US 2015/0307461 A1Published application

Antiviral compounds

AssigneeHoffmann-La Roche Inc.

InventorsJoseph A. Bilotta, Zhi Chen, Elbert Chin, Qingjie Ding, Shawn D. Erickson, Stephen D. Gabriel, Klaus G. Klumpp, Han Ma, Eric Mertz, Jean-Marc Plancher, Robert J. Weikert

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Abstract

The present invention discloses compounds of Formula I: wherein the variables in Formula I are defined as described herein. Also disclosed are pharmaceutical compositions containing such compounds and methods for using the compounds of Formula I in the prevention or treatment of HCV infection.

Claims23

Dependent claims

A compound of formula I

wherein:
R1 is H, halo, lower haloalkyl, lower haloalkyl lower alkyl, trifluoromethyl sulfonyl, lower alkyl, alkoxy, nitro, carboxyl, lower alkyl sulfonamido, trifluoromethyl sulfinyl, cycloalkyl, SF5, or —NHNH2;
R2 is H, halo, cyano, nitro, trifluoromethyl sulfonyl, lower halo alkyl, phenyl ethynyl, lower alkyl sulfonyl, lower alkyl amino sulfonyl, lower alkyl amido, amino sulfonyl, sulfonamido, benzyl oxy, cycloalkyl, heterocycloalkyl sulfonyl, aryl carbonyl, lower alkyl urea, lower alkyl ester, phenyl amido, heterocycloalkyl carbonyl, lower alkyl sulfonyl phenyl amido, lower alkyl cyano, cyano lower alkyl, or tetrazolyl lower alkyl;
R3 is H, halo, lower alkyl, lower alkenyl, lower haloalkyl, cyano, lower haloalkyl oxy, cyano cycloalkyl, lower haloalkyl lower alkyl, SF5, or trifluoromethyl sulfanyl;
or R2 and R3 together form an aryl ring system;
R4 is H, lower alkyl, cyano lower alkyl, or phenyl lower alkyl;
R5 is absent, H, lower alkyl, or cycloalkyl;
R6 is H or halo;
R7 is absent, H, loweralkyl carbonyl, or lower haloalkyl phenyl sulfonyl;
with the proviso that when R5 is absent, R7 is not absent;
and
with the proviso that when R7 is absent, R5 is not absent;
or a pharmaceutically acceptable salt thereof.

10 more elements

A compound selected from the group consisting of:

