chromatography [0144] H.sub.2O water [0145] H.sub.2SO.sub.4 sulfuric acid [0146] hydrog. hydrogenation [0147] K.sub.2CO.sub.3 potassium carbonate [0148] KOH potassium hydroxide [0149] K.sub.3PO.sub.4 potassium triphosphate [0150] LDH lactate dehydrogenase [0151] m multiplet [0152] MeCN acetonitrile [0153] MeOH methanol [0154] MgSO.sub.4 magnesium sulfate [0155] min minutes [0156] MS mass spectrometry [0157] NaH sodium hydride [0158] NaHCO.sub.3sodium hydrogencarbonate [0159] NaCl sodium chloride [0160] NaOD deuterated sodium hydroxide [0161] NaOH sodium hydroxide [0162] Na.sub.2SO.sub.4 sodium sulfate [0163] Na.sub.2S.sub.2O.sub.4 sodium dithionite [0164] NBS N-bromosuccinimide [0165] NH.sub.3 ammonia [0166] NH.sub.4HCO.sub.3 ammonium bicarbonate [0167] NIS N-Iodsuccinimide [0168] NMR nuclear magnetic resonance [0169] PBS Phosphate Buffered Saline [0170] Pd.sub.2 (dba).sub.3 Tris-(dibenzylidenaceton)-dipalladium(0) [0171] Pd(OAc).sub.2 palladium diacetate [0172] Pd(PPh.sub.3).sub.2Cl.sub.2 Bis(triphenylphosphin)palladium(II)-dichloride [0173] Pd(PPh.sub.3) 4 Tetrakis(triphenylphosphine)palladium(0) [0174] pet-ether petroleum ether [0175] PPh.sub.3 triphenylphosphine [0176] q quartet [0177] quint quintet [0178] rpm rounds per minute [0179] r. t. room temperature [0180] S singlet [0181] sat. saturated [0182] SnCl.sub.2*2H.sub.2O stannous chloride dihydrate [0183] SOCl.sub.2 thionyl chloride [0184] t triplet [0185] TBS tert-butyldimethylsilyl [0186] TFA trifluoroacetic acid [0187] TIPS triisopropylsilyl [0188] UPLC Ultra Performance Liquid Chromatography [0189] wt weight [0190] Xantphos (9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane)

1. Methods of Making the Compounds of Formula (I) of the Present Invention

[0191] In general, the compounds of formula (I) used of the invention might be prepared by standard techniques known in the art, by known processes analogous thereto, and/or by the processes described herein, using starting materials which are either commercially available or producible according to conventional chemical methods. The particular processes to be utilised in the preparation of the compounds of formula (I) of this invention depends upon the specific compound desired. Such factors as the type of substitution at various locations of the molecule and the commercial availability of the starting materials play a role in the path to be followed and in the chosen reaction conditions for the preparation of the specific compounds of formula (I) of this invention. Those factors are readily recognised by one of ordinary skill in the art.

[0192] The following preparative methods are presented to aid the reader in the synthesis of the compounds of the present invention.

2. Experimental Procedures

LC-MS Method

[0193] HPLC-electrospray mass spectra (HPLC ES-MS) were obtained using a Waters Acquity Ultra Performance Liquid Chromatography (UPLC) equipped with a SQ 3100 Mass detector spectrometer. [0194] Column: Acquity UPLC BEH C18 1.7 m, 2.150 mm [0195] Flow: 0.500 mL/min [0196] Eluents: A: H.sub.2O with 0.05% formic acid and B: MeCN with 0.05% formic acid. [0197] Gradient: elution from 5% to 100% B over 3.5 min with an initial hold of 0.5 min and [0198] a final hold at 100% B of 0.5 min. Total run time: 5 min.

[0199] The gradient described could be altered in function of the physico-chemical properties of the compound analysed and is in no way restrictive.

Preparative HPLC Method

[0200] Preparative HPLC was performed using a Waters System consisting of a Waters 2767 Sample Manager, a Waters 2545 Binary Gradient Module, a Waters SFO (System Fluidics Organizer), a Waters 3100 Mass Detector, and a Waters 2498 UV/Visible Detector. [0201] Column: XBridge Prep C18 5 m OBD, 19150 mm [0202] Flow: 20 mL/min [0203] Eluents: A: H.sub.2O with 0.1% TFA and B: MeCN with 0.1% TFA.

[0204] Alternatively, preparative HPLC was performed using a Waters System consisting of 2707 Autosampler and waters 2998 PDA detector supported by Empower Software. LC-MS-electrospray mass spectra (UPLC ES-MS) were obtained using a Waters Acquity Ultra Performance Liquid Chromatography (UPLC) equipped with a SQ detector-2 supported by Masslynx Software. [0205] Column: KROMOSIL-C18 (150*25 MM), 7u [0206] Flow: 25.0 mL/min [0207] Eluents: H.sub.2O with 10 mM NH.sub.4HCO.sub.3 and B: MeCN

[0208] Alternatively, preparative HPLC was performed using an Agilent System consisting of an Agilent Infinity 1260 Autosampler, an Agilent Infinity 1260 Binary Gradient Module, an Agilent 6120 Quadrupole Mass Detector and an Agilent Infinity 1260 DAD VL UV/Visible Detector. [0209] Column: XBridge BEH Prep C18 5 m, 19 mm150 mm [0210] Flow: 32 mL/min [0211] Eluents: A: H.sub.2O with 0.1% TFA and B: MeCN with 0.1% TFA. [0212] General Gradient: elution from X % to Y % B over 20 min with an initial hold of 2 min and a final increase to 100% B over 2 min and hold at 100% B of 2 min followed by a 1 min gradient back to the initial composition. Total run time: 26 min. X=Y30% where Y=concentration of elution for the above described LC-MS method.

[0213] The gradient described could be altered in function of the physico-chemical properties of the compound analyzed and is in no way restrictive.

Accurate Mass method

[0214] High resolution masses were obtained using Maxis II HD mass spectrometer (Bruker).

NMR Methods

[0215] Proton (.sup.1H) nuclear magnetic resonance (NMR) spectra were measured with an Oxford Varian 400/54 (400 MHz) spectrometer or a Bruker Avance II (300 MHz) spectrometer, or with a Bruker Avance III (500 MHz) spectrometer with residual protonated solvent (CHCl.sub.3 7.26; MeOH 3.30; DMSO 2.49) as standard. The NMR data of the synthesized examples are in agreement with their corresponding structural assignments.

2.1 Experimental Examples of the Invention

2.1.1. Synthetic Methods

[0216] ##STR00009##

[0217] The majority of the compounds of the invention were synthesised according to general scheme 1 described above, where M1 is a chlorosulfonylation reaction of a commercially available 6-substituted quinoxaline-2,3 (1H,4H)-dione to give a sulfonyl chloride of formula A. The sulfonamide formation is the coupling step M2 between sulfonyl chloride A and a commercially available aniline derivative to give compounds of formula B. When substituent R.sup.6 is an amine, the non-commercially available anilines E were synthesised from a fluoro- or chloro-nitrobenzene derivative as described in general scheme 2. When substituent R.sup.6 is a halogen, a further Suzuki coupling could be performed to yield biaryls of formula C, where R.sup.6 is an aryl or hereroaryl group, identified by Ar in general scheme 1. Similarly, a Buchwald reaction could be performed to obtain tertiary anilines, as an alternative to what highlighted in general scheme 2. It should be apparent to a person skilled in the art that the sequence of the synthetic steps is dependent on starting materials availability and functional group compatibility and could vary from compound to compound. In particular, steps M2 and M3 could easily be reversed to obtain in a first instance a biarylaniline or a para-substituted dianiline intermediate, which could then be reacted with sulphonyl chlorides A to obtain the final compounds of formula C. Similar conditions as for described methods M2 and M3 can be applied.

##STR00010##

[0218] The following specific examples are presented to illustrate the invention, but they should not be construed as limiting the scope of the invention in any way. In the tables listing the intermediates, the compounds might have characterization such as (M+H).sup.+ mass spectrometry data, HPLC purity and/or NMR. When the route to final compounds C encompasses different reactions steps as those described in General Scheme 1, the Synthetic Procedure is Also Exemplified Below.

2.1.2. Preparation of Intermediate Compounds of Formula (A)

Intermediate 1A-synthesis according to Method 1 (M1)
7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonyl chloride (1A)

##STR00011##

[0219] Chlorosulfonic acid (953 l, 14.2 mmol) was added to 1,4-dihydro-6-methylquinoxaline-2,3-dione (500 mg, 2.8 mmol) and stirred at 100 C. for 1.5 h. The solution was cooled down to r. t. and poured onto ice. The suspension was filtered and then washed with ice-H.sub.2O. The product was dried over night to yield the desired product 1A (509 mg, 95%) as a yellow solid.

[0220] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 11.82 (s, 1H), 11.77 (s, 1H), 7.59 (s, 1H), 6.83 (s, 1H), 2.44 (s, 3H).

[0221] MS (ES) C.sub.9H.sub.7ClN.sub.2O.sub.4S requires: 274, found: 275 (M+H).sup.+, 95%.

[0222] The following sulphonyl chloride intermediates were synthesised in a similar manner as described in Method M1:

TABLE-US-00001 TABLE 1 Sulfonyl chloride intermediates of Formula A [00012] Intermediate R.sub.2 (M + H).sup.+, purity 2A F MS (ES) C.sub.8H.sub.4ClFN.sub.2O.sub.4S requires: 278, found 279 (M + H).sup.+, 96% 3A Cl MS (ES) C.sub.8H.sub.4Cl.sub.2N.sub.2O.sub.4S requires: 294, found 295 (M + H).sup.+, 100% 4A Br MS (ES) C.sub.8H.sub.4ClBrN.sub.2O.sub.4S requires: 340, found 339 (M H).sup., 95% 5A Et MS (ES) C.sub.10H.sub.9ClN.sub.2O.sub.4S requires: 288, found 289 (M + H).sup.+, 94% 6A iPr MS (ES) C.sub.11H.sub.11ClN.sub.2O.sub.4S requires: 302, found 303 (M + H).sup.+, 95% 7A OMe CAS: 959-01-3 8A OCF.sub.3 Crude: ~85% purity by .sup.1H NMR 12A CD.sub.3 Crude: ~80% purity by .sup.1H NMR

[0223] The following sulphonyl chlorides intermediates were synthesised with different methods:

Intermediate 9A

7-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonyl chloride (9A)

##STR00013##

[0224] A stirred mixture of conc. HNO.sub.3 (10 mL, 65%) and conc. H.sub.2SO.sub.4 (20 mL, 96%) was cooled in ice bath below 5 C. 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonyl chloride (1 g, 3.8 mmol) was carefully added keeping the temperature below 5 C. The reaction mixture was stirred for 1 h at 0-5 C. and then for 2 h at r. t. The reaction mixture was poured onto ice and extracted with EtOAc. The combined organic phases were washed with H.sub.2O, sat. NaHCO.sub.3 solution and again H.sub.2O, dried over Na.sub.2SO.sub.4, filtered, and concentrated in vacuo to yield the desired product 9A (750 mg, 65%), which was used in the following step without further purification. .sup.1H NMR (500 MHZ, DMSO-d.sub.6) 12.14 (s, 1H), 12.08 (s, 1H), 7.65 (s, 1H), 7.26 (s, 1H).

Intermediate 10A

5-fluoro-7-methylquinoxaline-2,3 (1H,4H)-dione (10D)

[0225] ##STR00014##

[0226] 3-fluoro-5-methyl-benzene-1,2-diamine (200 mg, 1.40 mmol) was added to an oven-dried microwave vial, followed by diethyl oxalate (2 mL) and the mixture was heated to 185 C. for 4 h. The reaction was allowed to cool down to r. t., diluted with of Et.sub.2O, the obtained solids were filtered, washed with Et.sub.2O and dried on air to afford the desired product (D) (169 mg, 61%) as a brown solid.

[0227] .sup.1H NMR (300 MHZ, DMSO-d.sub.6) 11.94 (s, 2H), 6.84 (d, J=11.6 Hz, 1H), 6.72 (s, 1H), 2.26 (s, 3H).

[0228] MS (ES) C.sub.9H.sub.7FN.sub.2O.sub.2 requires: 194, found: 195 (M+H).sup.+, 95%.

5-fluoro-7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonyl chloride (10A)

[0229] ##STR00015##

[0230] Intermediate 10D (100 mg, 0.515 mmol) was added to an oven-dried microwave vial followed by chlorosulfonic acid (0.35 mL), and the mixture was heated to 65 C. for 16 h. Thionyl chloride (123 mg, 1.03 mmol) was then added to the reaction mixture and further stirred at 65 C. for 5 h. The reaction mixture was poured onto to an ice-H.sub.2O and the precipitated solids were collected by filtration, washed with H.sub.2O and then dried on air to give the corresponding product as a mixture of isomers: 26% of desired compound (10A) (minor isomer) and 73% of the undesired product (11A) (major isomer). The mixture was used in the following step without attempt at separating the regioisomers.

5-fluoro-2,3-dihydroxy-7-methyl-quinoxaline-6-sulfonyl chloride (minor isomer-desired product)

[0231] .sup.1H NMR (300 MHZ, DMSO-d.sub.6) 12.73 (s, 2H), 6.64 (s, 1H), 2.47 (s, 3H). MS (ES) C.sub.11H.sub.12FN.sub.3O.sub.4S requires: 301, found: 302 (M+H).sup.+, 30% (derivatization was used for LC/MS measurement to avoid hydrolysis. The compound was converted into dimethyl sulfonamide (M+H.sup.+=301)).

8-Fluoro-2,3-dihydroxy-6-methyl-quinoxaline-5-sulfonyl chloride (major isomer-undesired product)

[0232] .sup.1H NMR (300 MHZ, DMSO-d.sub.6) 11.93 (s, 2H), 6.92 (d, J=11.8 Hz, 1H), 2.54 (s, 3H). MS (ES) C.sub.11H.sub.12FN.sub.3O.sub.4S requires: 301, found: 302 (M+H).sup.+, 68% (derivatization was used for LC/MS measurement to avoid hydrolysis. The compound was converted into dimethyl sulfonamide (M+H.sup.+=301)).

Synthesis of Deuterated Intermediate 12D

[0233] Deuterated building block 12D was synthesised according to scheme 3:

##STR00016##

6-(Bromomethyl)-2,3-dimethoxyquinoxaline (E)

[0234] ##STR00017##

[0235] A mixture of 2,3-dimethoxy-6-methylquinoxaline (2.8 g, 13.7 mmol), NBS (2.7 g, 15.1 mmol) and benzoyl peroxide (350 mg, 25% H.sub.2O) in absolute CHCl.sub.3 without stabilizer (90 mL) was heated under reflux for 16 h. The reaction was allowed to cool down to r. t. and the solvents were reduced in vacuo. The residue was purified by column chromatography on silica gel using a gradient of EtOAc in pet-ether to yield the desired product (E) (2.78 g, 72%) as a white solid.

[0236] MS (ES) C.sub.11H.sub.11BrN.sub.2O.sub.2 requires: 282/284, found: 283/285 (M+H).sup.+, 90%.

((2,3-Dimethoxyquinoxalin-6-yl)methyl)triphenylphosphonium bromide (F)

[0237] ##STR00018##

[0238] A mixture of 6-(bromomethyl)-2,3-dimethoxyquinoxaline (E) (2.8 g, 9.8 mmol) and PPh.sub.3 (2.6 g, 9.8 mmol) in toluene (20 mL) was heated at reflux for 4 h The reaction was allowed to cool down to r. t. and the solid was collected by filtration, washed with toluene and dried under vacuum at 50 C. to yield the desired compound (F) (4.1 g, 77%) as a white solid.

[0239] .sup.1H NMR (700 MHZ, DMSO-d.sub.6): 7.93-7.89 (m, 3H), 7.77-7.68 (m, 12H), 7.58 (d, J=8.4 Hz, 1H), 7.43 (t, J=2.0 Hz, 1H), 7.05 (dt, J=8.4, 2.0 Hz, 1H), 5.35 (d, J.sub.P-H=15.6 Hz, 2H), 4.01 (s, 3H), 3.96 (s, 3H). Purity: 90%.

2,3-Dimethoxy-6-(methyl-d.SUP.3.) quinoxaline (G)

[0240] ##STR00019##

[0241] To a solution of ((2,3-dimethoxyquinoxalin-6-yl)methyl)triphenylphosphonium bromide (F) (4.1 g, 7.5 mmol) in THF (20 mL) was added a solution of NaOD in D20 (10 mL, w/w %). The reaction mixture was stirred at 25 C. for 18 h. EtOAc and H.sub.2O were added to the reaction mixture. The organic layer was separated, dried over Na.sub.2SO.sub.4 and reduced in vacuo. The residue was purified by column chromatography in pet-ether to yield the desired product (G) (1.08 g, 69%) as a white solid.

[0242] MS (ES) C.sub.11H.sub.9D3N.sub.2O.sub.2 requires: 207, found: 208 (M+H).sup.+, 95%.

6-(Methyl-d.SUP.3.)-1,4-dihydroquinoxaline-2,3-dione (12D)

[0243] ##STR00020##

[0244] 2 M HCl (15 mL) was added to a solution of 2,3-dimethoxy-6-(methyl-d.sup.3) quinoxaline (G) in dioxane, and the reaction was heated at 80 C. for 16 h. The mixture was allowed to cool down to r. t. and dioxane was reduced in vacuo. The resulting precipitate was filtered, washed with water and dried in vacuo to yield the desired product 12D (847 mg, 90%) as a white solid.

[0245] MS (ES) C.sub.9H.sub.5D3N.sub.2O.sub.2 requires: 179, found: 180 (M+H).sup.+, 99%.

Intermediate 1B-Synthesis According to Method 2a (M2a)

N-(4-bromo-3-chlorophenyl)-7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (75-1B)

[0246] ##STR00021##

[0247] To a mixture of sulfonyl chloride 1A (327 mg, 1.19 mmol) in dry pyridine (1.2 mL) 4-bromo-3-chloroanilin (270 mg, 1.31 mmol) was added and stirred at r. t. After 1.5 h the mixture was diluted with a 1M aq. HCl solution and extracted with DCM. The combined organic phases were dried on MgSO.sub.4, filtered and evaporated in vacuo. The crude product was purified by flash chromatography on silica gel using a gradient of EtOAc in cHex to yield the desired product (75-1B) (272 mg, 100%) as a light brown solid. .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 12.05 (s, 1H), 11.90 (s, 1H), 10.80 (s, 1H), 7.70 (s, 1H), 7.58 (d, J=8.7 Hz, 1H), 7.23 (d, J=2.5 Hz, 1H), 6.97 (s, 1H), 6.91 (dd, J=8.8, 2.6 Hz, 1H), 2.48 (s, 3H).

[0248] MS (ES) C.sub.15H.sub.11BrClN.sub.3O.sub.4S requires: 445, found: 446 (M+H).sup.+, 100%

Compound 222-synthesis according to Method 2 (M2b) 7-methyl-2,3-dioxo-N-(5-(trifluoromethoxy)pyridin-2-yl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (222)

[0249] ##STR00022##

[0250] Sulfonyl chloride 1A (30 mg, 0.109 mmol) and 5-(trifluoromethoxy)pyridin-2-amine (23.3 mg, 0.131 mmol) were dissolved in dry THF (1.6 mL). NaH (60% in mineral oil, 21.8 mg, 0.546 mmol) was added at once and the mixture was and stirred at r. t. for 1 h. The mixture was diluted with a sat. NH.sub.4Cl aq. solution, extracted with EtOAc and washed with H.sub.2O. The combined organic phases were dried on MgSO.sub.4, filtered and evaporated in vacuo. The crude product was purified by preparative HPLC using a gradient of MeCN in H.sub.2O with 0.1% TFA to yield the desired product (222) (16.2 mg, 37%) as a white powder.

[0251] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 12.09 (s, 1H), 11.95 (s, 1H), 11.63 (s, 1H), 8.36 (s, 1H), 7.84 (s, 1H), 7.15 (s, 1H), 6.99 (s, 1H), 2.52 (s, 3H).

[0252] MS (ES) C.sub.15H.sub.11F3N.sub.4O.sub.5S requires: 416, found: 417 (M+H).sup.+, 100%

Compound 1C-Synthesis According to Method 3 (M3)

N-(2-chloro-4-fluoro-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (3-1C)

[0253] ##STR00023##

[0254] Intermediate 1B (30.0 mg, 0.067 mmol), 4-fluorophenylboronic acid (18.9 mg, 0.135 mmol), K.sub.2CO.sub.3 (18.6 mg; 0.135 mmol) and Pd(PPh.sub.3) 4 (1.56 mg, 0.0013 mmol) were suspended in DME/H.sub.2O (2:1, 2 mL) and heated at 120 C. for 1.5 h in a microwave. After cooling to r. t., the mixture was filtered and evaporated in vacuo. The crude product was purified by reverse phase flash chromatography on C18 using a gradient of MeCN in H.sub.2O to yield the desired product (3-1C) (8.8 mg, 28%) as a white solid. .sup.1H NMR (300 MHZ, DMSO-d.sub.6) 12.13 (s, 1H), 11.99 (s, 1H), 10.86 (s, 1H), 7.81 (s, 1H), 7.38 (ddd, J=8.6, 5.5, 2.6 Hz, 2H), 7.34-7.17 (m, 4H), 7.09 (dd, J=8.4, 2.3 Hz, 1H), 7.03 (s, 1H), 2.55 (s, 3H).

[0255] MS (ES) C21H.sub.15ClFN.sub.3O.sub.4S requires: 459, found: 458 MH.sup.+, 100%.

Synthesis of 2,3-Dioxo-N-(4-(trifluoromethoxy)phenyl)-7-trifluoromethyl-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (190)

4-Amino-5-nitro-2-(trifluoromethyl)benzenesulfonyl chloride (1E)

[0256] ##STR00024##

[0257] 2-Nitro-5-(trifluoromethyl) aniline (1.0 g, 4.9 mmol) was added to chlorosulfonic acid (10 mL) at r. t. The reaction mixture was stirred for 5 h at 115 C., upon which it was allowed to cool down to r. t. and was poured onto ice. The aq. layer was extracted with EtOAc. The combined organic phases were washed with H.sub.2O, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo to yield the crude product (1E), which was used in the following step without further purification.

4-Amino-5-nitro-N-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)benzenesulfonamide (1F)

[0258] ##STR00025##

[0259] 4-(trifluoromethoxy) aniline (1.8 g, 10.2 mmol) was reacted with crude sulfonyl chloride D according to method M2 to yield the desired product (1F) (724 mg, 33% over 2 steps).

[0260] .sup.1H NMR (500 MHZ, DMSO-d.sub.6) 10.66 (s, 1H), 8.64 (s, 1H), 8.32 (br. s, 2H), 7.61 (s, 1H), 7.28 (d, J=8.6 Hz, 2H), 7.18 (d, J=8.6 Hz, 2H). MS (ES) C14H.sub.10F6N.sub.3O.sub.5S requires: 445, found: 446 (M+H).sup.+.

4,5-Diamino-N-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)benzenesulfonamide (1G)

[0261] ##STR00026##

[0262] To a solution of intermediate 1F (700 mg, 1.57 mmol) in EtOH (10 mL) was added SnCl.sub.2*2H.sub.2O (1.1 g, 5 mmol) and conc. HCl (17 mL). The reaction mixture was stirred for 30 min at 75 C. and cooled to r. t. pH-value was adjusted to 13-14 using 40% aq. KOH. The mixture was extracted with EtOAc, and the combined organic phases were dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo to yield the desired product 1G (660 mg, 100%), which was used in the following step without further purification.

[0263] MS (ES) C14H.sub.12F.sub.6N.sub.3O.sub.3S requires: 415, found: 416 (M+H).sup.+.

2,3-Dioxo-N-(4-(trifluoromethoxy)phenyl)-7-trifluoromethyl-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (190)

[0264] ##STR00027##

[0265] To a suspension of the crude dianiline 1G (660 mg, ca. 1.57 mmol) in HCl (4 N, 10 mL) was added oxalic acid (180 mg, 2 mmol) and HCl (4 N, 5 mL). The mixture was stirred at 130 C. for 2.5 h, upon which it was allowed to cool down to r. t. The mixture was extracted with EtOAc, and the combined organic phases were dried over Na.sub.2SO.sub.4, filtered, and concentrated in vacuo. The residue was purified by two subsequent column chromatographies: the first column on silica gel using a gradient of MeOH in DCM, the second on reverse phase C18 silica using a gradient of MeCN in H.sub.2O to yield the desired product (190) (100 mg, 13% over 2 steps).

[0266] .sup.1H NMR (500 MHZ, DMSO-d.sub.6) 12.27 (br. s, 2H), 10.87 (s, 1H), 7.86 (s, 1H), 7.59 (s, 1H), 7.29 (d, J=8.9 Hz, 2H), 7.18 (d, J=8.9 Hz, 2H). HRMS (ESI) calcd. for C16H.sub.10F.sub.6N.sub.3O.sub.5S (M+H).sup.+ 470.0245, found 470.0241.

Synthesis of 7-Cyclopropyl-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (194)

2-Bromo-4-fluoro-5-nitroaniline (H)

[0267] ##STR00028##

[0268] 2-Bromo-4-fluoroaniline (3.0 g, 15.8 mmol) was carefully added to conc. H.sub.2SO.sub.4 (30 mL), and the mixture was stirred at 30 C. for 1 h. The reaction mixture was cooled to 5-10 C. (ice/NaCl bath) and KNO.sub.3 (1.7 g, 16.6 mmol) was added in batches. The reaction mixture was stirred at 0 C. for 3 h, poured into ice-H.sub.2O and extracted with EtOAc. The combined organic phases were washed with aq. NaHCO.sub.3 and H.sub.2O, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel using a gradient of EtOAc in petroleum ether to yield the desired product (H) (2.2 g, 59%).

