Hepatitis b core protein allosteric modulators

Abstract

The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.

1 - 69 . (canceled) 
     
     
         70 . A compound of Formula 7: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein 
         Y is S(O) y , wherein y is 2; 
         each of R m  and R m′  independently is selected from the group consisting of H, halogen, C 1-6  alkyl (optionally substituted by one, two or three substituents each independently selected from halogen and hydroxyl), C 2-6  alkenyl (optionally substituted by one, two or three substituents each independently selected from halogen and hydroxyl), NR′R″, and hydroxyl; 
         R c  is H or C 1-6  alkyl; 
         each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  independently is selected from the group consisting of hydrogen, C 1-6  alkyl, C 2-6  alkynyl, C 2-6  alkenyl, halogen, hydroxyl, nitro, cyano, and NR′R″; 
         R 78  is selected from the group consisting of H, halogen, hydroxyl, nitro, cyano, carboxy, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, NR′R″, —C(O)—C 1-6  alkyl, —C(O)—C 1-6  alkoxy, phenyl, heteroaryl, C 3-6  cycloalkyl, —S(O)w-C 1-6  alkyl (where w is 1, 2 or 3), —S(O)w-NR′R″ (where w is 1, 2 or 3), and —NR′—S(O)w, (where w is 1, 2 or 3); 
         R 79  is selected from the group consisting of H, halogen, hydroxyl, nitro, cyano, carboxy, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, NR′R″, —C(O)—C 1-6  alkyl, —C(O)—C 1-6  alkoxy, phenyl, heteroaryl, C 3-6  cycloalkyl, —S(O)w-C 1-6  alkyl (where w is 1, 2 or 3), —S(O)w-NR′R″ (where w is 1, 2 or 3), and —NR′—S(O)w, (where w is 1, 2 or 3); 
         each R′ independently is selected from the group consisting of H, methyl, ethyl, and propyl; 
         each R″ is independently selected from H, methyl, ethyl, propyl, butyl, —C(O)-methyl and —C(O)-ethyl, or R′ and R″ taken together with the nitrogen to which they are attached may form a 4-6 membered heterocycle; and 
         for each occurrence, C 1-6  alkyl may be optionally substituted with one, two, or three halogens. 
       
     
     
         71 . The compound of  claim 70 , wherein R c  is H or methyl. 
     
     
         72 . The compound of  claim 70 , wherein R c  is H. 
     
     
         73 . The compound of  claim 70 , wherein R 7  is selected from the group consisting of H and F. 
     
     
         74 . The compound of  claim 70 , wherein R 6  is selected from the group consisting of H and F. 
     
     
         75 . The compound of  claim 70 , wherein R 5  is selected from the group consisting of H and F. 
     
     
         76 . The compound of  claim 70 , wherein R 10  is selected from the group consisting of H, methyl, and F. 
     
     
         77 . The compound of  claim 70 , wherein each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  is H. 
     
     
         78 . The compound of  claim 70 , wherein each of R 78  and R 79  independently is selected from the group consisting of H, methyl, ethyl, propyl, CF 3 , CH 2 CF 3 , Cl, F, phenyl, NH 2 , OCH 3 , NHCH 3 , and N(CH 3 ) 2 . 
     
     
         79 . A pharmaceutically acceptable composition comprising a compound of  claim 70 , and a pharmaceutically acceptable excipient. 
     
     
         80 . A method of treating a hepatitis B infection in a patient in need thereof, comprising administering an effective amount of a compound of  claim 70 . 
     
     
         81 . The method of  claim 80 , further comprising administering one or more additional active compounds. 
     
     
         82 . The method of  claim 80 , further comprising administering one or more additional HBV capsid assembly promoter. 
     
     
         83 . The method of  claim 80 , further comprising administering one or more other HBV agent each selected from the group consisting of HBV capsid assembly promoters, HBF viral polymerase interfering nucleosides, viral entry inhibitors, HBsAg secretion inhibitors, disruptors of nucleocapsid formation, cccDNA formation inhibitors, antiviral core protein mutant, HBc directed transbodies, RNAi targeting HBV RNA, immunostimulants, TLR-7/9 agonists, cyclophilin inhibitors, HBV vaccines, SMAC mimetics, epigenetic modulators, kinase inhibitors, and STING agonists.