N3-(4-Bromo-3,5-dichloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-benzonitrile;
N3-(3,5-Dichloro-4-iodo-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Trifluoromethanesulfonyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(4-Bromo-3-chloro-5-fluoro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-tert-Butyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-4-trifluoromethanesulfonyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-4-nitro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-4-ethynyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-4-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3,4,5-Trichloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-chloro-benzonitrile;
N3-(4-Chloro-3-nitro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-4-phenylethynyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Bromo-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-tert-butyl-benzonitrile;
N3-(4-Trifluoromethanesulfonyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-Naphthalen-2-yl-1H-[1,2,4]triazole-3,5-diamine;
N3-(3,5-Di-tert-butyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(4-Methanesulfonyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Methanesulfonyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-N-methyl-benzenesulfonamide;
[4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-phenyl]-morpholin-4-yl-methanone;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-N,N-dimethyl-benzamide;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-benzenesulfonamide;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-N,N-dimethyl-benzenesulfonamide;
N3-Methyl-N3-(3,4,5-trichloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3,5-Dichloro-phenyl)-N3-methyl-1H-[1,2,4]triazole-3,5-diamine;
N3-Benzyl-N3-(3,5-dichloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
[(5-Amino-1H-[1,2,4]triazol-3-yl)-(3,5-dichloro-phenyl)-amino]-acetonitrile;
3-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-benzoic acid;
N3-(3-Trifluoromethanesulflnyl-5-trifluoromethylsulfanyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N-[3-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-phenyl]-methanesulfonamide;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-trifluoromethanesulfonyl-benzonitrile;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-cyclopropyl-benzonitrile;
N3-(3-Chloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(4-Benzyloxy-3-chloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3,5-Dichloro-4-methyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine
N3-(3,5-Dichloro-4-cyclopropyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine
N3-(4-Bromo-3-chloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3,5-Dichloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(4-Bromo-3-chloro-5-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-chloro-6-trifluoromethyl-benzonitrile;
N3-[3,5-Dichloro-4-(morpholine-4-sulfonyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;
N5-(4-Bromo-3-fluoro-5-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N5-(4-Bromo-3,5-difluoro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-benzonitrile;
3-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-5-chloro-benzonitrile;
N3-(2,3-Dichloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-5-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(4-Chloro-3-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Trifluoromethoxy-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(2-Fluoro-3-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(2-Fluoro-5-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-[3-(2,2,2-Trifluoro-ethyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Isopropyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
[3-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-phenyl]-phenyl-methanone;
1-[3-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-phenyl]-cyclopropanecarbonitrile;
N3-(3-Chloro-4-fluoro-5-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-5-fluoro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
1-[4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-chloro-phenyl]-3-methyl-urea;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-benzoic acid methyl ester;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-N-phenyl-benzamide;
[4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-phenyl]-pyrrolidin-1-yl-methanone;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-N-(3-methanesulfonyl-phenyl)-benzamide;
N3-(3,5-Dichloro-4-vinyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-2H-[1,2,4]triazol-3-ylamino)-2-fluoro-6-trifluoromethyl-benzonitrile;
N3-(3-Fluoro-5-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-2H-[1,2,4]triazol-3-ylamino)-2,6-difluoro-benzonitrile;
N*3*-(3-pentafluorosulfur-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
1-Methyl-N*5*-(3-pentafluorosulfur-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
Cyclohexyl-N*5*-(3-pentafluorosulfur-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N*3*-(3-Fluoro-5-pentafluorosulfur-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N*5*-(3-Fluoro-5-pentafluorosulfur-phenyl)-1-methyl-1H-[1,2,4]triazole-3,5-diamine;
N*3*-(4-pentafluorosulfur-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-4-methyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N3-(3-Chloro-4-methanesulfonyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-chloro-N,N-dimethyl-benzamide;
N3-[3,5-Dichloro-4-(3,3-dimethyl-but-1-ynyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;
N3-[3-Chloro-4-(3,3-dimethyl-but-1-ynyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;
N*3*-(4-Bromo-3-pentafluorosulfur-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N*3*-(3-Bromo-5-pentafluorosulfur-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
N*3*-(4-Bromo-3-fluoro-5-pentafluorosulfur-phenyl)-1H-[1,2,4]triazole-3,5-diamine;
[4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-chloro-6-trifluoromethyl-phenyl]-acetonitrile;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-pentafluorosulfur-benzonitrile;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-fluoro-6-pentafluorosulfur-benzonitrile;
4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-hydrazino-6-pentafluorosulfur-benzonitrile;
4-(1-Acetyl-5-amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-benzonitrile;
4-[5-Amino-1-(4-trifluoromethyl-benzenesulfonyl)-1H-[1,2,4]triazol-3-ylamino]-2,6-dichloro-benzonitrile;
and
N3-[3-Chloro-4-(1H-tetrazol-5-ylmethyl)-5-trifluoromethyl-phenyl]-1H-[1,2,4]triazole-3,5-diamine.

88 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/792,722Filed 7 Jul 2015
Priority: 6 Jul 2012
Published: 29 Oct 2015
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 249/14
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
A61K 31/4196
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: 1,2,4-Triazoles
A61K 31/5377
1,4-Oxazines, e.g. morpholine: not condensed and containing further heterocyclic rings, e.g. timolol
A61K 38/21
Cytokines; Lymphokines; Interferons: interferons [IFN]

Family

Application61/668,547Us provisional application · filed 6 Jul 2012
Application13/933,468Continuation · filed 2 Jul 2013
Application14/792,722Continuation
US 2014/0010783 A1Published application
US 2015/0307461 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

Facts

Application

14/792,722Filed 7 Jul 2015

Priority

6 Jul 2012

Published

29 Oct 2015

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 249/14
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
A61K 31/4196
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: 1,2,4-Triazoles
A61K 31/5377
1,4-Oxazines, e.g. morpholine: not condensed and containing further heterocyclic rings, e.g. timolol
A61K 38/21
Cytokines; Lymphokines; Interferons: interferons [IFN]