[0269] MS (ES) C6H.sub.5BrFN.sub.2O.sub.2 requires: 234/236, found: 235/237 (M+H).sup.+.

2-Cyclopropyl-4-fluoro-5-nitroaniline (J)

[0270] ##STR00029##

[0271] A mixture of bromo derivative H (1.2 g, 5 mmol), cyclopropyl boronic acid (560 mg, 6.5 mmol), Pd(OAc).sub.2 (113 mg, 0.5 mmol, 10%), tricyclohexylphosphine (210 mg, 1 mmol) and K.sub.3PO.sub.4 (3.7 g, 17.5 mmol) was evacuated and backfilled with Ar three times, then H.sub.2O (2 mL) and toluene (24 mL) were added. The mixture was further degassed with Ar and stirred at 100 C. for 12 h under Ar atmosphere, upon which it was allowed to cool down to r. t. EtOAc was added, and the organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel using a gradient of EtOAc in petroleum ether to yield the desired product (J) (687 mg, 70%). .sup.1H NMR (500 MHZ, DMSO-d.sub.6): 7.30 (d, J.sub.H-F=6.8 Hz, 1H), 6.89 (d, J.sub.H-F=12.8 Hz, 1H), 5.53 (s, 2H), 1.85-1.76 (m, 1H), 1.00-0.93 (m, 2H), 0.71-0.63 (m, 2H). .sup.19F NMR (470 MHZ, DMSO-d.sub.6) -135.29.

2-Cyclopropyl-4-fluoro-5-nitrobenzenesulfonyl chloride (K)

[0272] ##STR00030##

[0273] In a first flask, intermediate J (687 mg, 3.5 mmol) was dissolved in conc. HCl (8 mL), and the resulting solution was cooled to 5 C., using an ice/NaCl bath. A solution of sodium nitrite (276 mg, 4 mmol) in distilled H.sub.2O (5 mL) was added in portions with stirring, while maintaining the temperature below 0 C. The mixture was then kept at this temperature. In a second flask, SOCl.sub.2 (1.8 mL, 3 g, 25 mmol) was added dropwise to distilled H.sub.2O (12 mL), which had been pre-cooled to 5 C. using an ice/NaCl bath. The resulting solution was allowed to warm to r. t., CuCl (50 mg, 0.5 mmol) was added, and the reaction mixture was re-cooled to 5 C. With continued cooling and stirring, the contents of the first flask were added in small portions to the contents of the second flask, and the mixture was stirred for 1 h at 5 C. The mixture was then extracted with EtOAc, and the combined organic phases were dried over Na.sub.2SO.sub.4, filtered, and concentrated in vacuo, to yield the desired product (K) (860 mg, 88%), which was used in the following step without further purification or characterization.

2-Cyclopropyl-4-fluoro-5-nitro-N-(4-(trifluoromethoxy)phenyl) benzenesulfonamide (L)

[0274] ##STR00031##

[0275] 4-(trifluoromethoxy) aniline (549 mg, 3.1 mmol) was reacted with crude sulfonyl chloride J (860 mg, 3.1 mmol) according to method M2 to yield the desired product (L) (697 mg, 54%).

[0276] .sup.1H NMR (500 MHZ, DMSO-d.sub.6): 11.04-10.88 (br. s, 1H), 8.56 (d, J.sub.H-F=7.7 Hz, 1H), 7.26 (d, J=9.2 Hz, 2H), 7.24 (d, J.sub.H-F=13.0 Hz, 1H), 7.18 (d, J=9.2 Hz, 2H), 2.79-2.69 (m, 1H), 1.25-1.20 (m, 2H), 1.01-0.96 (m, 2H).

[0277] .sup.19F NMR (470 MHZ, DMSO-d.sub.6) -57.10.

4-Amino-2-cyclopropyl-5-nitro-N-(4-(trifluoromethoxy)phenyl) benzenesulfonamide (2F)

[0278] ##STR00032##

[0279] Sat. aq. NH.sub.3 (10 mL) was added to the solution of fluoro derivative L (697 mg, 1.66 mmol) in EtOH (5 mL) at r. t. The mixture was stirred at r. t. overnight. The solvent was removed under reduced pressure and the mixture was extracted with EtOAc, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel using a gradient of EtOAc in pet-ether to yield the desired product (2F) (390 mg, 56%). .sup.1H NMR (500 MHZ, DMSO-d.sub.6) 10.57 (s, 1H), 8.53 (s, 1H), 7.76 (s, 2H), 7.26 (d, J=9.2 Hz, 2H), 7.15 (d, J=9.2 Hz, 2H), 6.57 (s, 1H), 2.57-2.51 (m, 1H), 1.15-1.09 (m, 2H), 0.68-0.63 (m, 2H). .sup.19F NMR (470 MHZ, DMSO-d.sub.6) 57.09.

[0280] MS (ES) C16H.sub.15F.sub.3N.sub.3O.sub.5S requires: 417, found: 418 (M+H).sup.+.

4,5-Diamino-2-cyclopropyl-N-(4-(trifluoromethoxy)phenyl) benzenesulfonamide (2G)

[0281] ##STR00033##

[0282] To a solution of nitro derivative 2F (390 mg, 0.94 mmol) in dioxane (12 mL) at 10 C. was added a suspension of SnCl.sub.2*2H.sub.2O (1.05 g, 4.68 mmol) in conc. HCl (2 mL). The mixture was stirred for 6.5 h at r. t., neutralized with 40% NaOH and extracted with EtOAc. The combined organic phases were dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo to yield the desired product (2G) (464 mg, 27% excess wt), which was used in the following step without further purification.

[0283] MS (ES) C16H.sub.17F.sub.3N.sub.3O.sub.5S requires: 387, found: 388 (M+H).sup.+.

7-Cyclopropyl-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (194)

[0284] ##STR00034##

[0285] The crude product dianiline 2G (232 mg, ca. 0.47 mmol) was dissolved in diethyl oxalate (2 mL). The mixture was heated to 120 C. and stirred for 2 h. The reaction mixture was allowed to cool to r. t. and separated by two subsequent column chromatographies: the first column on silica gel using a gradient of MeOH in DCM, the second on reverse phase C18 silica using a gradient of MeCN in H.sub.2O to yield the desired product (194) (43 mg, 21%).

[0286] .sup.1H NMR (500 MHZ, DMSO-d.sub.6) 11.93 (s, 1H), 11.90 (s, 1H), 10.64 (s, 1H), 7.76 (s, 1H), 7.26 (d, J=9.1 Hz, 2H), 7.14 (d, J=9.1 Hz, 2H), 6.71 (s, 1H), 2.63-2.55 (m, 1H), 1.10-1.04 (m, 2H), 0.60-0.55 (m, 2H). .sup.19F NMR (470 MHZ, DMSO-d.sub.6) -57.08.

[0287] MS (ES) C18H.sub.15F.sub.3N.sub.3O.sub.5S requires: 441, found: 442 (M+H).sup.+.

Intermediate 1N-synthesis according to Method 4 (M4) 4-(2-chloro-4-nitrophenyl) morpholine (1N)

[0288] ##STR00035##

[0289] Morpholine (100 L, 1.14 mmol) and 2-chloro-1-fluoro-4-nitrobenzene (100 mg, 0.570 mmol) were dissolved in DMSO (1 mL), and K.sub.2CO.sub.3 (157 mg, 1.14 mmol) was added. The mixture was shaken at 105 C. for 5.5 h, followed by cooling down to r. t. The mixture was diluted with H.sub.2O and extracted with EtOAc. The combined organic phases were dried on MgSO.sub.4, filtered and evaporated in vacuo. The crude product was purified by flash chromatography on silica gel using a gradient of EtOAc in cHex to yield the desired product (1N) (114 mg, 82%) as a yellow solid.

[0290] MS (ES) C10H.sub.11ClN2O.sub.3 requires: 242, found: 243 (M+H).sup.+, 100%.

Intermediate 1Q-synthesis according to Method 5 (M5) 3-chloro-4-morpholinoaniline (1Q)

[0291] ##STR00036##

[0292] Nitro-derivative 1N (96 mg, 0.396 mmol) was dissolved in EtOH (6 mL), and Fe (110 mg, 1.978 mmol) was added, followed by a 2 M HCl solution (1 mL). The mixture was stirred at 100 C. for 1 h, and allowed to cool down to r. t. The mixture was diluted with EtOAc and washed with a sat. NaHCO.sub.3 solution. The aqueous phase was extracted once more with EtOAc, and the combined organic phases were dried on MgSO.sub.4, filtered over celite and evaporated in vacuo to yield the desired product (1Q) (83 mg, 99%) as a brown powder.

[0293] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 6.89 (dd, J=8.6, 0.8 Hz, 1H), 6.63 (dd, J=2.5, 0.8 Hz, 1H), 6.49 (ddd, J=8.6, 2.6, 0.9 Hz, 1H), 5.04 (s, 2H), 3.73-3.64 (m, 4H), 2.83-2.75 (m, 4H).

[0294] MS (ES) C10H.sub.13ClN2O requires: 212, found: 213 (M+H).sup.+, 96%.

[0295] The following anilines intermediates were synthesised in a similar manner as described in Method M4 and M5:

TABLE-US-00002 TABLE 1a Anilines intermediates of Formula Q [00037] Intermediate R9-N-R8 (M + H).sup.+ 2Q [00038] MS (ES): C.sub.11H.sub.15ClN.sub.2O requires: 226, found: 227 (M + H).sup.+. 3Q [00039] MS (ES): C.sub.11H.sub.15ClN.sub.2O requires: 226, found: 227 (M + H).sup.+. 4Q [00040] MS (ES): C.sub.11H.sub.15ClN.sub.2O requires: 226, found: 227 (M + H).sup.+. 5Q [00041] MS (ES): C.sub.10H1.sub.3ClN.sub.2 requires: 196, found: 197 (M + H).sup.+. 6Q [00042] MS (ES): C.sub.12H.sub.17ClN.sub.2O requires: 240, found: 241 (M + H).sup.+.

4-amino-2-fluoro-5-nitrobenzenesulfonyl chloride (3E)

[0296] ##STR00043##

[0297] 5-fluoro-2-nitroaniline (2.00 g, 12.8 mmol) was added portionwise to chlorosulfonic acid (10 mL). After stirring for 4 h at 120 C. the solution was cooled down to 0 C. and poured onto ice-H.sub.2O. The mixture was extracted with EtOAc. The combined organic phases were dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo to yield the desired product (3E) (2.95 g, 90%) as a brown oil.

[0298] .sup.1H-NMR (500 MHZ, DMSO-d.sub.6) 8.28 (d, .sup.4J.sub.H-F=7.5 Hz, 1H), 6.68 (d, .sup.3J.sub.H-F=11.8 Hz, 1H).

4-amino-2-fluoro-5-nitro-N-(4-(trifluoromethoxy)phenyl) benzenesulfonamide (3F)

[0299] ##STR00044##

[0300] Dry pyridine (1.4 mL, 17.3 mmol) was added to a solution of 4-(trifluoromethoxy)-aniline (1.55 mL, 11.6 mmol) in dry DCM (10 mL) under Ar atmosphere. A solution of intermediate 3E (2.95 g, 11.6 mmol) in dry DCM (40 mL) was added over a period of 20 min at 0 C. using a metal cannula. The reaction mixture was allowed to warm to r. t. and stirred for 13 h. The solvents were reduced in vacuo and H.sub.2O was added to the residue and the mixture was extracted with EtOAc. The combined organic phases were dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. The crude was purified by flash chromatography on silica gel using a gradient of acetone in DCM, followed by recrystallization using a mixture of acetone and DCM to yield the desired product (3F) (1.66 g, 36%) as yellow needles.

[0301] .sup.1H-NMR (500 MHZ, DMSO-d.sub.6) 10.75 (s, 1H), 8.41 (d, .sup.4J.sub.H-F=7.6 Hz, 2H), 8.15 (br. s, 2H), 7.29 (m, 2H), 7.19 (m, 2H), 6.82 (d, .sup.3J.sub.H-F=12.4 Hz, 1H). MS (ES) C13H.sub.9F.sub.4N.sub.3O.sub.5S requires: 395, found 396 (M+H).sup.+.

7-amino-8-nitro-2-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepine 1,1-dioxide (R)

[0302] ##STR00045##

[0303] Intermediate 3F (400 mg, 1.01 mmol) was dissolved in dry DMF (12 mL) and added to previously in vacuo flame dried K.sub.2CO.sub.3 (442 mg, 3.20 mmol) under Ar atmosphere. 2-Iodoethanol (0.7 mL, 8.96 mmol) was added and the reaction mixture was stirred for at 50 C. for 24 h. The solvents were reduced in vacuo. After addition of H.sub.2O the pH of the mixture was adjusted to 4 with 1 M HCl. The precipitated solid was dissolved in EtOAc, and the mixture was washed with a half-saturated NaCl solution. The organic phase was dried, filtered, and reduced in vacuo to yield the alkylated intermediate. The latter was dissolved in dry DMF (5 mL) and Cs.sub.2CO.sub.3 (658 mg, 2.02 mmol) was added. The reaction mixture was stirred at 80 C. for 6 h, upon which the solvent was reduced in vacuo. H.sub.2O was added and the pH of the mixture was adjusted to 6 with 1 M HCl. The precipitated solid was dissolved in EtOAc and the organic phase washed with half-saturated NaCl solution. The organic phase was dried over Na.sub.2SO.sub.4, filtered, and the solvent reduced in vacuo. The crude was purified by flash chromatography on silica gel using a gradient of EtOAc in petroleum ether to yield the desired product (R) (326 mg, 77%) as a yellow solid.

[0304] .sup.1H-NMR (700 MHZ, DMSO-d.sub.6) 8.24 (s, 1H), 8.05 (br. s, 2H), 7.37 (s, 4H), 6.81 (s, 1H), 4.37 (m, 2H), 4.06 (m, 2H).

[0305] MS (ES) C15H.sub.12F.sub.3N.sub.3O.sub.6S requires: 419, found 420 (M+H).sup.+.

7,8-diamino-2-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepine 1,1-dioxide(S)

[0306] ##STR00046##

[0307] Intermediate R (150 mg, 0.357 mmol) was dissolved in dioxane (5 mL) and conc. NH.sub.3 solution (0.6 mL) was added. Na.sub.2S.sub.2O.sub.4 (790 mg, 4.54 mmol) was dissolved in H.sub.2O (8 mL) and added dropwise to the reaction solution. After stirring for 4.5 h at r. t., the organic solvents were reduced in vacuo and H.sub.2O was added. The pH of the aq. phase was adjusted to 6 with 1 M HCl and the latter was extracted with EtOAc. The combined organic phases were dried over Na.sub.2SO.sub.4, filtered, and reduced in vacuo to yield the desired product(S) (111 mg, 80%) as a beige solid.

[0308] .sup.1H-NMR (500 MHZ, DMSO-d.sub.6) 7.35 (m, 2H), 7.27 (m, 2H), 6.79 (s, 1H), 6.36 (s, 1H), 5.48 (br. s, 2H), 4.68 (br. s, 2H), 4.08 (m, 2H), 4.00 (m, 2H).

[0309] MS (ESI) C15H.sub.14F.sub.3N.sub.3O.sub.4S requires: 389, found 390 (M+H).sup.+.

2-(4-(trifluoromethoxy)phenyl)-3,4,7,10-tetrahydro-2H-[1,4,5]oxathiazepino[2,3-glquinoxaline-8,9-dione 1,1-dioxide (237)

[0310] ##STR00047##

[0311] A mixture of dianiline S (110 mg, 0.283 mmol) and dimethyl oxalate (1.57 g, 13.3 mmol) was stirred at 120 C. for 4 h, upon which the it was allowed to cool down to r. t. and dissolved in MeOH. The solvents were reduced in vacuo and the residue was purified by preparative HPLC using a gradient of MeCN in H.sub.2O to yield the desired product (237) (104 mg, 83%) as a white solid.

[0312] .sup.1H-NMR (500 MHZ, DMSO-d.sub.6) 12.07 (br. s, 1H), 11.97 (br. s, 1H), 7.42 (s, 1H), 7.35 (m, 2H), 7.29 (m, 2H), 6.99 (s, 1H), 4.29 (m, 2H), 4.09 (mc, 2H). MS (ESI) C17H.sub.12F.sub.3N.sub.3O.sub.6S requires: 443, found 444 (M+H).sup.+.

[0313] Dimethylamine derivative 221 was also synthesized from intermediate 3F using the procedure described below.

4-amino-2-(dimethylamino)-5-nitro-N-(4-(trifluoromethoxy)phenyl) benzenesulfonamide (4F)

[0314] ##STR00048##

[0315] Intermediate 3F (182 mg, 0.460 mmol) was dissolved in dry DMF (5 mL) and DIPEA (280 L, 1.65 mmol) was added, followed by a 2 M N, N-dimethylamine solution in THF (500 L, 1 mmol). The solution was stirred at 100 C. for 4 h and the solvent was removed in vacuo. The residue was dissolved in EtOAc and washed with H.sub.2O. The organic layer was dried over Na.sub.2SO.sub.4, filtered, and reduced in vacuo. The residue was purified by flash chromatography on silica gel using a gradient of EtOAc in petroleum ether to yield the desired product 4F (188 mg, 97%) as a yellow solid.

[0316] .sup.1H-NMR (500 MHZ, DMSO-d.sub.6) 10.26 (s, 1H), 8.50 (s, 1H), 7.73 (br. s, 2H), 7.22 (mc, 2H), 7.11 (mc, 2H), 6.51 (s, 1H), 2.74 (s, 6H).

[0317] MS (ESI) C15H.sub.15F.sub.3N.sub.4O.sub.5S requires: 420, found 421 (M+H).sup.+.

4,5-diamino-2-(dimethylamino)-N-(4-(trifluoromethoxy)phenyl) benzenesulfonamide (4G)

[0318] ##STR00049##

[0319] Intermediate 4F (93.3 mg, 0.222 mmol) was dissolved in 2.5 mL 1,4-dioxane and conc. aq. NH.sub.3 solution (0.3 mL, ca. 33%) was added. Na.sub.2S.sub.2O.sub.4 (445 mg, 2.56 mmol) was dissolved in deionized H.sub.2O (4 mL) and added dropwise to the starting material. The mixture was stirred for 3 h at r. t., upon which the organic solvents were reduced in vacuo. The pH value was adjusted to 6 with 1 M HCl. The precipitated solid was extracted with EtOAc, and the combined organic layers were dried over Na.sub.2SO.sub.4, filtered and reduced in vacuo to yield the desired product 4G (77.2 mg, 89%) as a pale pink solid, which was used in the following step without further purification.

[0320] .sup.1H-NMR (500 MHZ, DMSO-d.sub.6) 9.59 (br. s, 1H), 7.17 (mc, 4H), 7.01 (s, 1H), 6.49 (s, 1H), 5.24 (s, 2H), 4.64 (s, 2H), 2.47 (s, 6H).

[0321] MS (ESI) C15H.sub.17F.sub.3N.sub.4O.sub.3S requires: 390, found 391 (M+H).sup.+.

[0322] The following dianilines intermediates were synthesised in a similar manner as described for intermediate 4G. Reaction conditions and bases employed were dependent on functional group compatibility and operator, and could vary from compound to compound, as should be apparent to a person skilled in the art.

TABLE-US-00003 TABLE 1b dianilines intermediates of Formula G [00050] Intermediate R.sup.2 (M + H).sup.+ 5G [00051] MS (ES): C.sub.15H.sub.16F.sub.3N.sub.3O.sub.4S requires: 391, found: 392 (M + H).sup.+. 6G [00052] MS (ES): C.sub.15H.sub.13F.sub.6N.sub.3O.sub.4S requires: 445, found: 446 (M + H).sup.+. 7G [00053] MS (ES): C.sub.14H.sub.15F.sub.3N.sub.4O.sub.3S requires: 376, found: 377 (M + H).sup.+. 8G [00054] MS (ES): C.sub.15H.sub.17F.sub.3N.sub.4O.sub.4S requires: 406, found: 407 (M + H).sup.+. 9G [00055] MS (ES): C.sub.16H.sub.16F.sub.3N.sub.3O.sub.4S requires: 403, found: 404 (M + H)+

7-(dimethylamino)-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (221)

[0323] ##STR00056##

[0324] Dianiline 4G (77.2 mg, 0.198 mmol) and 1,1-oxalyldiimidazole (49.8 mg, 0.262 mmol), were dissolved in dry THF (5 mL) under Ar atmosphere. After stirring for 2 h at 50 C., additional 1,1-oxalyldiimidazole (19.4 mg, 102 mol) was added to the reaction. The solution was stirred for 1 h at 50 C., upon which the volatiles were removed in vacuo and the residue purified by reverse phase chromatography on C18 using a gradient of MeCN in H.sub.2O, to yield the desired product 221 (49.6 mg, 56%) as a white solid.

[0325] .sup.1H-NMR (500 MHZ, DMSO-d.sub.6) 11.98 (s, 1H), 11.93 (s, 1H), 10.13 (s, 1H), 7.68 (s, 1H), 7.24-7.20 (m, 2H), 7.20-7.17 (m, 2H), 7.08 (s, 1H), 2.56 (s, 6H).

[0326] MS (ESI) C17H.sub.15F.sub.3N.sub.4O.sub.5S requires: 444, found 445 (M+H).sup.+.

[0327] An exemplified hydrogenation procedure to obtain compound 306 from compound 299 is described below. A similar procedure was employed to reduce compound 274 to 284 and compound 297 to compound 304.

N-(3-bromo-4-cyclohexylphenyl)-7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (306)

[0328] ##STR00057##

[0329] To a stirred solution of 299 (150 mg, 0.30 mmol) in MeOH was added 10% PtC(300 mg) and the mixture was stirred at RT for 16 h under H.sub.2 balloon atmosphere. The suspension was filtered through a celite pad and the pad was washed with MeOH. The filtrate was concentrated under reduced pressure and the crude product was purified by prep HPLC by using NH.sub.4HCO.sub.3 in H.sub.2O: acetonitrile as an eluent. The compound containing fractions were concentrated and dried to yield the desired product 306 (22 mg, 14%) as an off-white solid.

[0330] .sup.1H NMR (400 MHZ, DMSO) : 12.08 (s, 1H), 11.95 (s, 1H), 10.56 (s, 1H), 7.74 (s, 1H), 7.24 (d, J=2.0 Hz, 1H), 7.20-7.19 (m, 1H), 7.05-7.0 (m, 2H), 2.80-2.65 (m, 1H), 2.50 (s, 3H), 1.88-1.55 (m, 5H), 1.45-1.10 (m, 5H).

[0331] MS (ESI) C21H.sub.22BrN.sub.3O.sub.4S requires: 493, found 490 (MH).sup..

[0332] Occasionally, Boc-protected boronic acids or boronic esters were employed in the Suzuki coupling described in M3. An exemplified Boc-deprotection procedure to obtain final compound 311 is described below. A similar procedure was employed to yield compounds 342 and 343.

N-(3-amino-2-chloro-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (311)

[0333] ##STR00058##

[0334] To a stirred solution of tert-butyl (2-chloro-4-((7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline)-6-sulfonamido)-[1,1-biphenyl]-3-yl) carbamate (40 mg, 0.07 mmol) in DCM (0.50 mL) was added 4M HCl in 1, 4-dioxane (0.20 mL) at 0 C. The reaction was stirred at RT for 16 h. The mixture was concentrated in vacuo and the residue was washed with Et.sub.2O (2 mL), pentane (2 mL). The solvents were removed in vacuo to yield the desired product 311 (16 mg, 8.7%) as an off-white solid, HCl salt.

[0335] .sup.1H NMR (400 MHz, DMSO) : 12.12 (s, 1H), 11.97 (s, 1H), 10.84 (s, 1H), 7.80 (s, 1H), 7.37-7.30 (m, 1H), 7.27-7.23 (m, 2H), 7.11-7.08 (m, 1H), 7.04-6.95 (m, 4H), 2.55 (s, 3H).

[0336] MS (ESI) C21H.sub.17ClN404S requires: 456, found 455 (MH).sup..

[0337] To obtain the anilines required for the synthesis of compounds 250 and 255, 2-Bromo-4-fluoro-[1,1-biphenyl]-4-amine obtained from standard method M3 was Boc-protected, following which a Buchwald reaction was performed. Boc-deprotection yielded the required aniline.

tert-Butyl (2-bromo-4-fluoro-[1,1-biphenyl]-4-yl) carbamate (1S)

[0338] ##STR00059##

[0339] To a stirred solution of 2-bromo-4-fluoro-[1,1-biphenyl]-4-amine (1.0 g, 3.76 mmol) in THF (10 mL) at RT were added DIPEA (0.5 mL) and Boc.sub.2O (0.9 mL, 3.76 mmol). The reaction was stirred for 16 h at 80 C. The mixture was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel using a gradient of EtOAc in petroleum, followed by by prep-HPLC using a gradient of 0.1% HCOOH in H.sub.2O in MeOH to yield the desired product 1S (600 mg, 43%) as a brown solid. MS (ESI)

[0340] MS (ESI) C17H.sub.17BrFNO.sub.2 requires: 365, found 310 [MBu+H].sup.+.

tert-Butyl (4-fluoro-2-morpholino-[1,1-biphenyl]-4-yl) carbamate (1T)

[0341] ##STR00060##

[0342] To a degassed solution of intermediate 1S (200 mg, 0.546 mmol), morpholine (95 mg, 1.09 mmol) and t-BuONa (105 mg, 1.09 mmol) in toluene (5 mL) were added Pd.sub.2 (dba).sub.3 (50 mg, 0.054 mmol) and Xantphos (63 mg, 0.10 mmol) at rt. The reaction was stirred for 16 h at 100 C., upon which the mixture was cooled to rt, quenched with water and extracted with EtOAc. The combined organic layer was dried over anhydrous Na.sub.2SO.sub.4, filtered and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel, using a gradient of EtOAc in pet-ether as an eluent to afford the desired compound 1T (70 mg, 34%) as a brown solid.

