Quinazoline Compounds

Abstract

Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.

1 - 43 . (canceled) 
     
     
         44 . A method for treating or preventing an HIV infection in a subject comprising administering to the subject a compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein:
 Q is 
 
       
       
         
           
           
               
               
           
         
         X 1 , X 2 , and X 3  are each independently N or C(R 11 ), provided that, at most 2 of X 1 , X 2 , and X 3  are N; 
         R 1  is —H, —CN, —OR a , —C(O)OR a , halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or C 1-6 heteroalkyl, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, and C 1-6 heteroalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12  groups, which may be same or different; 
         R 2  is —CN; 
         R 3  is —H, —OR a , —SR a , —NR a R b , —NHC(O)NR a R b , C 1-6 alkyl, C 3-10 cycloalkyl, or C 1-6  heteroalkyl, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, and C 1-6 heteroalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12  groups, which may be same or different; 
         R 4  is —H or —OR a ; 
         R 5  is —H, —OR a , halogen, —NO 2 , —CN, —NR a R b , —NHC(O)NR a R b , —OC(O)NR a R b , —CH 2 C(O)NR a R b , C 1-6 alkyl, C 3-10 cycloalkyl, or C 1-6  heteroalkyl, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, and C 1-6  heteroalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12  groups, which may be same or different; 
         R 6  is —H; 
         R 7  is C 1-6 alkyl, halogen, or —OR a ; 
         R 8  is C 1-6 alkyl, halogen, or —OR a ; 
         R 9  is —H, C 1-6 alkyl, or C 3-10 cycloalkyl, wherein each C 1-6 alkyl and C 3-10 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12  groups, which may be same or different; 
         R 10  is —H, C 1-6 alkyl, or C 3-10 cycloalkyl, wherein each C 1-6 alkyl and C 3-10 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12  groups, which may be same or different; 
         each R 11  is independently —H, —CN, —OR a , —C(O)OR a , halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or C 1-6 heteroalkyl, which may be same or different, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, and C 1-6 heteroalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12  groups, which may be same or different; 
         each R 12  is independently C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, 5-10 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, halogen, —OR a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —OC(O)NR a R b , —N a C(O)OR b , —SR a , —S(O) 1-2 R a , —S(O) 2 F, —S(O) 2 NR a R b , —NR a S(O) 2 R b , —N 3 , —CN, or —NO 2 ; wherein each C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, and 5-10 membered heterocyclyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halogen, —OR a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —OC(O)NR a R b , —NR a C(O)OR b , —SR a —S(O) 1-2 R a , —S(O) 2 F, —S(O) 2 NR a R b , —NR a S(O) 2 R b , —N 3 , —CN, and —NO 2 , groups, which may be same or different; 
         each R a  and R b  is independently —H, —NH 2 , C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, 5-10 membered heterocyclyl, C 6-10 aryl, or 5-10 membered heteroaryl, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, 5-10 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 R 13  groups, which may be same or different; or R a  and R b  together with the atoms to which they are attached form a 5-10 membered heterocycle; and 
         each R 13  is independently —CN, halogen, C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, or 5-10 membered heterocyclyl, 
         or a tautomer or a pharmaceutically acceptable salt thereof; 
         in combination with one, two, three, or four additional therapeutic agents independently selected from raltegravir, Truvada® (tenofovir disoproxil fumarate+emtricitabine, TDF+FTC), maraviroc, enfuvirtide, Epzicom® (Livexa®, abacavir sulfate+lamivudine, ABC+3TC), Trizivir® (abacavir sulfate+zidovudine+lamivudine, ABC+AZT+3TC), adefovir, adefovir dipivoxil, Stribild® (elvitegravir+cobicistat+tenofovir disoproxil fumarate+emtricitabine), rilpivirine, rilpivirine hydrochloride, Complera® (Eviplera®, rilpivirine+tenofovir disoproxil fumarate+emtricitabine), Cobicistat, Atripla® (efavirenz+tenofovir disoproxil fumarate+emtricitabine), atazanavir, atazanavir sulfate, dolutegravir, elvitegravir, Aluvia® (Kaletra®, lopinavir+ritonavir), ritonavir, emtricitabine, atazanavir sulfate+ritonavir, darunavir, lamivudine, Prolastin, fosamprenavir, fosamprenavir calcium, efavirenz, Combivir® (zidovudine+lamivudine, AZT+3TC), etravirine, nelfinavir, nelfinavir mesylate, interferon, didanosine, stavudine, indinavir, indinavir sulfate, tenofovir+lamivudine, zidovudine, nevirapine, saquinavir, saquinavir mesylate, aldesleukin, zalcitabine, tipranavir, amprenavir, delavirdine, delavirdine mesylate, Radha-108 (Receptol), Hlviral, lamivudine+tenofovir disoproxil fumarate, efavirenz+lamivudine+tenofovir disoproxil fumarate, phosphazid, lamivudine+nevirapine+zidovudine, abacavir, abacavir sulfate, tenofovir, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir alafenamide, tenofovir alafenamide fumarate, and tenofovir alafenamide hemifumarate. 
       
     
     
         45 - 51 . (canceled) 
     
     
         52 . The method of  claim 44 , wherein one of the additional therapeutic agents is selected from tenofovir alafenamide, tenofovir alafenamide fumarate, and tenofovir alafenamide hemifumarate. 
     
     
         53 . The method of  claim 44 , wherein Q is 
       
         
           
           
               
               
           
         
       
     
     
         54 . The method of  claim 44 , wherein X 1 , X 2 , and X 3  are each CH. 
     
     
         55 . The method of  claim 44 , wherein X 1 , X 2 , and X 3  are C(R 11 ); each R 11  are independently selected from —H, —CN, —OR a , halogen, and C 1-6 alkyl; and R 1  is selected from —H, —CN, —OR a , halogen, and C 1-6 alkyl. 
     
     
         56 . The method of  claim 44 , wherein R 3  is —H, —OR a , —NR a R b , —NHC(O)NR a R b , C 1-6 alkyl, or C 1-6  heteroalkyl. 
     
     
         57 . The method of  claim 44 , wherein R 3  is —NH 2  or —OH. 
     
     
         58 . The method of  claim 44 , wherein R 4  is —H, and R 5  is —H, —OR a , halogen, —NO 2 , —CN, —NR a R b , —NHC(O)NR a R b , or C 1-6 alkyl. 
     
     
         59 . The method of  claim 44 , wherein R 4 , R 5 , and R 6  are —H. 
     
     
         60 . The method of  claim 44 , wherein R 7  is C 1-6 alkyl. 
     
     
         61 . The method of  claim 44 , wherein R 8  is C 1-6 alkyl. 
     
     
         62 . The method of  claim 44 , wherein R 7  and R 8  are C 1-6 alkyl. 
     
     
         63 . The method of  claim 44 , wherein R 7  and R 8  are methyl. 
     
     
         64 . The method of  claim 44 , wherein R 9  is —H or C 1-6 alkyl. 
     
     
         65 . The method of  claim 44 , wherein R 10  is —H or C 1-6 alkyl. 
     
     
         66 . The method of  claim 44 , wherein Q is 
       
         
           
           
               
               
           
         
       
     
     
         67 . The method of  claim 44 , wherein the compound of formula (I), or a tautomer or a pharmaceutically acceptable salt thereof, is a compound of formula: 
       
         
           
           
               
               
           
         
       
       or a tautomer or a pharmaceutically acceptable salt thereof.