US2014242028A1PendingUtilityA1

Antiviral compounds

Assignee: HOFFMANN LA ROCHEPriority: Jan 23, 2013Filed: Jan 21, 2014Published: Aug 28, 2014
Est. expiryJan 23, 2033(~6.5 yrs left)· nominal 20-yr term from priority
A61P 31/14A61P 1/16A61K 31/4439C07D 249/14C07D 401/12A61K 31/4196A61K 45/06
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Claims

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.

Claims

exact text as granted — not AI-modified
1 . A compound of formula I 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is H or lower alkyl; 
         each R 2  is independently halo or lower haloalkyl; 
         n is 0, 1, or 2; 
         R 3  is lower haloalkyl, cyano, lower alkoxy, C(═O)OCH 3 , or S(═O) 2 CH 3 ; 
         p is 0, or 1; 
         X 1  is S, S(═O) 2 , O, S(═O), NH, or OCH 2 ; and 
         X 2  is CH or N; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound of  claim 1 , wherein X 2  is CH and R 1  is H. 
     
     
         3 . The compound of  claim 2 , wherein X 1  is S or 0. 
     
     
         4 . The compound of  claim 2 , wherein X 1  is S(═O) 2  or S(═O). 
     
     
         5 . The compound of any one of  claim 1 , wherein n is 1. 
     
     
         6 . The compound of any one of  claim 1 , wherein n is 2. 
     
     
         7 . The compound of  claim 5 , wherein R 1  is Cl. 
     
     
         8 . The compound of  claim 6 , wherein both R 1  are Cl. 
     
     
         9 . The compound of any one of  claim 1 , wherein p is 0. 
     
     
         10 . The compound of any one of  claim 1 , wherein p is 1. 
     
     
         11 . The compound of  claim 10 , wherein R 3  is or S(═O) 2 CH 3 , cyano, or CF 3 . 
     
     
         12 . A compound selected from the group consisting of:
 N5-(3-Fluoro-4-phenylsulfanyl-5-trifluoromethyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N3-(3-Chloro-4-phenylamine-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N3-(3-Chloro-4-phenoxy-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N3(3,5-Dichloro-4-phenylsulfanyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N3(4-Benzenesulfinyl-3,5-dichloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N3(4-Benzenesulfinyl-3,5-dichloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N3-[3,5-Dichloro-4-(4-trifluoromethyl-phenylsulfanyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N3-[3,5-Dichloro-4-(4-trifluoromethyl-benzenesulfinyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N3-[3,5-Dichloro-4-(4-trifluoromethyl-benzenesulfinyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N 3 -[3,5-Dichloro-4-(2-trifluoromethyl-phenylsulfanyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N 3 -[3,5-Dichloro-4-(3-trifluoromethyl-benzenesulfinyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   4-[4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-phenylsulfanyl]-benzonitrile;   4-[4(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-benzenesulfinyl]-benzonitrile;   4-[4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2,6-dichloro-benzenesulfonyl]-benzonitrile;   4-[4-(5-Amino-1H-[1,2,4]triazol-3-ylamino)-2-chloro-6-trifluoromethyl-phenylsulfanyl]-benzoic acid methyl ester;   N 3 -[3,5-Dichloro-4-(4-methoxy-phenylsulfanyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N 3 -[3-Chloro-4-(4-methoxy-phenylsulfanyl)-5-trifluoromethyl-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N 3 -[3,5-Dichloro-4(4-methoxy-benzenesulfonyl)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N 3[ 3,5-Dichloro-4(4-methanesulfonyl-phenoxy)-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N 3 -[3-Chloro-4-(4-methanesulfonyl-phenoxy)-5-tiifluoromethyl-phenyl]-1H-[1,2,4]triazole-3,5-diamine;   N 3 (3-Benzyloxy-5-chloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N 3 -(3-Chloro-4-phenylsulfanyl-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N 3 -(4-Benzenesulfonyl-3-chloro-phenyl)-1H-[1,2,4]triazole-3,5-diamine;   N 3 -(3-Chloro-4-phenylsulfanyl-phenyl)-N 3 -methyl-1H-[1,2,4]triazole-3,5-diamine;   N 3 -(3-Chloro-5-phenoxy-phenyl)-1H-[1,2,4]triazole-3,5-diamine; and   N 3 -[3,5-Dichloro-4-(pyridin-2-yloxy)-phenyl]-1H-[1,2,4]triazole-3,5-diamine.   
     
     
         13 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 . 
     
     
         14 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 2 . 
     
     
         15 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 3 . 
     
     
         16 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 4 . 
     
     
         17 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 5 . 
     
     
         18 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 6 . 
     
     
         19 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 7 . 
     
     
         20 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 8 . 
     
     
         21 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 9 . 
     
     
         22 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 10 . 
     
     
         23 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 11 . 
     
     
         24 . A method for preventing a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 12 . 
     
     
         25 . The method of  claim 1 , further comprising administering to a patient in need thereof a therapeutically effective amount of an immune system suppressant. 
     
     
         26 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1 . 
     
     
         27 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 2 . 
     
     
         28 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 3 . 
     
     
         29 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 4 . 
     
     
         30 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of any one of  claim 5 . 
     
     
         31 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 6 . 
     
     
         32 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 6 . 
     
     
         33 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 7 . 
     
     
         34 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 8 . 
     
     
         35 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 9 . 
     
     
         36 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 10 . 
     
     
         37 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 11 . 
     
     
         38 . A method for treating a Hepatitis C Virus (HCV) infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 12 . 
     
     
         39 . The method of  claim 1 , further comprising administering a combination of antiviral agents that inhibits replication of HCV. 
     
     
         40 . The method of  claim 1 , further comprising administering an immune system modulator or an antiviral agent that inhibits replication of HCV, or a combination thereof. 
     
     
         41 . The method of  claim 39 , wherein the immune system modulator is an interferon or a chemically derivatized interferon. 
     
     
         42 . The method of  claim 38 , wherein the antiviral agent is selected from the group consisting of a HCV protease inhibitor, a HCV polymerase inhibitor, a HCV helicase inhibitor, a HCV NS5A inhibitor, or any combination thereof. 
     
     
         43 . A composition comprising a compound of  claim 1  and a pharmaceutically acceptable excipient.

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