[0343] MS (ESI) C21H.sub.25FN.sub.2O.sub.3 requires: 372, found 373 [M+H]+.

4-fluoro-2-morpholino-[1,1-biphenyl]-4-amine (1U)

[0344] ##STR00061##

[0345] 4N HCl in 1, 4-dioxane (0.5 mL) were added to a stirred solution of intermediate 1T (70 mg, 1.05 mmol) in DCM (3 mL) at 0 C., and the reaction was stirred for 16 h at rt. The mixture was concentrated in vacuo and the residue was washed with Et.sub.2O and dried to yield the desired product 1U (80 mg, excess weight). The crude compound was used in the following step without further purification.

[0346] MS (ESI) C16H.sub.17FN.sub.2O requires: 272, found 273 [M+H]+.

TABLE-US-00004 TABLE 1c anilines intermediates of Formula T Intermediate Formula (M + H).sup.+ 2U [00062] MS (ESI) C.sub.14H.sub.15FN.sub.2 requires: 230, found 231 [M + H].sup.+.

[0347] When the final compound contained one or more acetylene groups, silyl-group protections and deprotections were introduced to improve conversion and facilitate isolation of the intermediates. All or parts of the below-described route, leading to compound 251 were employed. It should be apparent to a person skilled in the art that the sequence of the synthetic steps, as well as reaction conditions and the protecting groups employed, are dependent on starting materials availability, functional group compatibility and operator, and could vary from compound to compound.

##STR00063##

3-((triisopropylsilyl) ethynyl) aniline (1V)

[0348] ##STR00064##

[0349] To a degassed solution of 3-iodoaniline (2.0 g, 9.13 mmol) and (triisopropylsilyl)-acetylene (1.8 g, 10.04 mmol) in DMF (10 mL) at r. t. were added Et.sub.2NH (14 mL, 137.0 mmol), Cul (70 mg, 0.365) and Pd(PPh.sub.3).sub.2Cl.sub.2 (128 mg, 0.183 mmol). The resulting reaction mixture was degassed with Ar for 15 min and stirred for 5 min at 150 C. in microwave. The reaction was allowed to cool to rt, and quenched with H.sub.2O, and extracted with Et.sub.2O. The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4, filtered and reduced in vacuo. The residue was purified by column chromatography on silica gel using a gradient of EtOAc in pet-ether to yield the desired product (1V) (1.8 g, 72%) as a brown gum.

[0350] MS (ESI) C17H.sub.27NSi requires: 273, found 274 [M+H]+.

4-Iodo-3-((triisopropylsilyl) ethynyl) aniline (1W)

[0351] ##STR00065##

[0352] NIS (2.1 g, 3.66 mmol) was added to a stirred solution of intermediate 1V (2.5 g, 9.15 mmol) in DMSO (25 mL) and the reaction was stirred at r. t. under Ar atmosphere for 4 h. The mixture was poured into cold water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using a gradient of EtOAc in pet-ether to yield the desired product 1W (1.6 g, 44%) as a brown gum.

[0353] MS (ESI) C17H.sub.26INSi requires: 399, found 400 [M+H]+.

2-((triisopropylsilyl) ethynyl)-4-((trimethylsilyl) ethynyl)-[1,1-biphenyl]-4-amine (1)

[0354] ##STR00066##

[0355] Compound 1W (300 mg, 0.88 mmol) and (4-((trimethylsilyl) ethynyl)phenyl) boronic acid (174 mg, 0.79 mmol) were dissolved in dioxane: H.sub.2O (5:1, 6 mL) and degassed Na.sub.2CO.sub.3 (188 mg, 1.76 mmol) and Pd(PPh.sub.3) 4 (31 mg, 0.02 mmol) were added at rt. The reaction was degassed with Ar for 15 min and stirred at 120 C. for 2 h in the microwave. The mixture was allowed to coolto rt, quenched with H.sub.2O, and extracted with EtOAc. The combined organic layers were dried over anhydrous Na.sub.2SO.sub.4, filtered and reduced in vacuo. The residue was purified by column chromatography on silica gel using a gradient of EtOAc in pet-ether to yield the desired product 1 (210 mg, 63%) as a pale yellow gum.

[0356] MS (ESI) C28H.sub.39NSi.sub.2 requires: 445, found 446 [M+H]+.

7-methyl-2,3-dioxo-N-(2-((triisopropylsilyl) ethynyl)-4-((trimethylsilyl) ethynyl)-[1,1-biphenyl]-4-yl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (1Y)

[0357] ##STR00067##

[0358] To a stirred solution of compound 1 (170 mg, 0.38 mmol) in pyridine (3 mL) at 0 C. was added intermediate 1A (118 mg, 0.45 mmol) and the reaction was stirred at r. t. for 2 h. The mixture was quenched with cold water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and reduced in vacuo. The crude product was purified by prep-HPLC using a gradient of NH.sub.4HCO.sub.3 in H.sub.2O in ACN to yield the desired product 1Y (15 mg, 5%) as an off-white solid.

[0359] MS (ESI) C37H.sub.45N.sub.3O.sub.4SSi.sub.2 requires: 683, not seen

N-(2,4-diethynyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide (251)

[0360] ##STR00068##

[0361] TBAF (1M in THF, 0.05 mL, 0.05 mmol) was added to a stirred solution of compound 1 (15 mg, 0.022 mmol) in THF (2 mL) at 0 C. The reaction for 2 h at rt. The mixture was quenched with cold water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and reduced in vacuo.

[0362] The residue was purified by prep-HPLC using a gradient of NH.sub.4HCO.sub.3 in H.sub.2O in ACN to yield the desired product 251 (3 mg, 33%) as an off-white solid.

[0363] MS (ESI) C25H.sub.17N.sub.3O.sub.4S requires: 455, found 454 [MH]+.

[0364] A similar deprotection step was also necessary when the boronic acid building block contained a TBS-protected phenol, as is the case for compound 386.

[0365] Further compounds exemplifying the invention are described in Table 2.

[0366] When not otherwise specified, it should be assumed that M1, M2, sometimes followed by M3 were used to yield the target compounds. This is highlighted in the Synthetic Sequence column. Occasionally, as specified in the table, a further deprotection or hydrolysis step was required to obtain the final product, as would be recognized by a person skilled in the art. It should also be apparent to a person skilled in the art that reaction conditions such as temperature, dilution, reaction time or work-up procedures, including pH adjustment, are dependent on reaction partners and functional group compatibility and could vary from compound to compound. For commercially available compounds, the CAS number is given.

