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US 2019/0375708 A1Published application
Hepatitis b capsid assembly modulators
AssigneeVenatorx Pharmaceuticals, Inc.
InventorsChristopher J. BURNS, Glen COBURN, Bin LIU, Jiangchao YAO, Christopher BENETATOS, Steven A. BOYD, Stephen M. CONDON, Thomas HAIMOWITZ
Life of this patent
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Abstract
Described herein are hepatitis B capsid assembly modulators and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of hepatitis B.
Claims20
A compound of Formula (I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:
- wherein:
- Ring A is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;
- each R11 is independently halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRbRc, —OC(═O)NRbRc, —NRbC(═O)NRbRc, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C1-C6alkyl(aryl), —C1-C6alkyl(heteroaryl), —C1-C6alkyl(cycloalkyl), or —C1-C6alkyl(heterocycloalkyl);
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R1;
- or two R11 on adjacent atoms are taken together with the atoms to which they are attached to form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- each optionally substituted with one, two, or three R2;
- R12 is hydrogen or C1-C6alkyl;
- R13 is hydrogen, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRbRc, —OC(═O)NRbRc, —NRbC(═O)NRbRc, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C1-C6alkyl(aryl), —C1-C6alkyl(heteroaryl), —C1-C6alkyl(cycloalkyl), or —C1-C6alkyl(heterocycloalkyl);
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R3;
- R14 is hydrogen, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb,—C(═O)NRbRc, —OC(═O)NRbRc, —NRbC(═O)NRbRc, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C1-C6alkyl(aryl), —C1-C6alkyl(heteroaryl), —C1-C6alkyl(cycloalkyl), or —C1-C6alkyl(heterocycloalkyl);
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R4;
- R15 is hydrogen, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —C(═O)ORb, —C(═O)NRbRc, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C1-C6alkyl(aryl), —C1-C6alkyl(heteroaryl), —C1-C6alkyl(cycloalkyl), or —C1-C6alkyl(heterocycloalkyl);
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R5;
- R16 is hydrogen, —CN, —OR20, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, —C1-C6alkyl(aryl), —C1-C6alkyl(heteroaryl), —C1-C6alkyl(cycloalkyl), or —C1-C6alkyl(heterocycloalkyl);
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R7;
- R17 is C1-C6hydroxyalkyl, cycloalkyl, or heterocycloalkyl;
- each optionally substituted with one, two, or three R7;
- each R20 is independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R7;
- n is 0-4;
- each R1, R2, R3, R4, and R5 is independently oxo, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRbRc, —OC(═O)NRbRc, —NRbC(═O)NRbRc, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C1-C6alkyl(aryl), —C1-C6alkyl(heteroaryl), —C1-C6alkyl(cycloalkyl), or —C1-C6alkyl(heterocycloalkyl);
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three oxo, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
- each R7 is independently oxo, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRc, —B(ORb)(ORc), —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRbRc, —OC(═O)NRbRc, —NRbC(═O)NRbC, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, —C1-C6alkyl(aryl), —C1-C6alkyl(heteroaryl), —C1-C6alkyl(cycloalkyl), or —C1-C6alkyl(heterocycloalkyl);
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R7a;
- each R7a is independently oxo, halogen, —CN, —OH, —ORa, —NRbRc, —C(═O)Ra, —C(═O)ORb, C(═O)NRbRc, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three oxo, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
- each Ra is independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three oxo, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
- and
- each Rb and Rc are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
- wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three oxo, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
- or Rb and Rc are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three oxo, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl.
29 more elements
(canceled)
(canceled)
Dependencies are inferred from the claim text.