TABLE-US-00005 TABLE 2 Compounds of formula (I) of the invention Synthetic .sup.1H-NMR or (M LC Structure Sequence CAS Number (M + H).sup.+ H).sup. purity 1 [00069] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.08 (s, 1H), 11.95 (s, 1H), 10.79 (s, 1H), 7.78 (s, 1H), 7.43 7.29 (m, 5H), 7.26 (dd, J = 8.4, 0.8 Hz, 1H), 7.21 (dd, J = 2.2, 0.9 Hz, 1H), 7.07 (ddd, J = 8.5, 2.3, 442 98% 0.9 Hz, 1H), 7.01 (s, 1H), 2.53 (s, 3H). 2 [00070] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.86 (s, 1H), 7.28 (d, J = 2.2 Hz, 1H), 7.23 7.07 (m, 5H), 2.64 (s, 3H). 512 100% 3 [00071] M1, M2, M3 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 11.99 (s, 1H), 10.86 (s, 1H), 7.81 (s, 1H), 7.38 (ddd, J = 8.6, 5.5, 2.6 Hz, 2H), 7.32 7.20 (m, 4H), 7.09 (dd, J = 8.4, 2.3 Hz, 1H), 7.03 (s, 1H), 460 100% 2.55 (s, 3H). 4 [00072] M1, M2, M3 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 11.98 (s, 1H), 10.80 (s, 1H), 7.81 (s, 1H), 7.34 7.15 (m, 3H), 7.13 7.00 (m, 2H), 6.79 (d, J = 8.6 Hz, 1H), 6.68 (t, J = 5.8 Hz, 2H), 2.91 (s, 6H), 2.56 (s, 3H). 485 97% 5 [00073] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.95 (s, 1H), 10.87 (s, 1H), 7.80 (s, 1H), 7.46 7.38 (m, 1H), 7.30 7.20 (m, 5H), 7.11 7.06 (m, 1H), 7.02 (s, 1H), 2.54 (s, 3H). 460 97% 6 [00074] M1, M2, M3 .sup.1H NMR (300 MHz, Methanol-d.sub.4) 7.83 (s, 1H), 7.21 (d, J = 2.2 Hz, 1H), 7.18 7.00 (m, 4H), 6.49 (dd, J = 7.9, 2.0 Hz, 2H), 6.41 (t, J = 2.0 Hz, 1H), 3.24 3.13 (m, 4H), 2.63 (s, 3H), 2.04 1.91 (m, 4H). 511 96% 7 [00075] M1, M2, M3 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 12.11 (s, 1H), 11.97 (s, 1H), 10.80 (s, 1H), 7.80 (s, 1H), 7.61 (s, 2H), 7.39 (d, J = 8.4 Hz, 1H), 7.29 7.19 (m, 2H), 7.11 6.99 (m, 2H), 2.55 (s, 3H). 448 91% 8 [00076] M1, M2, M3 .sup.1H NMR (300 MHz, Methanol-d.sub.4) 8.57 (s, 1H), 8.23 8.15 (m, 2H), 8.15 8.05 (m, 2H), 8.04 7.96 (m, 2H), 7.85 (dd, J = 8.4, 2.3 Hz, 1H), 7.79 (s, 1H), 2.78 (s, 3H). 476 98% 9 [00077] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.97 (s, 1H), 7.53 7.47 (m, 1H), 7.37 (d, J = 2.2 Hz, 1H), 7.36 7.32 (m, 2H), 7.31 (s, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.25 7.19 (m, 2H), 3.19 (s, 6H). 505 94% 10 [00078] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.18 (s, 1H), 11.97 (s, 1H), 10.95 (s, 1H), 7.62 (d, J = 6.6 Hz, 1H), 7.24 (ddd, J = 5.2, 3.1, 0.8 Hz, 2H), 7.17 (d, J = 7.8 Hz, 1H), 7.10 (ddd, J = 8.5, 2.3, 0.9 487 99% Hz, 1H), 7.00 (d, J = 10.6 Hz, 1H), 6.73 (s, 2H), 3.52 (t, J = 8.2 Hz, 2H), 3.00 (t, J = 8.2 Hz, 2H). 11 [00079] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 11.98 (s, 1H), 10.88 (s, 1H), 7.82 (s, 1H), 7.56 (dd, J = 7.2, 2.2 Hz, 1H), 7.43 (d, J = 8.6 Hz, 1H), 7.38 7.30 (m, 2H), 7.24 (d, J = 2.2 Hz, 1H), 7.07 (s, 1H), 7.03 (d, J = 0.8 Hz, 1H), 2.54 (s, 3H). 493 91% 12 [00080] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.91 (s, 1H), 7.32 7.23 (m, 4H), 7.20 7.13 (m, 2H), 7.08 7.01 (m, 2H). 480 90% 13 [00081] M1, M2, M3 .sup.1H NMR (300 MHz, Methanol-d.sub.4) 7.86 (s, 1H), 7.53 7.47 (m, 1H), 7.41 (d, J = 1.2 Hz, 1H), 7.38 (dd, J = 7.8, 1.6 Hz, 1H), 7.28 (d, J = 2.2 Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H), 7.15 7.10 483 92% (m, 1H), 7.10 (t, J = 1.2 Hz, 1H), 3.87 (t, J = 7.8 Hz, 2H), 3.36 (d, J = 7.8 Hz, 2H), 2.65 2.63 (m, 3H). 14 [00082] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.92 (s, 1H), 7.37 7.27 (m, 7H), 7.19 7.13 (m, 2H). 463 91% 15 [00083] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.97 (s, 1H), 10.76 (s, 1H), 7.81 (d, J = 0.7 Hz, 1H), 7.32 (s, 1H), 7.20 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 9.0 Hz, 2H). 478/ 480 99% 16 [00084] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.92 (s, 1H), 10.45 (s, 1H), 7.78 (d, J = 0.8 Hz, 1H), 7.67 (dt, J = 1.8, 0.9 Hz, 1H), 6.98 (s, 1H), 6.82 (s, 2H), 6.52 (ddd, J = 3.0, 1.9, 0.8 Hz, 1H), 426 97% 6.33 (dq, J = 3.3, 0.7 Hz, 1H), 2.52 (s, 3H), 1.99 (s, 6H). 17 [00085] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.92 (s, 1H), 10.42 (s, 1H), 7.77 (s, 1H), 7.37 7.26 (m, 3H), 7.25 7.19 (m, 2H), 7.05 6.97 (m, 3H), 6.93 (dd, J = 8.2, 2.4 Hz, 1H), 2.53 (s, 422 98% 3H), 2.10 (s, 3H). 18 [00086] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.17 (s, 1H), 11.97 (s, 1H), 10.99 (s, 1H), 7.62 (d, J = 6.6 Hz, 1H), 7.41 7.34 (m, 2H), 7.30 (d, J = 8.4 Hz, 1H), 7.27 7.18 (m, 3H), 7.12 (dd, J = 8.4, 2.3 Hz, 462 99% 1H), 7.00 (d, J = 10.6 Hz, 1H). 19 [00087] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.15 (s, 1H), 12.05 (s, 1H), 11.04 (s, 1H), 7.88 (s, 1H), 7.56 (dd, J = 7.2, 2.2 Hz, 1H), 7.44 (dd, J = 9.3, 8.6 Hz, 1H), 7.37 7.30 (m, 2H), 7.25 (d, J = 2.2 Hz, 1H), 7.20 (s, 1H), 7.11 (dd, J = 8.4, 2.3 Hz, 514 99% 1H). 20 [00088] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.77 (s, 1H), 7.16 7.08 (m, 5H), 3.03 (q, J = 7.5 Hz, 2H), 1.26 (t, J = 7.5 Hz, 3H). 428 96% 21 [00089] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.15 (s, 1H), 12.04 (s, 1H), 10.93 (s, 1H), 7.87 (s, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.24 7.20 (m, 2H), 7.14 (t, J = 7.9 Hz, 1H), 7.09 (dd, J = 8.4, 2.3 Hz, 1H), 529 93% 6.50 (dt, J = 8.2, 1.8 Hz, 2H), 6.40 (t, J = 2.0 Hz, 1H), 3.18 (s, 4H), 1.96 1.87 (m, 4H). 22 [00090] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.94 (s, 1H), 10.73 (s, 1H), 7.99 (t, J = 1.2 Hz, 1H), 7.76 (s, 1H), 7.71 (t, J = 1.6 Hz, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.19 (d, 432 100% J = 2.2 Hz, 1H), 7.03 (dt, J = 8.5, 1.6 Hz, 1H), 6.99 (s, 1H), 6.78 (dt, J = 1.9, 1.0 Hz, 1H), 2.52 (s, 3H). 23 [00091] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.08 (s, 1H), 11.95 (s, 1H), 10.77 (s, 1H), 7.78 (s, 1H), 7.30 7.23 (m, 2H), 7.21 (d, J = 2.2 Hz, 1H), 7.17 7.08 (m, 3H), 7.06 (ddd, J = 456 98% 8.4, 2.2, 0.6 Hz, 1H), 7.01 (s, 1H), 2.53 (s, 3H), 2.29 (s, 3H). 24 [00092] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.94 (s, 1H), 10.84 (s, 1H), 7.77 (s, 1H), 7.60 (ddd, J = 5.1, 1.2, 0.5 Hz, 1H), 7.48 (d, J = 8.5 Hz, 1H), 7.31 7.28 (m, 446 98% 1H), 7.22 (d, J = 2.3 Hz, 1H), 7.10 (ddd, J = 5.1, 3.6, 0.5 Hz, 1H), 7.06 (dd, J = 8.6, 2.3 Hz, 1H), 7.00 (s, 1H), 2.52 (s, 3H). 25 [00093] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.93 (s, 1H), 7.41 7.33 (m, 1H), 7.32 7.28 (m, 2H), 7.21 7.08 (m, 5H). 480 91% 26 [00094] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.95 (s, 1H), 10.85 (s, 1H), 7.79 (s, 1H), 7.45 7.39 (m, 2H), 7.39 7.36 (m, 1H), 7.33 7.26 (m, 2H), 7.22 (d, J = 2.2 Hz, 1H), 7.11 7.05 474 99% (m, 1H), 7.01 (s, 1H), 2.54 (s, 3H). 27 [00095] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.17 (s, 1H), 11.97 (s, 1H), 10.93 (s, 1H), 7.62 (d, J = 6.5 Hz, 1H), 7.28 (dd, J = 8.4, 0.9 Hz, 1H), 7.24 (dd, J = 2.2, 0.9 Hz, 1H), 7.18 515 96% 7.13 (m, 1H), 7.10 (ddd, J = 8.4, 2.3, 1.0 Hz, 1H), 7.01 (d, J = 10.5 Hz, 1H), 6.50 (dd, J = 8.5, 2.5 Hz, 2H), 6.40 (d, J = 2.4 Hz, 1H), 3.22 3.15 (m, 4H), 1.94 1.88 (m, 4H). 28 [00096] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.02 (s, 1H), 11.89 (s, 1H), 10.68 (s, 1H), 7.71 (s, 1H), 7.26 7.17 (m, 2H), 7.13 7.06 (m, 2H), 6.97 (d, J = 0.9 Hz, 1H), 2.49 (s, 3H). 416 99% 29 [00097] M1, M2, M3 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 12.14 (s, 1H), 12.00 (s, 1H), 10.98 (s, 1H), 8.70 8.60 (m, 2H), 8.01 (dt, J = 8.1, 1.9 Hz, 1H), 7.83 (s, 1H), 7.62 (dd, J = 8.0, 5.0 Hz, 1H), 7.40 (d, J = 8.4 Hz, 443 99% 1H), 7.28 (d, J = 2.2 Hz, 1H), 7.14 (dd, J = 8.4, 2.2 Hz, 1H), 7.04 (s, 1H), 2.54 (s, 3H). 30 [00098] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 10.97 (s, 1H), 8.43 (dd, J = 5.2, 0.7 Hz, 1H), 7.80 (s, 1H), 7.51 (dt, J = 1.5, 0.7 Hz, 1H), 7.44 7.35 (m, 2H), 7.24 (d, J = 2.2 Hz, 1H), 7.10 (dd, J = 8.5, 2.2 Hz, 1H), 7.01 (s, 1H), 2.53 (s, 477 91% 3H). 31 [00099] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.93 (d, J = 14.2 Hz, 2H), 10.67 (s, 1H), 7.72 (s, 1H), 7.29 7.21 (m, 2H), 7.17 (s, 1H), 7.14 7.08 (m, 2H), 3.77 (p, J = 6.7 Hz, 1H), 1.10 (d, J = 6.7 Hz, 6H). 442 99% 32 [00100] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 12.03 (s, 1H), 10.94 (s, 1H), 7.86 (s, 1H), 7.61 7.55 (m, 2H), 7.38 (d, J = 8.5 Hz, 1H), 7.27 7.21 (m, 2H), 7.20 (s, 1H), 468 98% 7.08 (dd, J = 8.5, 2.3 Hz, 1H). 33 [00101] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.63 (d, J = 6.4 Hz, 1H), 7.38 7.31 (m, 2H), 7.30 7.25 (m, 1H), 7.21 7.16 (m, 2H), 7.06 (q, J = 1.0 Hz, 1H), 7.04 6.98 (m, 3H), 2.13 (s, 3H). 425 95% 34 [00102] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.18 (s, 1H), 11.98 (s, 1H), 10.96 (s, 1H), 7.62 (d, J = 6.6 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.26 7.19 (m, 2H), 7.11 (dd, J = 8.4, 2.3 Hz, 1H), 7.01 (d, J = 10.7 Hz, 1H), 6.78 (dd, J = 8.4, 2.5 Hz, 1H), 6.73 6.64 (m, 488 96% 2H), 2.90 (s, 6H). 35 [00103] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.15 (s, 1H), 12.05 (s, 1H), 11.03 (s, 1H), 7.88 (s, 1H), 7.46 7.41 (m, 2H), 7.38 (q, J = 1.3 Hz, 1H), 7.34 7.28 (m, 2H), 7.25 (d, J = 2.2 Hz, 1H), 7.21 (s, 1H), 7.11 (dd, J = 8.4, 2.3 Hz, 1H). 494 100 36 [00104] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.18 (s, 1H), 11.97 (s, 1H), 11.05 (s, 1H), 7.64 (d, J = 6.6 Hz, 1H), 7.47 7.39 (m, 1H), 7.32 7.20 (m, 5H), 7.13 (dd, J = 8.4, 2.2 Hz, 1H), 7.01 (d, J = 10.6 Hz, 1H). 462 98% 37 [00105] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (s, 1H), 11.96 (s, 1H), 11.00 (s, 1H), 8.75 8.67 (m, 2H), 7.81 (s, 1H), 7.64 7.56 (m, 2H), 7.40 (d, J = 8.5 Hz, 1H), 7.26 (d, J = 2.2 Hz, 1H), 7.14 (dd, 443 99% J = 8.5, 2.2 Hz, 1H), 7.02 (s, 1H), 2.52 (s, 3H). 38 [00106] M1, M2, M3 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 11.99 (s, 1H), 10.82 (s, 1H), 7.80 (s, 1H), 7.23 (d, J = 8.2 Hz, 6H), 7.12 6.97 (m, 2H), 2.55 (s, 3H), 2.32 (s, 3H). 456 97% 39 [00107] M1, M2, M3 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 11.99 (s, 1H), 10.83 (s, 1H), 7.81 (s, 1H), 7.37 7.26 (m, 2H), 7.24 (d, J = 2.0 Hz, 2H), 7.19 (s, 1H), 7.17 7.12 (m, 1H), 7.09 (dd, J = 8.4, 2.1 484 92% Hz, 1H), 7.04 (s, 1H), 2.95 2.83 (m, 1H), 2.56 (s, 3H), 1.19 (d, J = 6.9 Hz, 6H). 40 [00108] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.17 (s, 1H), 11.97 (s, 1H), 10.98 (s, 1H), 7.63 (d, J = 6.6 Hz, 1H), 7.43 7.38 (m, 2H), 7.37 7.31 (m, 3H), 7.30 (d, J = 8.3 Hz, 1H), 7.26 (d, J = 2.2 Hz, 1H), 445 99% 7.15 7.10 (m, 1H), 7.01 (d, J = 10.7 Hz, 1H). 41 [00109] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.99 (br. s, 1H), 10.40 (br. s, 1H) 7.80 (s, 1H), 7.34 (s, 1H), 7.01 (d, J = 8.6 Hz, 2H), 6.99 6.93 (m, 2H), 2.44 2.35 (m, 2H), 1.52 440 99% 1.39 (m, 2H), 0.80 (t, J = 7.3 Hz, 3H). 42 [00110] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.92 (s, 1H), 10.31 (s, 1H), 7.77 (s, 1H), 7.56 (ddd, J = 4.9, 2.9, 0.7 Hz, 1H), 7.20 (ddd, J = 3.0, 1.3, 0.7 Hz, 1H), 6.98 (s, 442 98% 1H), 6.87 (ddd, J = 4.9, 1.3, 0.7 Hz, 1H), 6.79 (d, J = 0.8 Hz, 2H), 2.52 (s, 3H), 1.89 (s, 6H). 43 [00111] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.14 (s, 1H), 12.05 (s, 1H), 11.05 (s, 1H), 7.44 7.41 (m, 2H), 7.38 (q, J = 1.4 Hz, 1H), 7.35 7.27 (m, 2H), 7.23 (d, J = 2.2 Hz, 1H), 7.10 (dd, J = 8.4, 2.3 Hz, 494 94% 1H), 6.81 (s, 1H), 2.56 (s, 3H). 44 [00112] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 12.03 (s, 1H), 10.91 (s, 1H), 8.00 (t, J = 1.2 Hz, 1H), 7.85 (s, 1H), 7.71 (t, J = 1.7 Hz, 1H), 7.45 (d, J = 8.5 Hz, 1H), 7.22 (d, 452 98% J = 2.3 Hz, 1H), 7.19 (s, 1H), 7.07 (dd, J = 8.5, 2.3 Hz, 1H), 6.79 (dd, J = 1.9, 0.9 Hz, 1H). 45 [00113] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 12.02 (s, 1H), 10.60 (s, 1H), 7.86 (s, 1H), 7.41 7.33 (m, 2H), 7.32 7.26 (m, 1H), 7.25 7.17 (m, 3H), 7.07 7.00 (m, 2H), 7.00 6.94 (m, 440 95% 1H), 2.11 (s, 3H). 46 [00114] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.15 (s, 1H), 12.04 (s, 1H), 10.94 (s, 1H), 7.87 (s, 1H), 7.25 7.20 (m, 3H), 7.16 (d, J = 7.6 Hz, 1H), 7.08 (dd, J = 8.5, 2.2 Hz, 1H), 6.72 (s, 2H), 3.55 3.47 503 91% (m, 2H), 2.99 (t, J = 8.2 Hz, 2H). 47 [00115] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.84 (s, 1H), 7.26 (s, 1H), 7.23 7.20 (m, 2H), 7.12 (dtt, J = 6.8, 1.9, 1.0 Hz, 2H). 436 95% 48 [00116] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.18 (s, 1H), 12.08 (s, 1H), 11.12 (s, 1H), 8.64 (dd, J = 4.7, 1.8 Hz, 2H), 7.96 (dt, J = 8.1, 2.0 Hz, 1H), 7.92 (s, 1H), 7.58 (dd, J = 8.0, 4.9 Hz, 1H), 7.42 (d, 463 99% J = 8.4 Hz, 1H), 7.32 (d, J = 2.2 Hz, 1H), 7.24 (s, 1H), 7.18 (dd, J = 8.4, 2.2 Hz, 1H). 49 [00117] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.51 (br. s, 1H), 7.70 (s, 1H), 7.04 6.99 (m, 2H), 6.99 6.91 (m, 3H), 2.52 (s, 3H), 2.41 (dd, J = 8.5, 6.7 Hz, 2H), 1.54 1.42 (m, 374 97% 2H), 0.82 (t, J = 7.3 Hz, 3H). 50 [00118] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.92 (s, 1H), 10.98 (s, 1H), 7.77 (s, 1H), 7.58 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 6.98 (s, 1H), 2.50 (d, J = 0.9 Hz, 3H). 440 96% 51 [00119] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.82 (s, 1H), 7.35 (tdd, J = 7.5, 5.2, 1.8 Hz, 1H), 7.24 6.99 (m, 4H), 6.85 (s, 2H), 2.63 (s, 3H), 1.89 (s, 6H). 454 98% 52 [00120] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.82 (s, 1H), 7.34 (d, J = 8.5 Hz, 1H), 7.22 (d, J = 2.3 Hz, 1H), 7.07 (s, 1H), 7.04 7.00 (m, 2H), 6.71 (d, J = 3.1 Hz, 1H), 2.62 (s, 3H), 462 98% 2.46 (d, J = 1.0 Hz, 3H). 53 [00121] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.03 (s, 1H), 11.88 (s, 1H), 10.16 (s, 1H), 7.66 (s, 1H), 7.03 6.81 (m, 5H), 1.75 (td, J = 8.4, 4.3 Hz, 1H), 0.88 0.75 (m, 2H), 0.57 372 100% 0.47 (m, 2H). 54 [00122] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.18 11.67 (br. m, 2H), 10.12 (br. s, 1H), 7.68 (s, 1H), 6.95 (d, J = 0.9 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.78 6.70 (m, 2H), 2.54 (d, 386 98% J = 5.4 Hz, 4H), 2.49 (s, 3H), 1.62 (dq, J = 6.6, 2.8 Hz, 4H). 55 [00123] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 11.80 (br. m, 2H), 10.34 (br. s, 1H), 7.76 (s, 1H), 7.16 (s, 1H), 7.06 6.93 (m, 4H), 2.39 (dd, J = 8.5, 6.7 Hz, 2H), 1.54 1.39 392 100% (m, 2H), 0.80 (t, J = 7.3 Hz, 3H). 56 [00124] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (s, 1H), 11.96 (s, 1H), 11.29 (br. s, 1H), 7.80 (s, 1H), 7.71 (d, J = 8.7 Hz, 1H), 7.28 (s, 1H), 7.13 (d, J = 8.8 Hz, 1H), 7.02 (s, 1H), 2.53 434 96% (s, 3H). 57 [00125] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.94 (s, 1H), 10.38 (s, 1H), 7.79 (s, 1H), 7.45 7.34 (m, 2H), 7.11 (t, J = 1.9 Hz, 1H), 7.04 6.97 (m, 2H), 6.82 (s, 2H), 2.53 (s, 3H), 1.84 (s, 470 94% 6H). 58 [00126] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.82 (s, 1H), 7.42 (dd, J = 5.2, 1.2 Hz, 1H), 7.08 7.05 (m, 2H), 6.84 (p, J = 0.6 Hz, 2H), 6.72 (dd, J = 3.5, 1.2 Hz, 1H), 2.63 (s, 3H), 442 97% 1.99 (s, 6H). 59 [00127] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d6) 12.25 11.73 (br. m, 2H), 10.29 (br. s, 1H), 7.78 (d, J = 0.9 Hz, 1H), 7.22 7.12 (m, 1H), 479 94% 6.99 (s, 1H), 6.78 (s, 2H), 6.65 6.60 (m, 1H), 6.32 6.24 (m, 2H), 2.83 (s, 6H), 2.54 (s, 3H), 1.86 (s, 6H). 60 [00128] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.81 (s, 1H), 7.75 7.61 (m, 3H), 7.51 (d, J = 2.2 Hz, 1H), 7.39 (ddd, J = 8.3, 6.9, 1.4 Hz, 1H), 7.33 (ddd, J = 8.2, 6.9, 1.3 Hz, 1H), 382 99% 7.24 (dd, J = 8.8, 2.2 Hz, 1H), 7.02 (s, 1H), 2.63 (s, 3H). 61 [00129] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.21 11.61 (br. m, 2H), 10.56 (br. s, 1H), 7.76 (s, 1H), 7.59 7.45 (m, 4H), 7.38 (t, J = 7.7 Hz, 2H), 7.32 7.23 (m, 1H), 7.16 7.05 (m, 2H), 6.97 (s, 408 97% 1H), 2.52 (s, 3H). 62 [00130] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.94 (s, 1H), 10.86 (s, 1H), 7.78 (s, 1H), 7.47 (d, J = 5.1 Hz, 1H), 7.31 7.20 (m, 2H), 7.08 7.00 (m, 2H), 6.93 (d, J = 5.1 Hz, 1H), 2.53 (s, 462 98% 3H), 1.95 (s, 3H). 63 [00131] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.51 (d, J = 8.7 Hz, 1H), 7.31 (d, J = 2.5 Hz, 1H), 6.98 (dd, J = 8.7, 2.6 Hz, 1H), 6.85 6.83 (m, 1H), 2.60 (s, 3H). 462 82% 64 [00132] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 11.95 (s, 1H), 10.69 (s, 1H), 7.59 (d, J = 6.6 Hz, 1H), 7.58 7.52 (m, 4H), 7.39 (t, J = 7.7 Hz, 2H), 7.29 (t, J = 7.3 Hz, 1H), 7.19 7.15 (m, 2H), 410 99% 6.97 (d, J = 10.6 Hz, 1H). 65 [00133] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.18 (s, 1H), 11.98 (s, 1H), 11.04 (s, 1H), 7.63 (d, J = 6.5 Hz, 1H), 7.41 7.37 (m, 1H), 7.27 (d, J = 2.2 Hz, 1H), 7.13 (ddd, J = 8.5, 2.3, 0.8 Hz, 1H), 7.01 (d, J = 478 99% 10.6 Hz, 1H). 66 [00134] M1, M2, M3 .sup.1H NMR (300 MHz, Methanol-d.sub.4) 9.02 (s, 1H), 8.71 (s, 2H), 7.79 (s, 1H), 7.25 (dd, J = 5.3, 3.1 Hz, 2H), 7.09 (dd, J = 8.4, 2.2 Hz, 1H), 6.99 (s, 1H), 2.55 (s, 3H). 442 97% 67 [00135] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.71 (s, 1H), 7.11 (s, 1H), 6.96 6.86 (m, 4H), 3.01 (q, J = 7.5 Hz, 2H), 1.78 (tt, J = 8.4, 5.1 Hz, 1H), 1.26 (t, J = 7.5 Hz, 3H), 0.92 384 91% 0.81 (m, 2H), 0.61 0.48 (m, 2H). 68 [00136] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.15 11.68 (br. m, 2H), 10.29 (br. s, 1H), 7.45 (d, J = 6.5 Hz, 1H), 6.92 6.85 (m, 5H), 1.73 (tt, J = 8.3, 5.1 Hz, 1H), 0.83 0.75 376 90% (m, 2H), 0.53 0.44 (m, 2H). 69 [00137] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.92 (s, 1H), 10.75 (s, 1H), 7.75 (s, 1H), 7.61 (d, J = 8.7 Hz, 1H), 7.17 (d, J = 2.3 Hz, 1H), 7.07 (dd, J = 8.7, 2.3 Hz, 1H), 446 97% 6.99 (s, 1H), 6.83 (d, J = 3.3 Hz, 1H), 6.19 (dd, J = 3.4, 1.2 Hz, 1H), 2.51 (s, 3H), 2.28 (s, 3H). 70 [00138] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.92 (s, 1H), 10.41 (s, 1H), 7.78 (s, 1H), 6.99 (s, 1H), 6.81 (s, 2H), 6.76 (dt, J = 3.3, 1.2 Hz, 1H), 6.59 6.49 (m, 1H), 2.52 454 94% (s, 3H), 2.42 (s, 3H), 1.96 (s, 6H). 71 [00139] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (br. s, 1H), 11.92 (br. s, 1H), 10.41 (br. s, 1H), 7.53 (d, J = 6.6 Hz, 1H), 7.10 7.03 (m, 2H), 7.01 6.93 (m, 3H), 2.41 2.25 (m, 1H), 1.78 1.61 416 97% (m, 5H), 1.34 1.10 (m, 5H). 72 [00140] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.95 (s, 1H), 10.74 (s, 1H), 7.80 (s, 1H), 7.37 7.29 (m, 1H), 7.20 7.11 (m, 2H), 7.07 7.00 (m, 4H), 6.98 6.90 (m, 1H), 3.65 (s, 3H), 2.54 472 98% (s, 3H). 73 [00141] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.93 (s, 1H), 10.32 (s, 1H), 7.79 (s, 1H), 7.38 (tt, J = 6.8, 0.9 Hz, 2H), 7.33 7.25 (m, 1H), 7.06 6.96 (m, 3H), 6.81 (s, 2H), 2.53 (s, 3H), 1.83 436 100% (s, 6H). 74 [00142] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.16 (s, 1H), 11.95 (s, 1H), 10.52 (s, 1H), 7.61 (d, J = 6.5 Hz, 1H), 7.39 (t, J = 7.5 Hz, 2H), 7.30 (dd, J = 8.4, 6.3 Hz, 1H), 7.07 6.97 (m, 3H), 6.85 (s, 2H), 438 99% 75 [00143] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.90 (s, 1H), 10.80 (s, 1H), 7.70 (s, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.23 (d, J = 2.5 Hz, 1H), 6.97 (s, 1H), 6.91 (dd, J = 8.8, 446 100% 2.6 Hz, 1H), 2.48 (s, 3H). 76 [00144] commercial 894919-20-1 77 [00145] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (s, 1H), 11.96 (s, 1H), 10.83 (s, 1H), 7.80 (s, 1H), 7.55 7.47 (m, 1H), 7.37 (pd, J = 7.4, 1.8 Hz, 2H), 7.27 7.17 (m, 3H), 7.10 7.00 (m, 2H), 2.54 (s, 476 99% 3H). 78 [00146] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.95 (s, 1H), 10.77 (s, 1H), 7.79 (s, 1H), 7.54 7.49 (m, 1H), 7.36 (td, J = 7.5, 1.5 Hz, 1H), 7.24 (td, J = 7.6, 1.4 Hz, 1H), 7.19 (d, J = 2.2 Hz, 469 94% 1H), 7.15 (d, J = 8.3 Hz, 1H), 7.06 6.96 (m, 3H), 4.21 4.03 (m, 2H), 2.53 (s, 3H). 79 [00147] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.02 (s, 1H), 11.88 (s, 1H), 10.13 (s, 1H), 7.67 (s, 1H), 7.01 (d, J = 8.1 Hz, 1H), 6.95 (d, J = 0.9 Hz, 1H), 6.91 (d, J = 2.0 Hz, 1H), 6.79 372 98% (dd, J = 8.0, 2.1 Hz, 1H), 2.70 (q, J = 7.8 Hz, 4H), 2.49 (s, 3H), 1.91 (p, J = 7.4 Hz, 2H). 80 [00148] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 12.01 (s, 1H), 10.49 (s, 1H), 7.85 (s, 1H), 7.58 (ddd, J = 5.0, 2.9, 0.8 Hz, 1H), 7.22 (dt, J = 2.9, 1.0 Hz, 1H), 7.19 (s, 1H), 460 99% 6.88 (dt, J = 4.9, 1.0 Hz, 1H), 6.83 (s, 2H), 1.90 (s, 6H). 81 [00149] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.96 (s, 1H), 10.54 (s, 1H), 7.82 (s, 1H), 7.38 7.27 (m, 4H), 7.27 7.19 (m, 1H), 7.10 (dd, J = 8.2, 0.8 Hz, 1H), 6.99 (s, 1H), 6.82 (d, J = 2.1 438 98% Hz, 1H), 6.71 6.63 (m, 1H), 3.64 (s, 3H), 2.54 (s, 3H). 82 [00150] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.66 (d, J = 6.4 Hz, 1H), 7.45 7.39 (m, 2H), 7.33 7.28 (m, 2H), 7.21 (dd, J = 4.9, 1.4 Hz, 1H), 7.11 (dd, J = 8.4, 2.3 Hz, 1H), 7.01 450 96% (d, J = 10.4 Hz, 1H). 83 [00151] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.89 (s, 1H), 10.24 (s, 1H), 7.71 (s, 1H), 7.26 7.14 (m, 2H), 7.01 6.89 (m, 3H), 2.48 (s, 3H), 1.16 (s, 9H). 388 99% 84 [00152] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.92 (s, 1H), 10.42 (s, 1H), 7.77 (s, 1H), 6.98 (s, 1H), 6.80 (s, 2H), 6.17 (dd, J = 3.1, 0.7 Hz, 1H), 6.10 (dq, J = 3.0, 0.8 Hz, 1H), 2.52 (s, 3H), 2.23 440 98% (s, 3H), 2.02 (s, 6H). 85 [00153] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.77 (s, 1H), 7.24 (s, 1H), 7.03 6.98 (m, 2H), 6.91 6.86 (m, 2H), 1.76 (tt, J = 8.4, 5.1 Hz, 1H), 0.90 0.81 (m, 2H), 0.57 0.49 390 97% (m, 2H). 86 [00154] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.89 (s, 1H), 10.21 (s, 1H), 7.70 (s, 1H), 7.07 7.00 (m, 2H), 6.98 6.90 (m, 3H), 2.49 (d, J = 0.7 Hz, 3H), 2.34 (s, 1H), 1.75 1.57 (m, 5H), 414 98% 1.37 1.07 (m, 5H). 87 [00155] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.45 (d, J = 6.4 Hz, 1H), 7.00 6.85 (m, 5H), 2.41 2.32 (m, 2H), 1.50 1.38 (m, 2H), 0.76 (t, J = 7.3 Hz, 3H). 376 90% 88 [00156] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (br. s, 1H), 12.00 (br. s, 1H), 10.54 (s, 1H), 7.82 (s, 1H), 7.76 (t, J = 1.1 Hz, 1H), 7.67 (t, J = 1.7 Hz, 1H), 7.23 7.16 (m, 2H), 6.99 (d, J = 2.3 Hz, 1H), 6.93 430 95% (dd, J = 8.3, 2.4 Hz, 1H), 6.67 (dd, J = 1.9, 0.9 Hz, 1H), 2.23 (s, 3H). 89 [00157] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.91 (s, 1H), 10.45 (s, 1H), 7.75 (s, 1H), 7.25 7.13 (m, 5H), 7.10 7.05 (m, 3H), 6.99 (s, 1H), 2.51 (d, J = 0.8 Hz, 3H), 2.12 (s, 3H). 422 95% 90 [00158] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.83 (s, 1H), 7.26 7.18 (m, 3H), 7.18 7.12 (m, 1H), 7.09 (d, J = 0.9 Hz, 1H), 7.07 7.02 (m, 2H), 6.97 (dd, J = 7.4, 1.2 Hz, 1H), 2.64 (d, J = 0.7 456 96% Hz, 3H), 1.97 (s, 3H). 91 [00159] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.92 (s, 1H), 10.90 (s, 1H), 7.78 (s, 1H), 7.49 (d, J = 8.6 Hz, 1H), 7.04 (s, 1H), 7.01 6.97 (m, 2H), 2.50 (s, 3H), 2.32 412 99% 2.29 (m, 3H). 92 [00160] commercial 894915-45-8 93 [00161] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.92 (s, 1H), 7.53 7.46 (m, 2H), 7.32 7.26 (m, 2H), 7.24 (s, 1H). 420 97% 94 [00162] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 8.86 8.78 (m, 2H), 8.04 7.97 (m, 3H), 7.51 7.42 (m, 2H), 7.35 7.28 (m, 2H). 463 96% 95 [00163] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.90 (s, 1H), 10.79 (s, 1H), 7.79 (dd, J = 8.6, 5.0 Hz, 2H), 7.73 (d, J = 8.2 Hz, 1H), 7.60 (d, J = 6.6 Hz, 1H), 7.54 (d, 384 98% J = 2.1 Hz, 1H), 7.47 7.34 (m, 2H), 7.30 (dd, J = 8.8, 2.2 Hz, 1H), 6.93 (d, J = 10.6 Hz, 1H). 96 [00164] M1, M2 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 12.03 (s, 1H), 10.41 (s, 1H), 7.82 (s, 1H), 7.36 (s, 1H), 7.00 6.89 (m, 4H), 1.78 (tt, J = 8.4, 5.1 Hz, 1H), 0.90 0.81 (m, 2H), 0.59 0.50 (m, 2H). 436 95% 97 [00165] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.89 (s, 1H), 10.54 (s, 1H), 7.69 (s, 1H), 7.44 7.37 (m, 2H), 7.01 6.96 (m, 3H), 2.50 (s, 3H). 410 98% 98 [00166] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.16 11.93 (br. m, 2H), 10.67 (br. s, 1H), 7.84 (s, 1H), 7.58 7.48 (m, 4H), 7.38 (dd, J = 8.3, 6.9 Hz, 2H), 7.33 7.24 (m, 1H), 7.20 7.12 (m, 3H). 426 99% 99 [00167] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.18 (s, 1H), 11.98 (s, 1H), 11.09 (s, 1H), 8.62 8.57 (m, 2H), 7.91 7.84 (m, 1H), 7.64 (d, J = 6.6 Hz, 1H), 7.55 7.48 (m, 1H), 7.39 (d, J = 8.5 Hz, 1H), 7.30 445 99% (d, J = 2.3 Hz, 1H), 7.17 (dd, J = 8.4, 2.2 Hz, 1H), 7.01 (d, J = 10.5 Hz, 1H). 100 [00168] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.96 11.93 (m, 2H), 10.82 (s, 1H), 7.76 (s, 1H), 7.59 (dd, J = 3.0, 1.4 Hz, 1H), 7.56 (dd, J = 4.9, 3.0 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.23 (dd, J = 5.0, 1.4 474 99% Hz, 1H), 7.20 7.17 (m, 2H), 7.03 (dd, J = 8.5, 2.3 Hz, 1H), 3.80 (p, J = 6.7 Hz, 1H), 1.13 (d, J = 6.7 Hz, 6H). 101 [00169] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (br. s, 1H), 11.92 (br. s, 1H), 10.41 (br. s, 1H), 7.53 (d, J = 6.5 Hz, 1H), 7.09 (d, J = 8.4 Hz, 2H), 7.03 6.92 (m, 3H), 2.75 (p, 376 99% J = 7.0 Hz, 1H), 1.09 (d, J = 6.9 Hz, 6H). 102 [00170] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (br. s, 1H), 11.93 (br. s, 1H), 10.28 (br. s, 1H), 7.79 (s, 1H), 7.29 (ddd, J = 8.7, 7.3, 1.8 Hz, 1H), 7.06 6.98 (m, 2H), 6.94 (td, J = 7.3, 1.0 Hz, 1H), 6.86 466 97% (dd, J = 7.4, 1.8 Hz, 1H), 6.77 (d, J = 0.9 Hz, 2H), 3.61 (s, 3H), 2.53 (s, 3H), 1.77 (s, 6H). 103 [00171] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.93 (s, 1H), 10.35 (s, 1H), 7.76 (s, 1H), 7.26 7.13 (m, 3H), 7.02 6.92 (m, 3H), 6.91 6.85 (m, 2H), 2.55 2.50 (m, 3H), 1.90 1.84 436 98% (m, 6H). 104 [00172] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.91 (s, 1H), 10.35 (s, 1H), 7.79 (s, 1H), 7.56 7.50 (m, 1H), 7.40 7.33 (m, 2H), 7.14 7.08 (m, 1H), 7.00 (s, 1H), 6.81 (s, 2H), 2.53 (s, 3H), 470 95% 1.78 (s, 6H). 105 [00173] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.94 (s, 1H), 7.33 (dd, J = 1.9, 0.7 Hz, 1H), 7.28 (s, 1H), 7.23 7.17 (m, 3H), 7.15 (dd, J = 8.6, 1.5 Hz, 1H). 530 93% 106 [00174] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.88 (s, 1H), 7.39 7.31 (m, 2H), 7.28 (d, J = 7.3 Hz, 2H), 7.01 6.95 (m, 2H), 6.93 6.87 (m, 2H), 1.86 (s, 6H). 454 92% 107 [00175] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.92 (s, 1H), 10.30 (s, 1H), 7.76 (s, 1H), 7.73 7.67 (m, 1H), 7.51 (dt, J = 1.4, 0.7 Hz, 1H), 6.97 (s, 1H), 6.79 (d, J = 0.8 426 98% Hz, 2H), 6.36 (dt, J = 1.6, 0.7 Hz, 1H), 2.52 (s, 3H), 1.97 (s, 6H). 108 [00176] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.92 (br. s, 2H), 10.66 (br. s, 1H), 7.78 (s, 1H), 7.50 7.47 (m, 1H), 7.37 7.23 (m, 5H), 7.11 7.06 (m, 2H), 6.99 (s, 1H), 2.53 (s, 3H). 442 97% 109 [00177] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.96 (br. s, 2H), 11.95 (br. s, 1H), 10.80 (s, 1H), 7.77 (s, 1H), 7.25 (d, J = 8.4 Hz, 1H), 7.22 7.16 (m, 3H), 7.04 (dd, J = 8.4, 2.2 Hz, 1H), 6.73 (d, J = 8.4 511 97% Hz, 1H), 6.61 (d, J = 9.4 Hz, 2H), 3.81 (p, J = 6.7 Hz, 2H), 2.85 (s, 6H), 1.14 (d, J = 6.7 Hz, 6H). 110 [00178] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.86 (br. s, 2H), 9.46 (br. s, 1H), 7.47 (s, 1H), 7.00 (d, J = 0.8 Hz, 1H), 6.82 (d, J = 1.8 Hz, 1H), 6.77 6.69 (m, 2H), 2.46 (s, 3H), 2.00 386 98% (s, 3H), 1.77 (tt, J = 8.4, 5.1 Hz, 1H), 0.93 0.79 (m, 2H), 0.63 0.50 (m, 2H). 111 [00179] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.87 (s, 1H), 9.92 (s, 1H), 7.59 (s, 1H), 6.96 (s, 1H), 6.95 6.89 (m, 2H), 6.79 6.71 (m, 2H), 3.88 (q, J = 7.0 376 100% Hz, 2H), 2.47 (s, 3H), 1.27 1.20 (m, 3H). 112 [00180] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.82 (br. s, 2H), 10.54 (br. s, 1H), 7.75 (s, 1H), 7.35 7.19 (m, 5H), 7.04 6.86 (m, 4H), 2.51 (s, 3H), 2.29 (s, 3H). 420 98% 113 [00181] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.92 (br. s, 2H), 10.48 (br. s, 1H), 7.75 (s, 1H), 7.26 7.21 (m, 2H), 7.19 7.10 (m, 3H), 7.09 7.01 (m, 3H), 6.98 (s, 1H), 2.52 (s, 3H), 2.42 (q, J = 7.5 436 91% Hz, 2H), 0.93 (t, J = 7.5 Hz, 3H). 114 [00182] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.91 (br. s, 1H), 10.47 (br. s, 1H), 7.77 (s, 1H), 7.32 7.22 (m, 3H), 7.17 (dd, J = 7.6, 1.8 Hz, 1H), 7.07 7.00 (m, 3H), 7.00 6.92 (m, 2H), 3.69 (d, J = 438 98% 0.6 Hz, 3H), 2.53 (s, 3H). 115 [00183] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.91 (s, 1H), 10.46 (s, 1H), 7.75 (s, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.18 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 8.3 Hz, 2H), 422 91% 6.97 (s, 1H), 2.52 (s, 3H), 2.28 (s, 3H). 116 [00184] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.92 (s, 1H), 10.34 (s, 1H), 7.71 (s, 1H), 7.11 7.01 (m, 5H), 7.00 6.93 (m, 3H), 2.50 (s, 3H), 1.84 (s, 6H). 434 98% 117 [00185] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.90 (s, 1H), 10.15 (s, 1H), 7.71 (s, 1H), 7.05 7.01 (m, 1H), 6.97 (d, J = 0.8 Hz, 1H), 6.82 (d, J = 7.6 Hz, 2H), 2.94 (p, J = 388 100% 6.9 Hz, 1H), 2.50 (s, 3H), 2.15 (s, 3H), 1.06 (d, J = 6.8 Hz, 6H). 118 [00186] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.73 (s, 1H), 7.09 7.01 (m, 4H), 6.99 (d, J = 0.8 Hz, 1H), 6.96 (s, 1H), 6.91 (t, J = 1.0 Hz, 2H), 2.51 (s, 3H), 2.21 (s, 3H), 2.04 (s, 3H). 434 95% 119 [00187] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.91 (s, 1H), 10.39 (s, 1H), 7.74 (s, 1H), 7.34 (d, J = 8.3 Hz, 2H), 7.22 (s, 1H), 7.15 6.90 (m, 6H), 2.52 (s, 6H), 2.40 (s, 3H). 451 98% 120 [00188] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.92 (s, 1H), 10.49 (s, 1H), 7.76 (s, 1H), 7.63 (dd, J = 7.6, 1.4 Hz, 1H), 7.53 (td, J = 7.5, 1.3 Hz, 1H), 7.40 (tt, J = 7.5, 0.9 Hz, 1H), 7.33 7.27 (m, 1H), 7.14 7.04 (m, 4H), 6.97 (s, 1H), 480 98% 3.94 3.80 (m, 2H), 2.52 (s, 3H), 0.72 (td, J = 7.1, 0.6 Hz, 3H). 121 [00189] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.93 (s, 1H), 10.58 (s, 1H), 7.76 (s, 1H), 7.36 (dd, J = 8.5, 0.6 Hz, 1H), 6.97 (s, 1H), 6.80 (d, J = 2.4 Hz, 1H), 6.58 6.48 (m, 1H), 3.73 (s, 3H), 440 100% 2.50 (s, 3H). 122 [00190] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.03 (s, 1H), 11.89 (s, 1H), 10.40 (s, 1H), 7.71 (s, 1H), 6.96 (s, 1H), 6.85 (s, 2H), 2.49 (s, 3H), 2.21 (s, 6H). 438 100% 123 [00191] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.91 (s, 1H), 10.50 (s, 1H), 7.73 (s, 1H), 7.53 7.24 (m, 4H), 7.15 7.05 (m, 4H), 6.97 (s, 1H), 2.51 (s, 3H), 1.96 (s, 3H). 450 100% 124 [00192] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.96 (s, 1H), 10.47 (s, 1H), 7.80 (s, 1H), 7.20 7.14 (m, 2H), 7.14 7.08 (m, 1H), 6.99 (s, 1H), 6.95 (dt, J = 7.2, 1.1 Hz, 1H), 6.88 (d, J = 8.1 452 100% Hz, 1H), 6.78 (d, J = 2.0 Hz, 1H), 6.63 (dd, J = 8.1, 2.0 Hz, 1H), 3.58 (s, 3H), 2.53 (d, J = 0.7 Hz, 3H), 1.92 (s, 3H). 125 [00193] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.92 (br. s, 2H), 10.23 (br. s, 1H), 7.76 (s, 1H), 7.30 7.14 (m, 3H), 6.99 (s, 1H), 6.90 6.82 (m, 1H), 6.80 (s, 2H), 2.52 (s, 3H), 1.78 (s, 3H), 1.73 (s, 6H). 450 100% 126 [00194] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.90 (br. s, 2H), 10.48 (br. s, 1H), 7.76 (s, 1H), 7.53 (d, J = 2.1 Hz, 1H), 7.41 7.26 (m, 3H), 7.26 7.14 (m, 4H), 7.06 6.93 (m, 3H), 2.50 (s, 3H). 451 98% 127 [00195] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.92 (s, 1H), 10.76 (s, 1H), 8.57 8.49 (m, 2H), 7.78 (s, 1H), 7.67 (d, J = 8.5 Hz, 2H), 7.60 7.55 (m, 2H), 7.20 7.10 (m, 2H), 6.97 (s, 1H), 409 90% 2.52 (s, 3H). 128 [00196] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.92 (s, 1H), 10.39 (s, 1H), 7.69 (s, 1H), 7.28 (d, J = 2.2 Hz, 1H), 7.06 6.96 (m, 3H), 3.71 3.60 (m, 4H), 2.88 2.73 (m, 4H), 2.49 (s, 3H). 495/ 497 97% 129 [00197] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.92 (s, 1H), 11.14 (s, 1H), 7.78 (s, 1H), 7.71 7.61 (m, 2H), 7.20 7.11 (m, 2H), 6.98 (s, 1H), 2.49 (s, 3H). 357 100% 130 [00198] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.90 (br. s, 2H), 10.65 (br. s, 1H), 7.73 (s, 1H), 7.34 7.28 (m, 2H), 7.05 6.99 (m, 2H), 6.96 (d, J = 0.8 Hz, 1H), 2.49 (s, 3H). 356 97% 131 [00199] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.08 (s, 1H), 11.95 (s, 1H), 10.51 (s, 1H), 8.75 (d, J = 5.9 Hz, 2H), 7.81 (d, J = 1.1 Hz, 1H), 7.48 (d, J = 5.9 Hz, 2H), 7.00 (d, J = 1.0 Hz, 1H), 6.89 6.84 437 100% (m, 2H), 2.54 (d, J = 0.9 Hz, 3H), 1.87 (d, J = 1.1 Hz, 6H). 132 [00200] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.93 (s, 1H), 10.40 (s, 1H), 7.78 (s, 1H), 7.44 (d, J = 5.1 Hz, 1H), 6.99 (d, J = 0.9 Hz, 1H), 6.96 (d, J = 5.1 Hz, 1H), 6.82 (s, 2H), 2.52 (s, 3H), 1.87 (s, 6H), 1.78 (s, 3H). 456 100% 133 [00201] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.87 (s, 1H), 9.81 (s, 1H), 7.59 (s, 1H), 6.97 (s, 1H), 6.87 (d, J = 8.5 Hz, 2H), 6.68 (s, 2H), 2.82 (s, 6H), 2.49 (s, 375 100% 3H). 134 [00202] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (br. s, 1H), 11.94 (br. s, 1H), 10.23 (br. s, 1H), 7.75 (s, 1H), 7.32 7.15 (m, 3H), 6.98 (d, J = 0.8 Hz, 1H), 6.87 6.77 (m, 3H), 2.51 (s, 3H), 2.07 (q, J = 7.5 Hz, 2H), 1.74 (s, 6H), 0.91 0.82 (m, 3H). 464 100% 135 [00203] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.91 (s, 1H), 10.74 (s, 1H), 10.15 (s, 1H), 7.75 (s, 1H), 6.98 (s, 1H), 6.81 6.71 (m, 3H), 6.51 (dq, J = 2.9, 1.4 Hz, 425 100% 1H), 5.81 (dp, J = 2.6, 1.2 Hz, 1H), 2.52 (s, 3H), 1.95 (s, 6H). 136 [00204] M1, M2, M3 .sup.1H NMR (300 MHz, Methanol-d.sub.4) 7.93 (s, 1H), 7.77 (d, J = 8.2 Hz, 1H), 7.63 (dd, J = 8.6, 7.1 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 7.37 (d, J = 2.2 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.20 (ddd, J = 485 94% 8.4, 4.4, 1.9 Hz, 2H), 7.11 (s, 1H), 3.08 (s, 6H), 2.67 (s, 3H). 137 [00205] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.03 (s, 1H), 11.85 (s, 1H), 9.56 (s, 1H), 7.53 (s, 1H), 6.97 (s, 1H), 6.84 6.76 (m, 2H), 6.36 (d, J = 8.5 Hz, 2 H), 3.14 3.04 (m, 401 100% 4H), 2.49 (d, J = 1.9 Hz, 3H), 1.92 1.83 (m, 4H). 138 [00206] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (s, 1H), 11.97 (s, 1H), 10.74 (s, 1H), 7.87 7.82 (m, 1H), 7.80 (s, 1H), 7.63 7.56 (m, 1H), 7.49 (td, J = 7.7, 1.3 Hz, 1H), 7.23 7.18 (m, 1H), 7.17 7.11 (m, 2H), 7.05 (dd, J = 8.2, 2.0 Hz, 1H), 514 98% 7.01 (s, 1H), 3.92 3.77 (m, 2H), 2.54 (s, 3H), 0.69 (td, J = 7.1, 0.8 Hz, 3H). 139 [00207] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (s, 1H), 11.96 (s, 1H), 10.79 (s, 1H), 7.78 (d, J = 5.4 Hz, 2H), 7.67 (t, J = 7.5 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.26 (d, J = 7.5 Hz, 1H), 7.21 7.14 (m, 2H), 7.05 6.99 (m, 2H), 2.52 (s, 3H). 510 98% 140 [00208] M1, M2, M3 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 11.99 (s, 1H), 10.94 (s, 1H), 8.46 (d, J = 5.2 Hz, 1H), 7.81 (s, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.24 (t, J = 2.4 Hz, 2H), 7.18 (d, J = 5.3 Hz, 1H), 7.14 457 100% 7.06 (m, 1H), 7.02 (s, 1H), 2.55 (s, 3H), 1.35 (s, 3H). 141 [00209] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.11 (s, 1H), 11.99 (s, 1H), 10.66 (s, 1H), 7.79 (s, 1H), 7.41 (d, J = 8.6 Hz, 1H), 7.16 (s, 1H), 7.07 7.01 (m, 1H), 6.84 (dd, J = 8.6, 2.8 446 100% Hz, 1H), 2.21 (s, 3H). 142 [00210] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.79 (d, J = 0.3 Hz, 1H), 7.25 (d, J = 0.3 Hz, 1H), 7.05 (s, 4H), 2.77 (p, J = 6.9 Hz, 1H), 1.13 (d, J = 6.9 Hz, 6H). 394 94% 143 [00211] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.95 (s, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.36 7.31 (m, 1H), 7.26 (s, 1H), 7.19 (ddt, J = 8.7, 1.7, 0.9 Hz, 1H). 454 95% 144 [00212] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 12.01 (s, 1H), 11.00 (s, 1H), 7.81 (s, 1H), 7.61 (d, J = 8.8 Hz, 1H), 7.26 (d, J = 2.5 Hz, 1H), 7.17 (s, 1H), 6.96 (dd, J = 8.7, 464 100% 2.6 Hz, 1H). 145 [00213] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.83 (s, 1H), 7.24 (s, 1H), 6.92 (p, J = 0.6 Hz, 2H), 2.26 (t, J = 0.6 Hz, 6H). 460 100% 146 [00214] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.88 (s, 1H), 7.62 (d, J = 8.7 Hz, 1H), 7.24 (d, J = 2.5 Hz, 2H), 7.11 (dd, J = 8.7, 2.3 Hz, 1H), 6.83 (d, J = 3.3 Hz, 1H), 6.08 (dp, J = 2.1, 466 100% 1.4, 1.0 Hz, 1H), 2.31 2.27 (m, 3H). 147 [00215] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.52 (d, J = 6.3 Hz, 1H), 7.16 7.10 (m, 2H), 7.08 7.01 (m, 2H), 6.94 (d, J = 10.4 Hz, 1H). 420 98% 148 [00216] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.62 (d, J = 6.4 Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.31 (d, J = 2.5 Hz, 1H), 7.05 6.93 (m, 2H). 448 99% 149 [00217] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.93 (s, 1H), 10.88 (s, 1H), 7.72 (d, J = 1.5 Hz, 1H), 7.60 (dd, J = 8.8, 1.5 Hz, 1H), 7.23 (t, J = 2.1 Hz, 1H), 7.06 (d, J = 458 100% 1.5 Hz, 1H), 6.92 (dt, J = 8.8, 2.0 Hz, 1H), 2.99 2.88 (m, 2H), 1.14 (td, J = 7.4, 1.5 Hz, 3H). 150 [00218] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.20 (s, 1H), 11.99 (s, 1H), 11.19 (s, 1H), 8.77 8.69 (m, 2H), 7.68 7.60 (m, 3H), 7.43 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 2.2 Hz, 1H), 7.19 (dd, J = 8.4, 2.2 447 98% Hz, 1H), 7.01 (d, J = 10.6 Hz, 1H). 151 [00219] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.76 (s, 1H), 7.21 (s, 1H), 6.98 (q, J = 8.5 Hz, 4H), 3.87 (p, J = 6.8 Hz, 1H), 2.50 2.40 (m, 2H), 1.54 (h, J = 7.4 Hz, 2H), 1.21 (d, J = 6.8 Hz, 6H), 0.86 (t, 400 98% J = 7.3 Hz, 3H). 152 [00220] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.87 (s, 1H), 7.50 (s, 1H), 7.48 (d, J = 2.2 Hz, 1H), 7.23 (s, 2H), 7.21 (s, 1H), 3.89 (p, J = 6.8 Hz, 1H), 1.22 (d, J = 6.8 Hz, 6H). 426 100% 153 [00221] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.92 (s, 1H), 11.88 (s, 1H), 10.24 (s, 1H), 7.68 (s, 1H), 7.15 (s, 1H), 6.90 (d, J = 1.1 Hz, 4H), 3.79 (p, J = 6.6 Hz, 1H), 1.76 (tt, J = 8.3, 5.0 Hz, 1H), 1.10 (d, 400 95% J = 6.7 Hz, 6H), 0.87 0.78 (m, 2H), 0.55 0.48 (m, 2H). 154 [00222] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.95 (s, 1H), 11.92 (s, 1H), 10.91 (s, 1H), 7.72 (s, 1H), 7.61 (d, J = 8.7 Hz, 1H), 7.24 (d, J = 2.5 Hz, 1H), 7.18 (s, 1H), 6.92 (dd, J = 8.8, 2.6 Hz, 1H), 3.76 (p, 472 100% J = 6.7 Hz, 1H), 1.11 (d, J = 6.7 Hz, 6H). 155 [00223] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.14 (s, 1H), 12.04 (s, 1H), 10.86 (s, 1H), 8.76 8.71 (m, 2H), 7.89 (s, 1H), 7.67 (d, J = 5.6 Hz, 2H), 7.25 7.17 (m, 2H), 7.09 7.01 (m, 2H), 2.20 (s, 3H). 443 100% 156 [00224] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.87 (s, 1H), 7.55 (t, J = 1.7 Hz, 1H), 7.28 (dd, J = 1.6, 0.9 Hz, 1H), 7.25 (s, 1H), 6.89 (p, J = 0.6 Hz, 2H), 6.25 (dd, J = 1.8, 0.9 Hz, 1H), 2.01 (s, 6H). 444 100% 157 [00225] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 8.85 8.81 (m, 2H), 7.92 (s, 1H), 7.82 7.78 (m, 2H), 7.27 (s, 1H), 7.00 (q, J = 0.6 Hz, 2H), 1.98 (s, 6H). 455 100% 158 [00226] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.15 (s, 1H), 11.95 (s, 1H), 10.93 (s, 1H), 7.68 7.56 (m, 2H), 7.22 (d, J = 2.2 Hz, 1H), 7.12 (dd, J = 8.7, 2.3 Hz, 1H), 6.97 (d, J = 10.6 448 91% Hz, 1H), 6.86 (d, J = 3.4 Hz, 1H), 6.23 6.17 (m, 1H), 2.29 (s, 3H). 159 [00227] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.97 (s, 1H), 11.95 (s, 1H), 11.04 (s, 1H), 8.70 8.65 (m, 2H), 7.79 (s, 1H), 7.55 (d, J = 5.2 Hz, 2H), 7.39 (dd, J = 8.5, 1.3 Hz, 1H), 7.25 (d, J = 2.0 Hz, 1H), 471 100% 7.20 (s, 1H), 7.12 (ddd, J = 8.5, 2.2, 0.7 Hz, 1H), 3.87 3.75 (m, 1H), 1.14 (d, J = 6.7 Hz, 6H). 160 [00228] M1, M2 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 7.67 (d, J = 6.4 Hz, 1H), 7.50 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 6.97 (d, J = 10.4 Hz, 1H). 402 98% 161 [00229] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.97 11.90 (m, 2H), 10.80 (s, 1H), 7.98 (s, 1H), 7.75 (s, 1H), 7.70 (t, J = 1.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.17 (s, 2H), 7.01 (d, J = 8.6 Hz, 1H), 6.77 (dt, J = 460 100% 1.6, 0.7 Hz, 1H), 3.86 3.74 (m, 1H), 1.13 (d, J = 6.7 Hz, 6H). 162 [00230] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 11.91 (s, 1H), 10.59 (s, 1H), 7.55 (d, J = 6.5 Hz, 1H), 6.95 (d, J = 10.6 Hz, 1H), 6.90 (s, 2H), 2.21 (s, 6H). 442 97% 163 [00231] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 11.92 (s, 1H), 10.65 (s, 1H), 7.54 (d, J = 6.6 Hz, 1H), 7.41 (d, J = 8.6 Hz, 1H), 7.05 (d, J = 2.7 Hz, 1H), 6.95 (d, J = 10.6 428/426 96% Hz, 1H), 6.85 (dd, J = 8.6, 2.7 Hz, 1H), 2.21 (s, 3H). 164 [00232] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.08 (br. s, 1H), 11.91 (br. s, 1H), 10.31 (br. s, 1H), 7.52 (d, J = 6.6 Hz, 1H), 6.95 (d, J = 10.5 Hz, 1H), 6.87 (d, J = 8.1 Hz, 1H), 6.82 388 100% 6.75 (m, 2H), 2.56 (d, J = 4.0 Hz, 4H), 1.63 (p, J = 3.3 Hz, 4H). 165 [00233] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.19 (s, 1H), 11.99 (s, 1H), 11.45 (br. s, 1H), 7.73 (d, J = 8.7 Hz, 1H), 7.64 (d, J = 6.6 Hz, 1H), 7.33 (d, J = 2.2 Hz, 1H), 7.19 (dd, J = 436 100% 8.8, 2.1 Hz, 1H), 7.00 (d, J = 10.7 Hz, 1H). 166 [00234] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.15 (s, 1H), 11.94 (s, 1H), 10.50 (s, 1H), 7.70 (d, J = 1.7 Hz, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.59 7.49 (m, 1H), 6.98 (d, J = 10.4 Hz, 1H), 6.84 (s, 2H), 6.38 428 95% (d, J = 1.8 Hz, 1H), 1.98 (s, 6H). 167 [00235] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.17 (s, 1H), 11.96 (s, 1H), 10.69 (s, 1H), 8.73 (d, J = 5.3 Hz, 2H), 7.63 (d, J = 6.5 Hz, 1H), 7.44 (d, J = 5.3 Hz, 2H), 7.00 (d, J = 10.6 Hz, 1H), 6.90 (s, 2H), 439 100% 1.88 (s, 6H). 168 [00236] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.13 (s, 1H), 11.93 (s, 1H), 10.56 (s, 1H), 7.77 (t, J = 1.2 Hz, 1H), 7.68 (t, J = 1.7 Hz, 1H), 7.57 (d, J = 6.5 Hz, 1H), 7.22 (d, J = 8.3 414 96% Hz, 1H), 7.02 6.92 (m, 3H), 6.69 (dd, J = 1.8, 0.9 Hz, 1H), 2.24 (s, 3H). 169 [00237] M1, M2, M3 .sup.1H NMR (400 MHz, Methanol-d.sub.4) 8.75 (d, J = 6.4 Hz, 2H), 7.93 7.86 (m, 2H), 7.69 (d, J = 6.4 Hz, 1H), 7.27 (d, J = 9.0 Hz, 1H), 7.19 (dd, J = 6.1, 2.4 Hz, 2H), 7.00 (d, J = 10.4 Hz, 1H), 425 100% 2.29 (s, 3H). 170 [00238] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (s, 1H), 11.99 (s, 1H), 10.39 (s, 1H), 7.78 (d, J = 0.8 Hz, 1H), 7.17 (d, J = 0.8 Hz, 1H), 7.05 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 8.5 Hz, 2H), 2.39 2.27 (m, 1H), 1.73 1.63 (m, 5H), 1.35 1.18 (m, 5H). 434 98% 171 [00239] commercial 894918-88-8 172 [00240] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (br. s, 1H), 11.96 (br. s, 1H), 10.78 (br. s, 1H), 7.86 (s, 1H), 7.82 7.73 (m, 2H), 7.70 (d, J = 8.2 Hz, 1H), 7.51 (d, J = 2.2 Hz, 402 100% 1H), 7.47 7.32 (m, 2H), 7.30 (dd, J = 8.8, 2.2 Hz, 1H), 7.14 (s, 1H). 173 [00241] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 12.00 (s, 1H), 10.42 (s, 1H), 7.79 (s, 1H), 7.27 7.16 (m, 3H), 7.03 6.96 (m, 2H), 1.17 (s, 9H). 408 100% 174 [00242] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.97 (s, 1H), 10.29 (s, 1H), 7.76 (s, 1H), 7.16 (s, 1H), 6.86 (d, J = 8.2 Hz, 1H), 6.83 6.74 (m, 2H), 2.59 2.52 (m, 4H), 406 97% 1.62 (h, J = 3.1 Hz, 4H). 175 [00243] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (br. s, 1H), 11.93 (br. s, 1H), 10.30 (br. s, 1H), 7.78 (s, 1H), 7.26 (t, J = 7.6 Hz, 1H), 7.10 (d, J = 7.5 Hz, 1H), 7.00 (s, 1H), 6.81 (d, J = 12.5 Hz, 4H), 450 100% 2.53 (s, 3H), 2.28 (s, 3H), 1.83 (s, 6H). 176 [00244] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.96 (s, 1H), 10.84 (s, 1H), 7.78 (s, 1H), 7.42 7.30 (m, 5H), 7.27 (d, J = 8.4 Hz, 1H), 7.21 (d, J = 3.6 Hz, 2H), 7.07 (d, J = 8.0 Hz, 1H), 3.89-3.73 (m, 470 92% 1H), 1.14 (d, J = 6.7 Hz, 6H). 177 [00245] commercial 931964-86-2 178 [00246] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.97 (s, 1H), 11.96 (s, 1H), 10.91 (s, 1H), 7.79 (s, 1H), 7.44 7.41 (m, 2H), 7.38 (dd, J = 2.0, 1.0 Hz, 1H), 7.34 7.26 (m, 2H), 7.24 7.19 (m, 2H), 7.08 504 100% (dd, J = 8.4, 2.3 Hz, 1H), 3.82 (p, J = 6.9 Hz, 1H), 1.14 (d, J = 6.7 Hz, 6H). 179 [00247] commercial 894921-04-1 180 [00248] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.58 (s, 1H), 6.99 (d, J = 0.9 Hz, 1H), 6.91 6.82 (m, 2H), 6.79 6.70 (m, 2H), 3.66 3.59 (m, 5H), 2.97 2.90 (m, 4H), 2.48 2.43 (m, 3H). 417 99% 181 [00249] commercial 894917-28-3 182 [00250] M1, M2, M3 + hydrolysis .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.12 11.79 (m2H), 10.48 (br. s, 1H), 7.78 (d, J = 1.3 Hz, 1H), 7.62 (dt, J = 7.7, 1.4 Hz, 1H), 7.47 (tt, J = 7.6, 1.3 Hz, 1H), 7.36 (tt, J = 7.6, 1.3 Hz, 1H), 7.25 452 93% (dd, J = 7.8, 1.2 Hz, 1H), 7.17 (dd, J = 8.3, 1.1 Hz, 2H), 7.08 7.01 (m, 2H), 6.99 (s, 1H), 2.53 2.50 (m, 3H). 183 [00251] commercial 894919-92-7 184 [00252] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.93 (s, 1H), 10.27 (s, 1H), 7.76 (s, 1H), 7.55 (s, 1H), 7.25 (d, J = 0.7 Hz, 1H), 6.98 (s, 1H), 6.79 (s, 2H), 3.82 (s, 3H), 2.52 (s, 3H), 1.96 (s, 6H). 440 100% 185 [00253] commercial 894918-00-4 186 [00254] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.00 (br. s, 1H), 11.87 (s, 1H), 8.73 (dd, J = 4.3, 1.6 Hz, 1H), 8.18 8.09 (m, 2H), 7.88 (d, J = 8.8 Hz, 1H), 7.78 (s, 1H), 7.50 (d, J = 8.6 383 100% Hz, 2H), 7.43 (dd, J = 8.3, 4.2 Hz, 1H), 6.95 (s, 1H), 2.53 (s, 3H). 187 [00255] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.92 (s, 1H), 10.41 (s, 1H), 7.78 (s, 1H), 6.99 (s, 1H), 6.81 (s, 2H), 6.76 (dt, J = 3.3, 1.2 Hz, 1H), 6.59 6.49 (m, 1H), 2.52 426 100% (s, 3H), 2.42 (d, J = 1.1 Hz, 3H), 1.96 (s, 6H). 188 [00256] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.94 (s, 1H), 10.48 (s, 1H), 7.79 (s, 1H), 7.44 (d, J = 1.8 Hz, 1H), 6.99 (s, 1H), 6.85 (s, 2H), 6.04 (d, J = 1.9 Hz, 1H), 2.52 (s, 3H), 1.84 (s, 6H). 440 94% 189 [00257] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (s, 1H), 11.96 (s, 1H), 10.94 (s, 1H), 8.62 (d, J = 2.3 Hz, 1H), 8.50 (d, J = 1.9 Hz, 1H), 7.96 (t, J = 2.1 Hz, 1H), 7.81 (s, 1H), 7.39 (d, J = 8.4 Hz, 1H), 477 100% 7.26 (d, J = 2.2 Hz, 1H), 7.11 (dd, J = 8.5, 2.2 Hz, 1H), 7.02 (s, 1H), 2.54 (s, 3H). 190 [00258] described .sup.1H NMR (500 MHz, DMSO-d.sub.6) 12.27 (br. s, 2 H), 10.87 (s, 1 H), 7.86 (s, 1 H), 7.59 (s, 1 H), 7.29 (d, J = 8.9 Hz, 2 H), 7.18 (d, J = 8.9 Hz, 2 H). 470 98% 191 [00259] Nitration, M2 .sup.1H NMR (700 MHz, DMSO-d.sub.6) 12.34 (s, 1 H), 12.30 (s, 1 H), 10.84 (s, 1 H), 7.69 (s, 1 H), 7.62 (s, 1 H), 7.32 (d, J = 9.1 Hz, 2 H), 7.23 (d, J = 9.1 Hz, 2 H). 447 95% 192 [00260] M1, M2 .sup.1H NMR (500 MHz, DMSO-d.sub.6) 12.20 11-99 (m, 2 H), 10.74 (s, 1 H), 7.73 (s, 1 H), 7.28 (d, J = 9.0 Hz, 2 H), 7.21 (s, 1 H), 7.17 (d, J = 9.0 Hz, 2 H). 486 100% 193 [00261] M1, M2 .sup.1H NMR (500 MHz, DMSO-d.sub.6) 12.01 (s, 1 H), 11.83 (s, 1 H), 10.24 (s, 1 H), 7.60 (s, 1 H), 7.24 (d, J = 9.1 Hz, 2 H), 7.17 (d, J = 9.1 Hz, 2 H), 6.78 (s, 1 H), 3.80 (s, 3 H). 432 99% 194 [00262] described .sup.1H NMR (500 MHz, DMSO-d.sub.6) 11.93 (s, 1 H), 11.90 (s, 1 H), 10.64 (s, 1 H), 7.76 (s, 1 H), 7.26 (d, J = 9.1 Hz, 2 H), 7.14 (d, J = 9.1 Hz, 2 H), 6.71 (s, 1 H), 2.63 2.55 (m, 1 H), 1.10 1.04 (m, 2 442 100% H), 0.60 0.55 (m, 2 H). 195 [00263] M1, M2 .sup.1H NMR (500 MHz, DMSO-d.sub.6) 7.87 (s, 1 H), 7.38 (s, 1 H), 7.24 (d, J = 8.8 Hz, 2 H), 7.01 (d, J = 8.8 Hz, 2 H), 1.18 (s, 9 H). 452 100% 196 [00264] M1, (M4, M5), M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.91 (s, 1H), 10.10 (s, 1H), 7.65 (s, 1H), 7.06 6.96 (m, 2H), 6.93 6.76 (m, 2H), 3.22 3.12 (m, 4H), 2.50 (s, 3H), 435 100% 1.87 1.75 (m, 4H). 197 [00265] M1, M2 .sup.1H NMR (500 MHz, DMSO-d.sub.6) 12.14 (s, 1H), 12.12 (s, 1H), 10.96 (s, 1H), 7.77 (s, 1H), 7.41 7.36 (m, 2H), 7.32 (d, J = 8.4 Hz, 1H), 7.29 7.22 (m, 4H), 7.11 (dd, J = 8.4, 2.2 Hz, 1H). 530 100% 198 [00266] M1/M3, M2 462 98% 199 [00267] M1/M3, M2 482 99% 200 [00268] M1, (M4, M5), M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.06 (s, 1H), 11.92 (s, 1H), 10.39 (s, 1H), 7.69 (s, 1H), 7.10 (d, J = 2.5 Hz, 1H), 7.04 6.93 (m, 3H), 3.68 3.63 (m, 4H), 2.86 2.78 (m, 4H). 451 100% 201 M1, (M4, M5), M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.95 (s, 1H), 10.48 (s, 1H), 7.72 (s, 1H), 7.14 (d, J = 8.8 Hz, 1H), 7.10 (d, J= 2.4 Hz, 1H), 7.00 (s, 1H), 6.98-6.95 (m, 1H), 3.76-3.59 (m, 465 97% 3H), 3.26-3.19 (m, 2H), 2.90 (d, J = 12.0 Hz, 1H), 2.57-2.54 (m, 4H), 0.66 (d, J = 6.0 Hz, 3H). 202 [00269] Different route to 6Q 479 99% 203 [00270] M1, M2, M3 + TIPS deprot. 467 98% 204 [00271] M1, (M4, MS), M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.08 (s, 1H), 11.93 (s, 1H), 10.39 (s, 1H), 7.70 (s, 1H), 7.11 (d, J = 2.5 Hz, 1H), 7.06 6.93 (m, 3H), 3.81 (ddd, J = 11.1, 3.1, 1.7 Hz, 1H), 3.74 3.44 (m, 5H), 465 98% 2.99 (ddt, J = 16.4, 11.5, 2.1 Hz, 2H), 2.62 (td, J = 11.4, 3.0 Hz, 1H), 2.34 (dd, J = 11.4, 9.7 Hz, 1H), 1.06 (d, J = 6.2 Hz, 3H). 205 [00272] M1/M3, M2 478 99% 206 [00273] M1/M3, M2 497 99% 207 [00274] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.85 (s, 1H), 9.98 (s, 1H), 8.20 (d, J = 0.7 Hz, 1H), 7.75 7.68 (m, 2H), 7.60 (s, 1H), 7.48 7.37 (m, 3H), 7.27 (t, J = 7.4 Hz, 1H), 7.01 (s, 1H), 2.53 (s, 3H). 398 100% 208 [00275] M1, (M4, MS), M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.94 (s, 1H), 10.35 (s, 1H), 7.70 (s, 1H), 7.12 7.04 (m, 2H), 7.00 (s, 1H), 6.92 (dd, J = 8.8, 2.6 Hz, 1H), 3.79 3.66 (m, 4H), 3.13 3.05 (m, 465 98% 4H), 2.56 (s, 3H), 1.90 (p, J = 5.9 Hz, 2H). 209 [00276] M1/M3, M2 495 98% 210 [00277] M1/M3, M2 475 100% 211 [00278] M1/M3, M2 493 100% 212 [00279] M1, M2b, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.97 (s, 1H), 8.09 (s, 1H), 7.89 (s, 1H), 7.51 7.40 (m, 2H), 7.33 7.24 (m, 2H), 7.20 7.12 (m, 1H), 7.01 (s, 1H), 2.56 (s, 3H). 461 91% 213 [00280] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 11.96 (s, 1H), 11.20 (s, 1H), 8.37 (d, J = 2.3 Hz, 1H), 7.82 (s, 1H), 7.68 7.44 (m, 5H), 7.05 (s, 1H), 2.57 (s, 3H). 475 100% 214 [00281] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 11.96 (s, 1H), 11.20 (s, 1H), 8.36 (d, J = 2.2 Hz, 1H), 7.85 7.78 (m, 2H), 7.67 7.60 (m, 2H), 7.49 (t, J = 9.0 Hz, 1H), 7.05 (s, 1H), 2.56 (s, 3H). 495 100% 215 [00282] M1, M2, M3 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.12 (s, 1H), 11.96 (s, 1H), 11.14 (s, 1H), 8.35 (d, J = 2.3 Hz, 1H), 7.81 (s, 1H), 7.64 (ddd, J = 12.7, 6.4, 2.2 Hz, 3H), 7.34 7.23 (m, 2H), 7.05 (s, 1H), 2.56 (s, 461 100% 3H). 216 [00283] M2, different route 427 100% 217 [00284] 12D, M1, M2 419 100% 218 [00285] M2 different route 452 100% 219 [00286] M1, M2, M3 508 99% 220 [00287] M1, M2, M3 482 98% 221 [00288] described .sup.1H-NMR (500 MHz, DMSO-d.sub.6) 11.98 (s, 1H), 11.93 (s, 1H), 10.13 (s, 1H), 7.68 (s, 1H), 7.24-7.20 (m, 2H), 7.20-7.17 (m, 2H), 7.08 (s, 1H), 2.56 (s, 6H). 445 98% 222 [00289] M1, M2b .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.96 (s, 1H), 11.49 (s, 1H), 8.20 (d, J = 2.7 Hz, 1H), 7.86 (d, J = 1.3 Hz, 1H), 7.80 (d, J = 9.1 Hz, 7.05 (d, J = 9.1 Hz, 417 99% 1H), 6.99 (s, 1H), 2.53 (s, 3H). 223 [00290] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.10 (s, 1H), 11.91 (s, 1H), 10.85 (s, 1H), 8.04 (d, J = 2.8 Hz, 1H), 7.71 (s, 1H), 7.64 (dd, J = 8.8, 2.8 Hz, 1H), 7.24 (d, J = 8.8 Hz, 1H), 417 100% 7.03 (s, 1H), 2.52 (s, 3H). 224 [00291] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.93 (s, 1H), 10.78 (s, 1H), 8.40 (d, J = 2.6 Hz, 1H), 8.02 7.93 (m, 2H), 7.90 7.85 (m, 1H), 7.77 (d, J = 2.2 Hz, 1H), 7.53 (dt, J = 8.7, 2.5 Hz, 409 100% 1H), 7.48 7.41 (m, 2H), 7.41 7.35 (m, 1H), 7.02 (s, 1H), 2.56 (d, J = 2.2 Hz, 3H). 225 [00292] M1/M3, M2 504 97% 226 [00293] M1, M2b .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.95 (s, 1H), 11.63 (s, 1H), 8.36 (s, 1H), 7.84 (s, 1H), 7.15 (s, 1H), 6.99 (s, 1H), 2.52 (s, 3H). 445 91% 227 [00294] M1, M2, M3 511 94% 228 [00295] M1, M2 .sup.1H NMR (500 MHz, DMSO-d.sub.6) 12.03 (s, 1H), 11.86 (s, 1H), 9.89 (s, 1H), 7.60 (s, 1H), 7.28 7.25 (m, 2H), 7.22 (d, J = 2.0 Hz, 1H), 6.97 (s, 1H), 6.87 (dd, J = 8.7, 2.0 Hz, 1H), 6.30 (dd, J = 3.0, 0.8 Hz, 1H), 3.70 385 100% (s, 3 H), 2.52 (s, 3H). 229 [00296] M1, M2, M3 493 95% 230 [00297] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.91 (s, 1H), 8.66 (s, 1H), 7.73 (s, 1H), 7.27 7.11 (m, 3H), 7.16 7.05 (m, 2H), 7.01 (d, J = 0.8 Hz, 1H), 2.51 (s, 3H), 398 96% 1.95 (d, J = 0.6 Hz, 6H). 231 [00298] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.96 (s, 1H), 11.17 (s, 1H), 8.87 (dd, J = 4.6, 1.8 Hz, 1H), 8.45 (d, J = 8.2 Hz, 1H), 7.97 (d, J = 8.9 Hz, 1H), 7.85 (s, 1H), 7.64 (d, J = 2.1 383 100% Hz, 1H), 7.52 (dd, J = 8.3, 4.6 Hz, 1H), 7.44 (dt, J = 9.0, 2.1 Hz, 1H), 6.97 (s, 1H), 2.54 (d, J = 1.9 Hz, 3H). 232 [00299] M1, M2, M3 507 99% 233 [00300] M1, M2, M3 493 96% 234 [00301] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.04 (s, 1H), 11.92 (s, 1H), 10.56 (s, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.77 (d, J = 4.4 Hz, 1H), 7.64 7.56 (m, 1H), 7.12 (dt, J = 8.6, 2.2 403 97% Hz, 1H), 6.98 (s, 1H), 2.73 (d, J = 4.2 Hz, 3H), 2.54 (s, 3H). 235 [00302] M1, M2, M3 493 90% 236 [00303] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.95 (s, 1H), 11.64 (s, 1H), 8.36 (s, 1H), 7.84 (s, 1H), 7.14 (s, 1H), 6.99 (s, 1H), 2.52 (s, 3H). 445 100% 237 [00304] described 1H-NMR (500 MHz, DMSO-d.sub.6) 12.07 (br. s, 1H), 11.97 (br. s, 1H), 7.42 (s, 1H), 7.35 (mc, 2H), 7.29 (mc, 2H), 6.99 (s, 1H), 4.29 (mc, 2H), 4.09 (mc, 2H). 444 95% 238 [00305] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 13.17 (s, 1H), 12.06 (s, 1H), 11.96 (d, J = 4.2 Hz, 1H), 7.84 7.75 (m, 2H), 7.39 (t, J = 7.4 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 7.25 (t, 389 99% J = 7.5 Hz, 1H), 7.02 (s, 1H), 2.54 (d, J = 2.6 Hz, 3H). 239 [00306] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.05 (s, 1H), 11.88 (s, 1H), 10.52 (s, 1H), 7.75 (d, J = 8.7 Hz, 1H), 7.73 7.64 (m, 2H), 7.16 (dd, J = 8.8, 2.3 Hz, 1H), 6.98 (s, 1H), 2.72 403 99% (s, 3H), 2.52 (s, 3H). 240 [00307] M1, M2 .sup.1H NMR (400 MHz, DMSO-d.sub.6) 12.76 (s, 1H), 12.03 (s, 1H), 11.90 (s, 1H), 7.78 (s, 1H), 7.50 7.34 (m, 5H), 7.01 (s, 1H), 2.55 (s, 3H), 2.20 (s, 3H). 429 100% 241 [00308] M1, M2 .sup.1H NMR (500 MHz, DMSO-d.sub.6) 12.09 (s, 1H), 11.90 (s, 1H), 10.56 (s, 1H), 7.67 (s, 1H), 7.28 (d, J = 8.7 Hz, 1H), 7.08 (d, J = 2.1 Hz, 1H), 7.00 (s, 1H), 6.82 (dd, J = 8.7, 412 100% 2.1 Hz, 1H), 2.51 (s, 3H). 242 [00309] M1, M2 .sup.1H NMR (500 MHz, DMSO-d.sub.6) 12.07 (s, 1H), 11.92 (s, 1H), 10.06 (s, 1H), 7.66 (s, 1H), 6.99 (s, 1 H), 6.70 (d, J = 8.7 Hz, 1H), 6.56 (d, J = 2.5 Hz, 1H), 6.50 (dd, J = 390 100% 8.7, 2.5 Hz, 1H), 4.19- 4.10 (m, 4H), 2.50 (s, 3 H). 243 [00310] M1, (M4, MS), M2 .sup.1H NMR (400 MHz) 8 12.07 (s, 1H) 11.95 (s, 1H), 10.48 (s, 1H), 7.72 (s, 1H), 7.19 7.07 (m, 2H), 7.02 6.92 (m, 2H), 3.79 3.56 (m, 3H), 3.29 3.18 (m, 2H), 2.95 2.87 (m, 1H), 2.59 465 99% 2.50 (m, 4H), 0.66 (d, J = 5.8 Hz, 3H). 244 [00311] M1/M3, M2 502 97% 245 [00312] M1, M2, M3 485 99% 246 [00313] M1, M2, M3 470 99% 247 [00314] M1, M2, M3 484 98% 248 [00315] M1, M2, M3 468 98% 249 [00316] M1, M2, M3 482 98% 250 [00317] M1, M2 with aniline 1T 511 99% 251 [00318] described 454 99% 252 [00319] M1/1V + M3, M2 + TIPS deprot. 430 99% 253 [00320] M1/1V + M3, M2 + TIPS deprot. 455 99% 254 [00321] M1, M2, M3 466 99% 255 [00322] M1, M2 with aniline 2T 469 99% 256 [00323] M1, M2, M3 481 91% 257 [00324] M1, M2, M3 508 97% 258 [00325] M1, M2, M3 500 96% 259 [00326] M1, M2, M3 498 98% 260 [00327] M1, M2, M3 474 97% 261 [00328] M1, M2, M3 488 98% 262 [00329] M1, M2, M3 536 97% 263 [00330] M1, M4, M5, M2 431 98% 264 [00331] M1, M4, M5, M2 433 98% 265 [00332] M1, M4, M5, M2 397 97% 266 [00333] M1, M2, M3 468 98% 267 [00334] M1, M2, M3 473 99% 268 [00335] M1, M2, M3 496 99% 269 [00336] M1, M2, M3 495 99% 270 [00337] M1, M2, M3 479 98% 271 [00338] M1, M2, M3 479 99% 272 [00339] M1, M2, M3 495 99% 273 [00340] M1, M2, M3 480 98% 274 [00341] M1/M3, M2 446 446 99% 275 [00342] M1, M2, M3 509 97% 276 [00343] As for cpd. 221 498 99% 277 [00344] M1, M2, M3 524 98% 278 [00345] As for cpd. 221 444 97% 279 [00346] M1/M3, M2 478 98% 280 [00347] M1, M2, M3 457 98% 281 [00348] As for cpd. 221 459 99% 282 [00349] M1, M2, M3 488 98% 283 [00350] M1/M3, M2 496 98% 284 [00351] 274 + hydrog. 446 96% 285 [00352] M1, M4, MS, M2 432 99% 286 [00353] M1, M2, M3 488 98% 287 [00354] M1, M2, M3 520 98% 288 [00355] M1, M2, M3 485 97% 289 [00356] M1, M2, M3 495 98% 290 [00357] M1, M2, M3 471 96% 291 [00358] M1, M2, M3 501 99% 292 [00359] M1, M4, MS, M2 396 98% 293 [00360] M1, M2, M3 434 98% 294 [00361] M1/M3, M2 496 99% 295 [00362] M1, M2, M3 478 96% 296 [00363] M1, M2, M3 418 99% 297 [00364] M1, M2, M3 412 98% 298 [00365] M1, M2, M3 511 91% 299 [00366] M1/M3, M2 488 96% 300 [00367] M1/1V + M3, M2 + TIPS deprot. 478 96% 301 [00368] M1/1V+ M3, M2 + TIPS deprot. 469 99% 302 [00369] M1, M2, M3 532 99% 303 [00370] M1, M2, M3 491 96% 304 [00371] 297 + hydrog. 416 99% 305 [00372] M1, M2, M3 468 99% 306 [00373] 299 + hydrog. 490 98% 307 [00374] M1, M2, M3 496 99% 308 [00375] M1, M2, M3 478 98% 309 [00376] M1, M2, M3 476 99% 310 [00377] M1/M3, M2 542 (M + Na).sup.+ 100% 311 [00378] M1, M2, M3 + de- boc 455 99% 312 [00379] M1/M3 + POMez, M2 518 100% 313 [00380] M1/M3, M2 520 96% 314 [00381] M1, M2, M3 484 100% 315 [00382] M1, M2, M3 510 97% 316 [00383] M1, M2, M3 508 98% 317 [00384] M1, M2, M3 508 100% 318 [00385] M1, M2, M3 465 95% 319 [00386] M1, M2, M3 484 97% 320 [00387] M1, M2, M3 488 98% 321 [00388] M1, M2, M3 454 90% 322 [00389] M1, M2 492 100% 323 [00390] M1, M2 428 100% 324 [00391] M1, M2 448 100% 325 [00392] M1, M2 524 100% 326 [00393] M1, M2, M3 492 100% 327 [00394] M1, M2, M3 508 97% 328 [00395] M1, M2, M3 482 100% 329 [00396] M1, M2, M3 513 92% 330 [00397] M1, M2, M3 540 99% 331 [00398] M1, M2, M3 529 95% 332 [00399] M1, M2, M3 526 99% 333 [00400] M1, M2, M3 470 99% 334 [00401] M1, M2, M3 509 89% 335 [00402] M1, M2, M3 547 93% 336 [00403] M1, M2, M3 482 100% 337 [00404] M1, M2, M3 483 98% 338 [00405] M1, M2, M3 496 100% 339 [00406] M1, M2, M3 524 94% 340 [00407] M1, M2, M3 493 98% 341 [00408] M1, M2, M3 497 100% 342 [00409] M1, M2, M3 + de- boc 471 92% 343 [00410] M1, M2, M3 + de- boc 497 96% 344 [00411] M1, M2, M3 490 90% 345 [00412] M1, M2, M3 522 100% 346 [00413] M1, M2, M3 + benzimi- dazole opening 547 93% 347 [00414] M1, M2, M3 517 100% 348 [00415] M1, M2, M3 499 100% 349 [00416] M1, M2, M3 493 100% 350 [00417] M1, M2, M3 495 100% 351 [00418] M1, M2, M3 491 96% 352 [00419] M1, M2, M3 493 100% 353 [00420] M1, M2, M3 497 95% 354 [00421] M1, M2, M3 511 97% 355 [00422] M1, M2, M3 511 96% 356 [00423] M1, M2, M3 525 97% 357 [00424] M1, M2, M3 517 97% 358 [00425] M1, M2, M3 459 100% 359 [00426] M1, M2, M3 482 96% 360 [00427] M1, M2, boronic ester synthesis, M3 510 95% 361 [00428] M1, M2, M3 496 100% 362 [00429] M1, M2 384 100% 363 [00430] M1, M2, M3 537 99% 364 [00431] M1, M2, M3 527 94% 365 [00432] M1, M2, M3 525 100% 366 [00433] M1, M2, M3 490 100% 367 [00434] M1, M2, M3 545 98% 368 [00435] M1, M2, M3 535 100% 369 [00436] M1, M2, M3 513 100% 370 [00437] M1, M2, M3 480 100% 371 [00438] M1, M2, M3 504 97% 372 [00439] M1, M2, M3 462 97% 373 [00440] M1/1V + M3, M2 + TIPS deprot. 487 97% 374 [00441] M1, M2, M3 525 98% 375 [00442] M1/M3, M2 498 97% 376 [00443] M1/M3, M2 467 99% 377 [00444] M1/M3, M2 451 100% 378 [00445] M1/M3, M2 450 98% 379 [00446] As for cpd. 194 487 90% 380 [00447] M1, M2 382 90% 381 [00448] As for cpd. 221 431 96% 382 [00449] As for cpd. 221 458 96% 383 [00450] M1, M2 426 99% 384 [00451] M1, M2 388 99% 385 [00452] M1, (M4, MS), M2 434 100% 386 [00453] M1/M3, M2 + TBS deprot. 480 (M + Na).sup.+ 95% 387 [00454] 120, M1/ M3, M2 463 100% 388 [00455] M1, M2 405 (M + H.sub.2O).sup.+ 98% 389 [00456] M1/M3, M2 525 (M + Na).sup.+ 97% 390 [00457] M1/M3, M2 525 (M + Na).sup.+ 98% 391 [00458] M1, M2 414 97% 392 [00459] 12D, M1/ M3, M2 464 100% 393 [00460] M1/M3, M2 507 (M + Na).sup.+ 91% 394 [00461] M1, M2 398 97% 395 [00462] M1/M3, M2 515 98% 396 [00463] M1, M2 432 98% 397 [00464] M1/M3, M2 503 97% 398 [00465] M1/M3, M2 520 98% 399 [00466] M1, M2 448 100% 400 [00467] M1, M2 416 99% 401 [00468] M1, M2, M3 + TIPS deprot. 498 92%

3. Hemolysin Alpha-Based Ca.SUP.2+.-Influx Assay

[0367] The assay is based on the Fluo-4 NW Calcium Assay Kit (#F.sub.36205) from Thermo Scientific. Here the effect of hemolysin alpha from Staphylococcus aureus was monitored by loading non adherent U397 cells with the Ca.sup.2+-sensitive dye Fluo-4 hemolysin alpha addition leads to the formation of Ca.sup.2+ permissive pores in the membrane of the U397 cells which results in a dose dependent increase of fluorescence.

[0368] Briefly, the protocol described here was applied for screening and activity determination in a low-volume 384-well microtiter plate with cell culture treated surface. For high-throughput application in the 1536-well microtiter plate format, volumes of the reagent mixes were adjusted, maintaining the volumetric ratio. [0369] a. Hemolysin alpha was diluted with PBS from its stock to a working concentration of 35 nM. U937 cells were diluted in assay buffer (HBBS, 20 mM HEPES) to 4000 cells/l. 1 Fluo-4 NW dye loading solution was prepared according to manufacturer's specifications including 5 mM probenecid to reduce background fluorescence. [0370] b. Chemical compounds were applied into empty assay plates using contact-free acoustic droplet-dispensing (Echo520 Labcyte Inc., Sunnyvale CA) from 10 mM compound stocks in 100% DMSO, to a final concentration of 10 UM or in serial dilution series of the required concentration range. Equal amounts of DMSO without any compound were added to control samples. [0371] c. 5 L of the U937 cells+5 l of 1 Fluo-4 NW dye load were dispensed using a Multidrop dispenser (Thermo Fisher Scientific, Waltham MA) into the wells of a microtiter plate. The plate was centrifuged at 1000 rpm and incubated at 37 C. for 30 min followed by an incubation step at r. t. for another 30 min. [0372] d. The reaction was started by addition of 4 l of hemolysin alpha to a final concentration of 10 nM followed by a centrifugation step for 1 min at 1000 rpm. No hemolysin alpha was added to negative control samples. [0373] e. After incubation at room temperature for 4 h the generated signal was measured with an EnVision plate reader (Perkin Elmer, Waltham MA), using excitation at 485 nm and an emission at 535 nm.

4. LDH-Glo Cytotoxicity Assay

[0374] The LDH-Glo-Cytotoxicity Assay is a bioluminescent plate-based assay to quantify the release of cellular Lactate Dehydogenase (LDH) into the assay medium upon plasma membrane damage by hemolysin treatment of the cells. LDH in the supernatant reduces an added substrate to generate luciferin which is converted into a bioluminescent signal by the Ultra Glo Luciferase (Promega).

[0375] A549-Cells (DSMZ, #ACC107), that are used for the assay, are maintained in RPMI 1640 cell culture medium+glutamine (PAN Biotech GmbH, Aidenbach, Germany; #P04-22100; P04-05500) supplemented with 10% fetal calf serum (Capricorn, #FBS-11A) and are grown at 37 C., 5% CO.sub.2.

[0376] For the LDH assay compounds or DMSO are prediluted at different concentrations in l cell culture medium RPMI 1640+5% FCS+10 mM HEPES in black uclear 384-well-plates (Greiner BioOne). Shortly afterwards 10 l of 70 nM S. aureus Alpha hemolysin (IBT BIOSERVICES, #1401-002) was added to get a final assay concentration of 20 nM. After adding 10 l of A549 cells (20.000 cells/well diluted in assay medium) the assay plates (total assay volume: 35 l) were incubated for 5 h at 37 C./5% CO.sub.2 in humidified chambers in order to allow hemolysis.

[0377] As a positive internal control, we use the hemolysin antibody (IBT Bioservices, #0210-001) at a concentration range from 0.005-10 g/ml and determine the IC50 concentration. The standard IC50 concentration for the antibody is approximately 50 ng/ml.

[0378] The determination of the LDH concentration was done after the 5 h incubation time according to the instructions of the One Glo Luminescent assay Kit (Promega, cat no. G7891). Shortly, 20 l of cell culture supernatant were incubated in a separated black clear 384-well plate at 25 C. for 20 min, mixed with 20 l of the LDH reagent using an orbital shaker (1 min, 300 rpm) and further incubated for 5 min at 2 C. The reaction was stopped by addition of 10 l stop-reagent, provided with the assay kit. Shortly afterwards the fluorescent signal was measured by Victor X5 plate reader (Perkin Elmer) using the filters 531 nm (extinction) and 590 nm (emission). EC.sub.50 values were calculated with the software Excel Fit (IDBS, Guildford, UK) from 3-fold dilution series comprising at least 8 concentrations in duplicates.

5. Biological Activities of Compounds

[0379] Activities of compounds are listed in Table 3 together with compound number and IUPAC names. Biological activities are determined by two main assays with Hl-induced cell damage: hemolysin- Ca.sup.2+-influx on U937 cells according to Example 3 and LDH-Glo Cytotoxicity Assay on A549 cells according to Example 4, and were grouped according to the following scheme:

TABLE-US-00006 30 nM 100 nM 1 M <30 nM x < 100 nM x < 1 M x < 3.5 M Ca.sup.2+-infux Assay +++ ++ + (+) (IC-50) 30 nM 100 nM 1 M <30 nM x < 100 nM x < 1 M x < 6 M A549-LDH Assay +++ ++ + (+) (IC-50)

TABLE-US-00007 TABLE 3 IUPAC chemical names and biological activities Ca.sup.2+-infux A549-LDH Ex IUPAC Name Assay activity Assay activity 1 N-(2-chloro-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- +++ ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 2 N-(2,3-dichloro-2,4-difluoro-[1,1-biphenyl]-4-yl)-7- +++ + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 3 N-(2-chloro-4-fluoro-[1,1-biphenyl]-4-yl)-7-methyl-2,3- +++ ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 4 N-(2-chloro-3-(dimethylamino)-[1,1-biphenyl]-4-yl)-7- +++ ++ methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 5 N-(2-chloro-2-fluoro-[1,1-biphenyl]-4-yl)-7-methyl-2,3- +++ ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 6 N-(2-chloro-3-(pyrrolidin-1-yl)-[1,1-biphenyl]-4-yl)-7- +++ + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 7 N-(3-chloro-4-(thiophen-3-yl)phenyl)-7-methyl-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 8 N-(2,4-dichloro-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 9 7-chloro-N-(2-chloro-3-(dimethylamino)-[1,1-biphenyl]-4- +++ + yl)-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 10 N-(3-chloro-4-(indolin-6-yl)phenyl)-7-fluoro-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 11 N-(2,3-dichloro-4-fluoro-[1,1-biphenyl]-4-yl)-7-methyl- +++ + 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 12 7-chloro-N-(2-chloro-4-fluoro-[1,1-biphenyl]-4-yl)-2,3- +++ + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 13 N-(3-chloro-4-(indolin-6-yl)phenyl)-7-methyl-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 14 7-chloro-N-(2-chloro-[1,1-biphenyl]-4-yl)-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 15 7-bromo-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4- +++ ++ tetrahydroquinoxaline-6-sulfonamide 16 N-(4-(furan-2-yl)-3,5-dimethylphenyl)-7-methyl-2,3-dioxo- +++ +++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 17 7-methyl-N-(2-methyl-[1,1-biphenyl]-4-yl)-2,3-dioxo- +++ +++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 18 N-(2-chloro-4-fluoro-[1,1-biphenyl]-4-yl)-7-fluoro-2,3- +++ ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 19 7-chloro-N-(2,3-dichloro-4-fluoro-[1,1-biphenyl]-4-yl)-2,3- +++ + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 20 7-ethyl-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4- +++ ++ tetrahydroquinoxaline-6-sulfonamide 21 7-chloro-N-(2-chloro-3-(pyrrolidin-1-yl)-[1,1-biphenyl]-4- +++ + yl)-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 22 N-(3-chloro-4-(furan-3-yl)phenyl)-7-methyl-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 23 N-(2-chloro-3-methyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3- +++ ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 24 N-(3-chloro-4-(thiophen-2-yl)phenyl)-7-methyl-2,3-dioxo- +++ ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 25 7-chloro-N-(2-chloro-2-fluoro-[1,1-biphenyl]-4-yl)-2,3- +++ + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 26 N-(2,3-dichloro-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- +++ ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 27 N-(2-chloro-3-(pyrrolidin-1-yl)-[1,1-biphenyl]-4-yl)-7- +++ (+) fluoro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 28 7-methyl-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4- +++ +++ tetrahydroquinoxaline-6-sulfonamide 29 N-(3-chloro-4-(pyridin-3-yl)phenyl)-7-methyl-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 30 N-(3-chloro-4-(2-chloropyridin-4-yl)phenyl)-7-methyl-2,3- +++ ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 31 7-isopropyl-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)- +++ +++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 32 7-chloro-N-(3-chloro-4-(thiophen-3-yl)phenyl)-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 33 7-fluoro-N-(2-methyl-[1,1-biphenyl]-4-yl)-2,3-dioxo- +++ ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 34 N-(2-chloro-3-(dimethylamino)-[1,1-biphenyl]-4-yl)-7- +++ + fluoro-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 35 7-chloro-N-(2,3-dichloro-[1,1-biphenyl]-4-yl)-2,3-dioxo- +++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 36 N-(2-chloro-2-fluoro-[1,1-biphenyl]-4-yl)-7-fluoro-2,3- +++ + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 37 N-(3-chloro-4-(pyridin-4-yl)phenyl)-7-methyl-2,3-dioxo- +++ ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 38 N-(2-chloro-4-methyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3- ++ + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 39 N-(2-chloro-3-isopropyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3- ++ (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 40 N-(2-chloro-[1,1-biphenyl]-4-yl)-7-fluoro-2,3-dioxo-1,2,3,4- ++ + tetrahydroquinoxaline-6-sulfonamide 41 7-bromo-2,3-dioxo-N-(4-propylphenyl)-1,2,3,4- ++ ++ tetrahydroquinoxaline-6-sulfonamide 42 N-(3,5-dimethyl-4-(thiophen-3-yl)phenyl)-7-methyl-2,3- ++ + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 43 N-(2,3-dichloro-[1,1-biphenyl]-4-yl)-5-fluoro-7-methyl-2,3- ++ (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 44 7-chloro-N-(3-chloro-4-(furan-3-yl)phenyl)-2,3-dioxo- ++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 45 7-chloro-N-(2-methyl-[1,1-biphenyl]-4-yl)-2,3-dioxo- ++ ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 46 7-chloro-N-(3-chloro-4-(indolin-6-yl)phenyl)-2,3-dioxo- ++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 47 7-chloro-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4- ++ ++ tetrahydroquinoxaline-6-sulfonamide 48 7-chloro-N-(3-chloro-4-(pyridin-3-yl)phenyl)-2,3-dioxo- ++ (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 49 7-methyl-2,3-dioxo-N-(4-propylphenyl)-1,2,3,4- +++ ++ tetrahydroquinoxaline-6-sulfonamide 50 7-methyl-2,3-dioxo-N-(4-(trifluoromethyl)phenyl)-1,2,3,4- ++ ++ tetrahydroquinoxaline-6-sulfonamide 51 N-(2-fluoro-2,6-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl- ++ ++ 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 52 N-(3-chloro-4-(5-methylthiophen-2-yl)phenyl)-7-methyl- ++ + 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 53 N-(4-cyclopropylphenyl)-7-methyl-2,3-dioxo-1,2,3,4- ++ +++ tetrahydroquinoxaline-6-sulfonamide 54 7-methyl-2,3-dioxo-N-(5,6,7,8-tetrahydronaphthalen-2-yl)- ++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 55 7-chloro-2,3-dioxo-N-(4-propylphenyl)-1,2,3,4- ++ ++ tetrahydroquinoxaline-6-sulfonamide 56 N-(3-chloro-4-(trifluoromethyl)phenyl)-7-methyl-2,3-dioxo- ++ (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 57 N-(3-chloro-2,6-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl- ++ ++ 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 58 N-(3,5-dimethyl-4-(thiophen-2-yl)phenyl)-7-methyl-2,3- ++ (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 59 N-(3-(dimethylamino)-2,6-dimethyl-[1,1-biphenyl]-4-yl)-7- ++ + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 60 7-methyl-N-(naphthalen-2-yl)-2,3-dioxo-1,2,3,4- ++ ++ tetrahydroquinoxaline-6-sulfonamide 61 N-([1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo-1,2,3,4- +++ ++ tetrahydroquinoxaline-6-sulfonamide 62 N-(3-chloro-4-(3-methylthiophen-2-yl)phenyl)-7-methyl- ++ + 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 63 N-(4-bromo-3-chlorophenyl)-5-fluoro-7-methyl-2,3-dioxo- ++ (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 64 N-([1,1-biphenyl]-4-yl)-7-fluoro-2,3-dioxo-1,2,3,4- ++ + tetrahydroquinoxaline-6-sulfonamide 65 N-(2,3-dichloro-[1,1-biphenyl]-4-yl)-7-fluoro-2,3-dioxo- ++ (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 66 N-(3-chloro-4-(pyrimidin-5-yl)phenyl)-7-methyl-2,3-dioxo- ++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 67 N-(4-cyclopropylphenyl)-7-ethyl-2,3-dioxo-1,2,3,4- ++ ++ tetrahydroquinoxaline-6-sulfonamide 68 N-(4-cyclopropylphenyl)-7-fluoro-2,3-dioxo-1,2,3,4- ++ + tetrahydroquinoxaline-6-sulfonamide 69 N-(3-chloro-4-(5-methylfuran-2-yl)phenyl)-7-methyl-2,3- ++ (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 70 N-(3,5-dimethyl-4-(5-methylthiophen-2-yl)phenyl)-7- ++ + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 71 N-(4-cyclohexylphenyl)-7-fluoro-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 72 N-(2-chloro-2-methoxy-[1,1-biphenyl]-4-yl)-7-methyl-2,3- + + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 73 N-(2,6-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 74 N-(2,6-dimethyl-[1,1-biphenyl]-4-yl)-7-fluoro-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 75 N-(4-bromo-3-chlorophenyl)-7-methyl-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 76 N-(4-isopropylphenyl)-7-methyl-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 77 N-(2,2-dichloro-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 78 N-(2-chloro-2-(hydroxymethyl)-[1,1-biphenyl]-4-yl)-7- + + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 79 N-(2,3-dihydro-1H-inden-5-yl)-7-methyl-2,3-dioxo-1,2,3,4- + ++ tetrahydroquinoxaline-6-sulfonamide 80 7-chloro-N-(3,5-dimethyl-4-(thiophen-3-yl)phenyl)-2,3- + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 81 N-(2-methoxy-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 82 N-(3-chloro-4-(thiophen-3-yl)phenyl)-7-fluoro-2,3-dioxo- + (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 83 N-(4-(tert-butyl)phenyl)-7-methyl-2,3-dioxo-1,2,3,4- + ++ tetrahydroquinoxaline-6-sulfonamide 84 N-(3,5-dimethyl-4-(5-methylfuran-2-yl)phenyl)-7-methyl- + + 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 85 7-chloro-N-(4-cyclopropylphenyl)-2,3-dioxo-1,2,3,4- + ++ tetrahydroquinoxaline-6-sulfonamide 86 N-(4-cyclohexylphenyl)-7-methyl-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 87 7-fluoro-2,3-dioxo-N-(4-propylphenyl)-1,2,3,4- + ++ tetrahydroquinoxaline-6-sulfonamide 88 7-chloro-N-(4-(furan-3-yl)-3-methylphenyl)-2,3-dioxo- ++ + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 89 7-methyl-N-(2-methyl-[1,1-biphenyl]-4-yl)-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 90 N-(2-chloro-2-methyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3- + + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 91 7-methyl-N-(3-methyl-4-(trifluoromethyl)phenyl)-2,3- + + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 92 N-(4-ethylphenyl)-7-methyl-2,3-dioxo-1,2,3,4- +++ +++ tetrahydroquinoxaline-6-sulfonamide 93 7-chloro-2,3-dioxo-N-(4-(trifluoromethyl)phenyl)-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 94 7-chloro-N-(3-chloro-4-(pyridin-4-yl)phenyl)-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 95 7-fluoro-N-(naphthalen-2-yl)-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 96 7-bromo-N-(4-cyclopropylphenyl)-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 97 N-(4-bromophenyl)-7-methyl-2,3-dioxo-1,2,3,4- + ++ tetrahydroquinoxaline-6-sulfonamide 98 N-([1,1-biphenyl]-4-yl)-7-chloro-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 99 N-(3-chloro-4-(pyridin-3-yl)phenyl)-7-fluoro-2,3-dioxo- + (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 100 N-(3-chloro-4-(thiophen-3-yl)phenyl)-7-isopropyl-2,3- + (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 101 7-fluoro-N-(4-isopropylphenyl)-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 102 N-(2-methoxy-2,6-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl- + ++ 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 103 N-(2,2-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 104 N-(2-chloro-2,6-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl- + + 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 105 7-chloro-N-(2,3-dichloro-2,4-difluoro-[1,1-biphenyl]-4- + + yl)-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 106 7-chloro-N-(2,6-dimethyl-[1,1-biphenyl]-4-yl)-2,3-dioxo- + ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 107 N-(4-(furan-3-yl)-3,5-dimethylphenyl)-7-methyl-2,3-dioxo- + ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 108 N-(2-chloro-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 109 N-(2-chloro-3-(dimethylamino)-[1,1-biphenyl]-4-yl)-7- + + isopropyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 110 N-(4-cyclopropyl-2-methylphenyl)-7-methyl-2,3-dioxo- + ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 111 N-(4-ethoxyphenyl)-7-methyl-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 112 7-methyl-N-(3-methyl-[1,1-biphenyl]-4-yl)-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 113 N-(2-ethyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 114 N-(2-methoxy-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 115 7-methyl-N-(4-methyl-[1,1-biphenyl]-4-yl)-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 116 N-(2,6-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 117 N-(4-isopropyl-3-methylphenyl)-7-methyl-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 118 N-(2,4-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 119 N-(2-(dimethylamino)-[1,1-biphenyl]-4-yl)-7-methyl-2,3- + + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 120 ethyl 4-((7-methyl-2,3-dioxo-1,2,3,4- + (+) tetrahydroquinoxaline)-6-sulfonamido)-[1,1-biphenyl]-2- carboxylate 121 N-(4-bromo-3-methoxyphenyl)-7-methyl-2,3-dioxo-1,2,3,4- + (+) tetrahydroquinoxaline-6-sulfonamide 122 N-(4-bromo-3,5-dimethylphenyl)-7-chloro-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 123 N-(2-acetyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3-dioxo- + (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 124 N-(2-methoxy-2-methyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3- + + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 125 7-methyl-2,3-dioxo-N-(2,2,6-trimethyl-[1,1-biphenyl]-4- + (+) yl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 126 4-((7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline)-6- (+) + sulfonamido)-[1,1-biphenyl]-2-carboxamide 127 7-methyl-2,3-dioxo-N-(4-(pyridin-4-yl)phenyl)-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 128 N-(3-bromo-4-morpholinophenyl)-7-methyl-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 129 N-(4-cyanophenyl)-7-methyl-2,3-dioxo-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 130 N-(4-ethynylphenyl)-7-methyl-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 131 N-(3,5-dimethyl-4-(pyridin-4-yl)phenyl)-7-methyl-2,3- + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 132 N-(3,5-dimethyl-4-(3-methylthiophen-2-yl)phenyl)-7- + + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 133 N-(4-(dimethylamino)phenyl)-7-methyl-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 134 N-(2-ethyl-2,6-dimethyl-[1,1-biphenyl]-4-yl)-7-methyl-2,3- + ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 135 N-(3,5-dimethyl-4-(1H-pyrrol-3-yl)phenyl)-7-methyl-2,3- + + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 136 N-(2-chloro-2-(dimethylamino)-[1,1-biphenyl]-4-yl)-7- + + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 137 7-methyl-2,3-dioxo-N-(4-(pyrrolidin-1-yl)phenyl)-1,2,3,4- + ++ tetrahydroquinoxaline-6-sulfonamide 138 ethyl 2-chloro-4-((7-methyl-2,3-dioxo-1,2,3,4- (+) (+) tetrahydroquinoxaline)-6-sulfonamido)-[1,1-biphenyl]-2- carboxylate 139 N-(2-chloro-2-(trifluoromethyl)-[1,1-biphenyl]-4-yl)-7- + (+) methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 140 N-(3-chloro-4-(2-methylpyridin-4-yl)phenyl)-7-methyl-2,3- + + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 141 N-(4-bromo-3-methylphenyl)-7-chloro-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 142 7-chloro-N-(4-isopropylphenyl)-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 143 7-chloro-N-(3-chloro-4-(trifluoromethyl)phenyl)-2,3-dioxo- + (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 144 N-(4-bromo-3-chlorophenyl)-7-chloro-2,3-dioxo-1,2,3,4- + (+) tetrahydroquinoxaline-6-sulfonamide 145 N-(4-bromo-3,5-dimethylphenyl)-7-chloro-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 146 7-chloro-N-(3-chloro-4-(5-methylfuran-2-yl)phenyl)-2,3- + (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 147 7-fluoro-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 148 N-(4-bromo-3-chlorophenyl)-7-fluoro-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 149 N-(4-bromo-3-chlorophenyl)-7-ethyl-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 150 N-(3-chloro-4-(pyridin-4-yl)phenyl)-7-fluoro-2,3-dioxo- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 151 7-isopropyl-2,3-dioxo-N-(4-propylphenyl)-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 152 7-isopropyl-2,3-dioxo-N-(4-(trifluoromethyl)phenyl)- + ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 153 N-(4-cyclopropylphenyl)-7-isopropyl-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 154 N-(4-bromo-3-chlorophenyl)-7-isopropyl-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 155 7-chloro-N-(3-methyl-4-(pyridin-4-yl)phenyl)-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 156 7-chloro-N-(4-(furan-3-yl)-3,5-dimethylphenyl)-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 157 7-chloro-N-(3,5-dimethyl-4-(pyridin-4-yl)phenyl)-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 158 N-(3-chloro-4-(5-methylfuran-2-yl)phenyl)-7-fluoro-2,3- + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 159 N-(3-chloro-4-(pyridin-4-yl)phenyl)-7-isopropyl-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 160 7-fluoro-2,3-dioxo-N-(4-(trifluoromethyl)phenyl)-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 161 N-(3-chloro-4-(furan-3-yl)phenyl)-7-isopropyl-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 162 N-(4-bromo-3,5-dimethylphenyl)-7-fluoro-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 163 N-(4-bromo-3-methylphenyl)-7-fluoro-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 164 7-fluoro-2,3-dioxo-N-(5,6,7,8-tetrahydronaphthalen-2-yl)- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 165 N-(3-chloro-4-(trifluoromethyl)phenyl)-7-fluoro-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 166 7-fluoro-N-(4-(furan-3-yl)-3,5-dimethylphenyl)-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 167 N-(3,5-dimethyl-4-(pyridin-4-yl)phenyl)-7-fluoro-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 168 7-fluoro-N-(4-(furan-3-yl)-3-methylphenyl)-2,3-dioxo- + (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 169 7-fluoro-N-(3-methyl-4-(pyridin-4-yl)phenyl)-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 170 7-chloro-N-(4-cyclohexylphenyl)-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 171 N-(4-bromo-3-methylphenyl)-7-methyl-2,3-dioxo-1,2,3,4- + ++ tetrahydroquinoxaline-6-sulfonamide 172 7-chloro-N-(naphthalen-2-yl)-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 173 N-(4-(tert-butyl)phenyl)-7-chloro-2,3-dioxo-1,2,3,4- + ++ tetrahydroquinoxaline-6-sulfonamide 174 7-chloro-2,3-dioxo-N-(5,6,7,8-tetrahydronaphthalen-2-yl)- + ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 175 7-methyl-2,3-dioxo-N-(2,3,6-trimethyl-[1,1-biphenyl]-4- + + yl)-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 176 N-(2-chloro-[1,1-biphenyl]-4-yl)-7-isopropyl-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 177 N-(4-chlorophenyl)-7-methyl-2,3-dioxo-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 178 N-(2,3-dichloro-[1,1-biphenyl]-4-yl)-7-isopropyl-2,3-dioxo- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 179 7-methyl-2,3-dioxo-N-(p-tolyl)-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 180 7-methyl-N-(4-morpholinophenyl)-2,3-dioxo-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 181 N-(3-chloro-4-methylphenyl)-7-methyl-2,3-dioxo-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 182 4-((7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline)-6- (+) (+) sulfonamido)-[1,1-biphenyl]-2-carboxylic acid 183 N-(3-chloro-4-fluorophenyl)-7-methyl-2,3-dioxo-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 184 N-(3,5-dimethyl-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-7- (+) methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 185 N-(3,4-dimethylphenyl)-7-methyl-2,3-dioxo-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 186 7-methyl-2,3-dioxo-N-(quinolin-6-yl)-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 187 N-(3,5-dimethyl-4-(1H-pyrazol-4-yl)phenyl)-7-methyl-2,3- (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 188 N-(3,5-dimethyl-4-(1-methyl-1H-pyrazol-5-yl)phenyl)-7- (+) methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 189 N-(3-chloro-4-(5-chloropyridin-3-yl)phenyl)-7-methyl-2,3- ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 190 2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-7- + (trifluoromethyl)-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 191 7-nitro-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 192 2,3-dioxo-7-(trifluoromethoxy)-N-(4- + (trifluoromethoxy)phenyl)-1,2,3,4-tetrahydroquinoxaline- 6-sulfonamide 193 7-methoxy-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 195 7-bromo-N-(4-(tert-butyl)phenyl)-2,3-dioxo-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 196 N-(3-chloro-4-(pyrrolidin-1-yl)phenyl)-7-methyl-2,3-dioxo- ++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 197 N-(2-chloro-4-fluoro-[1,1-biphenyl]-4-yl)-2,3-dioxo-7- (+) (+) (trifluoromethoxy)-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 198 N-(3-chloro-4-(5-methylthiophen-3-yl)phenyl)-7-methyl- 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 199 N-(5-chloro-6-(1H-indol-6-yl)pyridin-3-yl)-7-methyl-2,3- dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 200 N-(3-chloro-4-morpholinophenyl)-7-methyl-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 201 N-(3-chloro-4-(3-methylmorpholino)phenyl)-7-methyl-2,3- + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 202 N-(3-chloro-4-(3,3-dimethylmorpholino)phenyl)-7-methyl- + + 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 203 N-(5-chloro-6-(4-ethynylphenyl)pyridin-3-yl)-7-methyl-2,3- dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 204 N-(3-chloro-4-(2-methylmorpholino)phenyl)-7-methyl-2,3- (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 205 N-(4,5-dichloro-[3,3-bipyridin]-6-yl)-7-methyl-2,3-dioxo- 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 206 N-(3-(azetidin-1-yl)-2-chloro-[1,1-biphenyl]-4-yl)-7- +++ ++ methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 207 7-methyl-2,3-dioxo-N-(1-phenyl-1H-pyrazol-4-yl)-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 208 N-(3-chloro-4-(1,4-oxazepan-4-yl)phenyl)-7-methyl-2,3- (+) dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 209 N-(2-chloro-4-cyano-3-methoxy-[1,1-biphenyl]-4-yl)-7- methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 210 N-(4-chloro-5-(3-chlorophenyl)pyridin-2-yl)-7-methyl-2,3- ++ + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 211 N-(4-chloro-5-(3-chloro-4-fluorophenyl)pyridin-2-yl)-7- + + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 212 N-(4-chloro-5-(4-fluorophenyl)pyridin-2-yl)-7-methyl-2,3- ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 213 N-(5-chloro-6-(3-chlorophenyl)pyridin-3-yl)-7-methyl-2,3- + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 214 N-(5-chloro-6-(3-chloro-4-fluorophenyl)pyridin-3-yl)-7- + methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 215 N-(5-chloro-6-(4-fluorophenyl)pyridin-3-yl)-7-methyl-2,3- ++ dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 216 7-cyano-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)-1,2,3,4- + + tetrahydroquinoxaline-6-sulfonamide 217 7-(methyl-d3)-2,3-dioxo-N-(4-(trifluoromethoxy)phenyl)- +++ +++ 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 218 7-(difluoromethyl)-2,3-dioxo-N-(4- + + (trifluoromethoxy)phenyl)-1,2,3,4-tetrahydroquinoxaline- 6-sulfonamide 219 N-(2-chloro-3,5-difluoro-4-methoxy-[1,1-biphenyl]-4-yl)- 7-methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide 220 N-(2-chloro-4-cyclopropyl-[1,1-biphenyl]-4-yl)-7-methyl- 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 221 7-(dimethylamino)-2,3-dioxo-N-(4- ++ (trifluoromethoxy)phenyl)-1,2,3,4-tetrahydroquinoxaline- 6-sulfonamide 222 7-methyl-2,3-dioxo-N-(5-(trifluoromethoxy)pyridin-2-yl)- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 223 7-methyl-2,3-dioxo-N-(6-(trifluoromethoxy)pyridin-3-yl)- + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 224 7-methyl-2,3-dioxo-N-(6-phenylpyridin-3-yl)-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 225 N-(2,4-dichloro-3-methoxy-[1,1-biphenyl]-4-yl)-7-methyl- 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 226 N-(5-bromo-4-chloropyridin-2-yl)-7-methyl-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 227 N-(3-chloro-4-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin- 7-yl)phenyl)-7-methyl-2,3-dioxo-1,2,3,4- tetrahydroquinoxaline-6-sulfonamide 228 7-methyl-N-(1-methyl-1H-indol-5-yl)-2,3-dioxo-1,2,3,4- (+) tetrahydroquinoxaline-6-sulfonamide 229 N-(3-chloro-4-(isoquinolin-7-yl)phenyl)-7-methyl-2,3-dioxo- 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 230 7-methyl-2,3-dioxo-N-(3-phenylbicyclo[1.1.1]pentan-1-yl)- + + 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 231 7-methyl-2,3-dioxo-N-(quinolin-7-yl)-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 232 N-(3-chloro-4-(2-methylquinolin-6-yl)phenyl)-7-methyl-2,3- dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 233 N-(3-chloro-4-(isoquinolin-6-yl)phenyl)-7-methyl-2,3-dioxo- 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 234 7-methyl-N-(2-methylbenzo[d]thiazol-5-yl)-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 235 N-(3-chloro-4-(quinolin-6-yl)phenyl)-7-methyl-2,3-dioxo- 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 236 N-(6-bromo-5-chloropyridin-3-yl)-7-methyl-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 237 2-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-2H- + [1,4,5]oxathiazepino[2,3-g]quinoxaline-8,9(7H,10H)-dione 1,1-dioxide 238 N-(benzo[d]thiazol-2-yl)-7-methyl-2,3-dioxo-1,2,3,4- + tetrahydroquinoxaline-6-sulfonamide 239 7-methyl-N-(2-methylbenzo[d]thiazol-6-yl)-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 240 7-methyl-N-(4-methyl-5-phenylthiazol-2-yl)-2,3-dioxo- (+) 1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 241 N-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-7-methyl-2,3- + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 242 N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-7-methyl-2,3- + dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 243 (R)-N-(3-chloro-4-(3-methylmorpholino)phenyl)-7-methyl- (+) + 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonamide 244 N-[3-bromo-4-(4-fluorophenyl)phenyl]-7-methyl-2,3-dioxo- +++ ++ 1,4-dihydroquinoxaline-6-sulfonamide 245 3-[2-chloro-4-[(7-methyl-2,3-dioxo-1,4-dihydroquinoxalin- +++ ++ 6-yl)sulfonylamino]phenyl] benzamide 246 N-[3-chloro-4-(4-methoxyphenyl)phenyl]-7-methyl-2,3- +++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 247 N-[4-(1,3-benzodioxol-5-yl)-3-chloro-phenyl]-7-methyl-2,3- +++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 248 N-[3-chloro-4-(3,5-dimethylphenyl)phenyl]-7-methyl-2,3- + + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 249 N-[4-(3-acetylphenyl)-3-chloro-phenyl]-7-methyl-2,3-dioxo- +++ + 1,4-dihydroquinoxaline-6-sulfonamide 250 N-[4-(4-fluorophenyl)-3-morpholino-phenyl]-7-methyl-2,3- + (+) dioxo-1,4-dihydroquinoxaline-6-sulfonamide 251 N-[3-ethynyl-4-(4-ethynylphenyl)phenyl]-7-methyl-2,3- +++ +++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 252 N-(3-ethynyl-4-phenyl-phenyl)-7-methyl-2,3-dioxo-1,4- +++ ++ dihydroquinoxaline-6-sulfonamide 253 N-[4-(4-cyanophenyl)-3-ethynyl-phenyl]-7-methyl-2,3- +++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 254 N-[3-chloro-4-(6-cyano-3-pyridyl)phenyl]-7-methyl-2,3- + + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 255 N-[3-(dimethylamino)-4-(4-fluorophenyl)phenyl]-7-methyl- + + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 256 N-[4-(1H-benzotriazol-5-yl)-3-chloro-phenyl]-7-methyl-2,3- +++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 257 N-[3-chloro-4-(3,4-dichlorophenyl)phenyl]-7-methyl-2,3- +++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 258 N-[3-chloro-4-(3,5-dimethoxyphenyl)phenyl]-7-methyl-2,3- + + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 259 N-[3-chloro-4-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-7- +++ + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 260 N-[3-chloro-4-(2-methoxypyrimidin-5-yl)phenyl]-7-methyl- + + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 261 N-[3-chloro-4-(2-fluoro-4-methoxy-phenyl)phenyl]-7- +++ ++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 262 N-[3-chloro-4-(2-fluoro-4-methylsulfonyl-phenyl)phenyl]-7- (+) (+) methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 263 N-[3-chloro-4-(1,2,4-triazol-1-yl)phenyl]-7-methyl-2,3- (+) + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 264 N-[3-chloro-4-(triazol-1-yl)phenyl]-7-methyl-2,3-dioxo-1,4- + + dihydroquinoxaline-6-sulfonamide 265 7-methyl-2,3-dioxo-N-[4-(1,2,4-triazol-1-yl)phenyl]-1,4- (+) (+) dihydroquinoxaline-6-sulfonamide 266 N-[3-chloro-4-(3,4-dimethylphenyl)phenyl]-7-methyl-2,3- + + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 267 N-[3-chloro-4-[4-(trideuteriomethoxy)phenyl]phenyl]-7- +++ ++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 268 N-[3-chloro-4-[4-(cyclopropoxy)phenyl]phenyl]-7-methyl- ++ + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 269 N-[3-chloro-4-(2-methyl-1,3-benzoxazol-6-yl)phenyl]-7- +++ +++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 270 N-[3-chloro-4-(1H-indol-5-yl)phenyl]-7-methyl-2,3-dioxo- + ++ 1,4-dihydroquinoxaline-6-sulfonamide 271 N-[3-chloro-4-(1H-indol-6-yl)phenyl]-7-methyl-2,3-dioxo- +++ +++ 1,4-dihydroquinoxaline-6-sulfonamide 272 N-[3-chloro-4-(2-methyl-1,3-benzoxazol-5-yl)phenyl]-7- +++ +++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 273 N-[3-chloro-4-(1H-indazol-5-yl)phenyl]-7-methyl-2,3-dioxo- ++ + 1,4-dihydroquinoxaline-6-sulfonamide 274 N-[3-chloro-4-(cyclohexen-1-yl)phenyl]-7-methyl-2,3- ++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 275 N-[3-chloro-4-[6-(trifluoromethyl)-3-pyridyl]phenyl]-7- + (+) methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 276 2,3-dioxo-7-(2,2,2-trifluoroethoxy)-N-[4- ++ +++ (trifluoromethoxy)phenyl]-1,4-dihydroquinoxaline-6- sulfonamide 277 N-[3-chloro-4-[4-(trifluoromethoxy)phenyl]phenyl]-7- + + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 278 7-ethoxy-2,3-dioxo-N-[4-(trifluoromethoxy)phenyl]-1,4- + +++ dihydroquinoxaline-6-sulfonamide 279 N-[5-chloro-6-(5-chloro-3-pyridyl)-3-pyridyl]-7-methyl-2,3- + + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 280 N-[3-chloro-4-(2-oxo-1H-pyridin-4-yl)phenyl]-7-methyl-2,3- (+) + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 281 7-(2-hydroxyethylamino)-2,3-dioxo-N-[4- +++ +++ (trifluoromethoxy)phenyl]-1,4-dihydroquinoxaline-6- sulfonamide 282 N-[3-chloro-4-[2-fluoro-5-(hydroxymethyl)phenyl]phenyl]- ++ + 7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 283 N-[3-chloro-4-(1-methylbenzimidazol-5-yl)phenyl]-7- + + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 284 N-(3-chloro-4-cyclohexyl-phenyl)-7-methyl-2,3-dioxo-1,4- ++ + dihydroquinoxaline-6-sulfonamide 285 N-(3-chloro-4-imidazol-1-yl-phenyl)-7-methyl-2,3-dioxo- + + 1,4-dihydroquinoxaline-6-sulfonamide 286 N-[3-chloro-4-(3-chloro-4-methyl-phenyl)phenyl]-7-methyl- ++ + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 287 N-[3-chloro-4-(2,2-difluoro-1,3-benzodioxol-5-yl)phenyl]-7- ++ ++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 288 N-[3-chloro-4-[4-(dimethylamino)phenyl]phenyl]-7-methyl- + (+) 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 289 N-[3-chloro-4-(3-cyano-4-methoxy-phenyl)phenyl]-7- ++ + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 290 N-[3-chloro-4-(5-cyano-3-thienyl)phenyl]-7-methyl-2,3- +++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 291 N-[3-chloro-4-(6-isopropoxy-3-pyridyl)phenyl]-7-methyl- + + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 292 N-(4-imidazol-1-ylphenyl)-7-methyl-2,3-dioxo-1,4- (+) (+) dihydroquinoxaline-6-sulfonamide 293 N-[3-chloro-4-[(E)-2-ethoxyvinyl]phenyl]-7-methyl-2,3- + (+) dioxo-1,4-dihydroquinoxaline-6-sulfonamide 294 N-[3-chloro-4-(2-oxo-1,3-dihydrobenzimidazol-5- + + yl)phenyl]-7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6- sulfonamide 295 N-[3-chloro-4-(2,5-difluorophenyl)phenyl]-7-methyl-2,3- ++ + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 296 N-[3-chloro-4-(2-methylprop-1-enyl)phenyl]-7-methyl-2,3- ++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 297 N-[4-(3,6-dihydro-2H-pyran-4-yl)phenyl]-7-methyl-2,3- + + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 298 N-[3-bromo-4-(4-cyanophenyl)phenyl]-7-methyl-2,3-dioxo- +++ ++ 1,4-dihydroquinoxaline-6-sulfonamide 299 N-[3-bromo-4-(cyclohexen-1-yl)phenyl]-7-methyl-2,3- ++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 300 N-[3-ethynyl-4-(3-fluoro-4-methoxy-phenyl)phenyl]-7- +++ +++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 301 N-[3-ethynyl-4-(1H-indol-6-yl)phenyl]-7-methyl-2,3-dioxo- +++ +++ 1,4-dihydroquinoxaline-6-sulfonamide 302 N-[3-bromo-4-(3-fluoro-4-methoxy-phenyl)phenyl]-7- +++ +++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 303 N-[5-chloro-6-(3-fluoro-4-methoxy-phenyl)-3-pyridyl]-7- + + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 304 7-methyl-2,3-dioxo-N-(4-tetrahydropyran-4-ylphenyl)-1,4- (+) + dihydroquinoxaline-6-sulfonamide 305 N-[5-chloro-6-(4-cyanophenyl)-3-pyridyl]-7-methyl-2,3- + ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 306 N-(3-bromo-4-cyclohexyl-phenyl)-7-methyl-2,3-dioxo-1,4- ++ + dihydroquinoxaline-6-sulfonamide 307 N-[3-chloro-4-(2,3,4-trifluorophenyl)phenyl]-7-methyl-2,3- ++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 308 N-[3-chloro-4-(2,6-difluorophenyl)phenyl]-7-methyl-2,3- ++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 309 N-[3-chloro-4-(3,5-difluorophenyl)phenyl]-7-methyl-2,3- +++ + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 310 N-[4-(3-bromophenyl)-3-chloro-phenyl]-7-methyl-2,3- +++ + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 311 N-[4-(3-aminophenyl)-3-chloro-phenyl]-7-methyl-2,3- ++ +++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 312 N-[3-chloro-4-(3-dimethylphosphorylphenyl)phenyl]-7- + + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 313 N-[3-chloro-4-(3-methylsulfonylphenyl)phenyl]-7-methyl- + + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 314 4-[2-chloro-4-[(7-methyl-2,3-dioxo-1,4-dihydroquinoxalin- + + 6-yl)sulfonylamino]phenyl]benzamide 315 N-[3-chloro-4-(3,5-dichlorophenyl)phenyl]-7-methyl-2,3- + (+) dioxo-1,4-dihydroquinoxaline-6-sulfonamide 316 N-[3-chloro-4-[3-(trifluoromethyl)phenyl]phenyl]-7-methyl- ++ (+) 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 317 N-[3-chloro-4-[4-(trifluoromethyl)phenyl]phenyl]-7-methyl- + (+) 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 318 N-[3-chloro-4-(3-cyanophenyl)phenyl]-7-methyl-2,3-dioxo- ++ + 1,4-dihydroquinoxaline-6-sulfonamide 319 N-[3-chloro-4-(4-ethoxyphenyl)phenyl]-7-methyl-2,3- ++ + dioxo-1,4-dihydroquinoxaline-6-sulfonamide 320 N-[3-chloro-4-(3-fluoro-4-methoxy-phenyl)phenyl]-7- +++ +++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 321 N-(4-benzyl-3-chloro-phenyl)-7-methyl-2,3-dioxo-1,4- + + dihydroquinoxaline-6-sulfonamide 322 N-[3-bromo-4-(trifluoromethoxy)phenyl]-7-methyl-2,3- ++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 323 7-methyl-N-[3-methyl-4-(trifluoromethoxy)phenyl]-2,3- ++ +++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 324 N-[3-chloro-4-(trifluoromethoxy)phenyl]-7-methyl-2,3- ++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 325 N-[4-iodo-3-(trifluoromethyl)phenyl]-7-methyl-2,3-dioxo- + (+) 1,4-dihydroquinoxaline-6-sulfonamide 326 N-[4-(4-fluorophenyl)-3-(trifluoromethyl)phenyl]-7-methyl- +++ ++ 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 327 N-[4-(4-fluorophenyl)-3-(trifluoromethoxy)phenyl]-7- + + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 328 N-(3-chloro-4-imidazo[1,2-a]pyridin-6-yl-phenyl)-7-methyl- + + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 329 N-[3-chloro-4-(4-methyl-2,3-dihydro-1,4-benzoxazin-7- + (+) yl)phenyl]-7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6- sulfonamide 330 N-[3-chloro-4-[3-(4-methylpiperazin-1-yl)phenyl]phenyl]-7- + + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 331 N-[3-chloro-4-[3-[2- + + (dimethylamino)ethoxy]phenyl]phenyl]-7-methyl-2,3- dioxo-1,4-dihydroquinoxaline-6-sulfonamide 332 3-[4-[2-chloro-4-[(7-methyl-2,3-dioxo-1,4- + + dihydroquinoxalin-6-yl)sulfonylamino]phenyl]phenyl]-1,1- dimethyl-urea 333 N-[3-chloro-4-[3-(hydroxymethyl)phenyl]phenyl]-7-methyl- ++ + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 334 N-[3-chloro-4-(1-oxo-3,4-dihydro-2H-isoquinolin-6- + (+) yl)phenyl]-7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6- sulfonamide 335 N-[3-chloro-4-[3-(dimethylsulfamoyl)phenyl]phenyl]-7- + (+) methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 336 N-(3-chloro-4-imidazo[1,2-a]pyridin-7-yl-phenyl)-7-methyl- ++ + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 337 N-[3-chloro-4-([1,2,4]triazolo[1,5-a]pyridin-7-yl)phenyl]-7- ++ ++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 338 N-[3-chloro-4-(2-methylimidazo[1,2-a]pyridin-7-yl)phenyl]- +++ ++ 7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 339 N-[3-chloro-4-[3-(trifluoromethoxy)phenyl]phenyl]-7- ++ + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 340 N-[3-chloro-4-(1-methylindol-3-yl)phenyl]-7-methyl-2,3- + (+) dioxo-1,4-dihydroquinoxaline-6-sulfonamide 341 N-[3-chloro-4-(1-methylindolin-5-yl)phenyl]-7-methyl-2,3- + (+) dioxo-1,4-dihydroquinoxaline-6-sulfonamide 342 N-[4-[3-(aminomethyl)phenyl]-3-chloro-phenyl]-7-methyl- (+) + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 343 N-[3-chloro-4-(1,2,3,4-tetrahydroquinolin-6-yl)phenyl]-7- +++ + methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 344 N-[3-chloro-4-[1-(2-methoxyethyl)pyrazol-4-yl]phenyl]-7- (+) (+) methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 345 N-[4-(3-fluoro-4-methoxy-phenyl)-3- +++ +++ (trifluoromethyl)phenyl]-7-methyl-2,3-dioxo-1,4- dihydroquinoxaline-6-sulfonamide 346 N-[2-hydroxy-5-[4-[(7-methyl-2,3-dioxo-1,4- ++ + dihydroquinoxalin-6-yl)sulfonylamino]-2- (trifluoromethyl)phenyl]phenyl]acetamide 347 N-[4-indolin-6-yl-3-(trifluoromethyl)phenyl]-7-methyl-2,3- +++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 348 N-[4-(4-cyanophenyl)-3-(trifluoromethyl)phenyl]-7-methyl- +++ + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 349 N-[3-chloro-4-(2-methyl-1H-indol-6-yl)phenyl]-7-methyl- +++ +++ 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 350 N-[3-chloro-4-(2-oxoindolin-6-yl)phenyl]-7-methyl-2,3- ++ ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 351 N-[3-chloro-4-(7-quinolyl)phenyl]-7-methyl-2,3-dioxo-1,4- +++ + dihydroquinoxaline-6-sulfonamide 352 N-[3-chloro-4-(3-methyl-1H-indol-6-yl)phenyl]-7-methyl- + + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 353 N-[3-chloro-4-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)phenyl]- ++ + 7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 354 N-[3-chloro-4-(4-methyl-2,3-dihydro-1,4-benzoxazin-6- ++ + yl)phenyl]-7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6- sulfonamide 355 N-[3-chloro-4-(3-oxo-4H-1,4-benzoxazin-6-yl)phenyl]-7- +++ +++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 356 N-[3-chloro-4-(4-methyl-3-oxo-1,4-benzoxazin-6- +++ ++ yl)phenyl]-7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6- sulfonamide 357 N-[3-chloro-4-(8-fluoro-3,4-dihydro-2H-1,4-benzoxazin-6- +++ + yl)phenyl]-7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6- sulfonamide 358 N-[3-chloro-4-(6-oxo-1H-pyridin-3-yl)phenyl]-7-methyl-2,3- + ++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 359 N-[4-(3H-benzimidazol-5-yl)-3-chloro-phenyl]-7-methyl- + ++ 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 360 N-[3-chloro-4-[4-cyano-3-(dimethylamino)phenyl]phenyl]- ++ + 7-methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 361 N-[3-chloro-4-(2-methyl-3H-benzimidazol-5-yl)phenyl]-7- ++ +++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 362 N-(4-cyclobutylphenyl)-7-methyl-2,3-dioxo-1,4- + ++ dihydroquinoxaline-6-sulfonamide 363 3-fluoro-5-[4-[(7-methyl-2,3-dioxo-1,4-dihydroquinoxalin- ++ ++ 6-yl)sulfonylamino]-2-(trifluoromethyl)phenyl]benzamide 364 7-methyl-N-[4-(2-methyl-1H-indol-6-yl)-3- +++ +++ (trifluoromethyl)phenyl]-2,3-dioxo-1,4-dihydroquinoxaline- 6-sulfonamide 365 7-methyl-2,3-dioxo-N-[4-(7-quinolyl)-3- +++ + (trifluoromethyl)phenyl]-1,4-dihydroquinoxaline-6- sulfonamide 366 N-[4-(3-hydroxyphenyl)-3-(trifluoromethyl)phenyl]-7- +++ ++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 367 7-methyl-2,3-dioxo-N-[4-(3-oxo-4H-1,4-benzoxazin-6-yl)-3- +++ ++ (trifluoromethyl)phenyl]-1,4-dihydroquinoxaline-6- sulfonamide 368 2-fluoro-5-[4-[(7-methyl-2,3-dioxo-1,4-dihydroquinoxalin- ++ + 6-yl)sulfonylamino]-2-(trifluoromethyl)phenyl]benzamide 369 N-[4-(1H-indol-6-yl)-3-(trifluoromethyl)phenyl]-7-methyl- +++ ++ 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 370 N-[3-chloro-4-(1H-indazol-6-yl)phenyl]-7-methyl-2,3-dioxo- +++ +++ 1,4-dihydroquinoxaline-6-sulfonamide 371 N-[3-chloro-4-(3-chloro-4-methoxy-phenyl)phenyl]-7- methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 372 N-[3-chloro-4-(4-methyl-2-thienyl)phenyl]-7-methyl-2,3- dioxo-1,4-dihydroquinoxaline-6-sulfonamide 373 N-[3-ethynyl-4-(2-methyl-1,3-benzoxazol-5-yl)phenyl]-7- +++ +++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 374 N-[3-bromo-4-(1H-indol-6-yl)phenyl]-7-methyl-2,3-dioxo- +++ +++ 1,4-dihydroquinoxaline-6-sulfonamide 375 N-[5-chloro-6-(2-methyl-1,3-benzoxazol-5-yl)-3-pyridyl]-7- ++ ++ methyl-2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 376 N-[3-chloro-4-(4-cyanophenyl)phenyl]-7-methyl-2,3-dioxo- +++ ++ 1,4-dihydroquinoxaline-6-sulfonamide 377 N-[3-cyano-4-(4-fluorophenyl)phenyl]-7-methyl-2,3-dioxo- + + 1,4-dihydroquinoxaline-6-sulfonamide 378 N-[3-ethynyl-4-(4-fluorophenyl)phenyl]-7-methyl-2,3- +++ +++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 379 N-[5-chloro-6-(4-fluorophenyl)-3-pyridyl]-7-cyclopropyl- + + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 380 N-(4-chlorophenyl)-7-methoxy-2,3-dioxo-1,4- (+) + dihydroquinoxaline-6-sulfonamide 381 7-(methylamino)-2,3-dioxo-N-[4- + + (trifluoromethoxy)phenyl]-1,4-dihydroquinoxaline-6- sulfonamide 382 7-(cyclopropoxy)-2,3-dioxo-N-[4- (+) + (trifluoromethoxy)phenyl]-1,4-dihydroquinoxaline-6- sulfonamide 383 N-(4-bromophenyl)-7-methoxy-2,3-dioxo-1,4- (+) + dihydroquinoxaline-6-sulfonamide 384 7-methyl-N-[4-(oxetan-3-yl)phenyl]-2,3-dioxo-1,4- (+) + dihydroquinoxaline-6-sulfonamide 385 N-[5-chloro-6-(triazol-2-yl)-3-pyridyl]-7-methyl-2,3-dioxo- (+) + 1,4-dihydroquinoxaline-6-sulfonamide 386 N-[3-chloro-4-(3-hydroxyphenyl)phenyl]-7-methyl-2,3- +++ +++ dioxo-1,4-dihydroquinoxaline-6-sulfonamide 387 N-[3-chloro-4-(4-fluorophenyl)phenyl]-2,3-dioxo-7- +++ ++ (trideuteriomethyl)-1,4-dihydroquinoxaline-6-sulfonamide 388 N-(1-hydroxy-3H-2,1-benzoxaborol-6-yl)-7-methyl-2,3- + (+) dioxo-1,4-dihydroquinoxaline-6-sulfonamide 389 5-[2-chloro-4-[(7-methyl-2,3-dioxo-1,4-dihydroquinoxalin- +++ ++ 6-yl)sulfonylamino]phenyl]-2-fluoro-benzamide 390 3-[2-chloro-4-[(7-methyl-2,3-dioxo-1,4-dihydroquinoxalin- +++ +++ 6-yl)sulfonylamino]phenyl]-5-fluoro-benzamide 391 N-[4-(difluoromethoxy)phenyl]-7-methoxy-2,3-dioxo-1,4- (+) + dihydroquinoxaline-6-sulfonamide 392 N-[5-chloro-6-(4-fluorophenyl)-3-pyridyl]-2,3-dioxo-7- ++ + (trideuteriomethyl)-1,4-dihydroquinoxaline-6-sulfonamide 393 N-[3-chloro-4-(3-cyano-4-fluoro-phenyl)phenyl]-7-methyl- ++ + 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 394 N-[4-(difluoromethoxy)phenyl]-7-methyl-2,3-dioxo-1,4- + ++ dihydroquinoxaline-6-sulfonamide 395 5-[2-chloro-4-[(7-methyl-2,3-dioxo-1,4-dihydroquinoxalin- (+) 6-yl)sulfonylamino]phenyl]-2-methoxy-benzamide 396 7-methyl-2,3-dioxo-N-[4-(trifluoromethylsulfanyl)phenyl]- + ++ 1,4-dihydroquinoxaline-6-sulfonamide 397 N-[4-(4-fluorophenyl)-3-methylsulfonyl-phenyl]-7-methyl- (+) 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 398 N-[3-chloro-4-(4-methylsulfonylphenyl)phenyl]-7-methyl- (+) (+) 2,3-dioxo-1,4-dihydroquinoxaline-6-sulfonamide 399 7-methoxy-2,3-dioxo-N-[4- (+) + (trifluoromethylsulfanyl)phenyl]-1,4-dihydroquinoxaline-6- sulfonamide 400 7-methoxy-2,3-dioxo-N-[4-(trifluoromethyl)phenyl]-1,4- (+) + dihydroquinoxaline-6-sulfonamide 401 N-(4-ethynyl-2-(trifluoromethyl)-[1,1-biphenyl]-4-yl)-7- methyl-2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6- sulfonamide

[0380] Comparison of compounds of the present invention with compounds of formula (I) wherein R.sup.2 is hydrogen:

TABLE-US-00008 R.sup.2 = H R.sup.2 = CH.sub.3 Ca.sup.2+-Influx/LDH Ca.sup.2+-Influx/LDH Assays EC.sub.50 (M) Assays EC.sub.50 (M) [00469] 0.290/0.241 0.037/0.014 [00470] 0.423/0.080 0.063/0.018 [00471] 1.69/0.346 0.267/0.091

[0381] As can be taken from the above comparison, the presence of group R.sup.2 significantly enhances the activity of the compounds of the present invention against S. aureus. All of the pairs shown above show a significant increase in activity upon addition of a substituent at position R.sup.2.