AZEPANE DERIVATIVES AND METHODS OF TREATING HEPATITIS B INFECTIONS

摘要

Provided herein are compounds useful for the treatment of HBV infection in a subject in need thereof, pharmaceutical compositions thereof, and methods of inhibiting, suppressing, or preventing HBV infection in the subject.

主权项

1. A compound of Formula II: or a pharmaceutically acceptable salt thereof, wherein: X is C or N; one of Y or Z is N, and the other is C; L1 is —C(O)NR′—, —SO2NR1—, —C(O)—, —C(O)O—, or —SO2—; Rx is independently, at each occurrence, halo, —CN, —NO2, —C1-6 haloalkyl, —C1-6 dihaloalkyl, —C1-6 trihaloalkyl, -(L2)q-C(═O)R2, -(L2)qCO2R3, or -(L2)q-C(═O)N(R3)2; Ry is independently, at each occurrence, C1-6 alkyl, halo, —CN, —NO2, -(L2)q-OR3, -(L2)q-SR2, -(L2)q-S(═O)R2, -(L2)q-S(═O)2R2, -(L2)q-NHS(═O)2R2, -(L2)q-C(═O)R2, -(L2)q-OC(═O)R2, -(L2)qCO2R3, -(L2)q-00O2R3, -(L2)q-N(R3)2, -(L2)q-C(═O)N(R3)2, -(L2)q-OC(═O)N(R3)2, -(L2)q-NHC(═O)NH(R3), -(L2)q-NHC(═O)R2, -(L2)q-NHC(═O)OR2, -(L2)q-C(OH)(R3)2, -(L2)qC(NH2)(R3)2, —C1-6 haloalkyl, —C1-6 dihaloalkyl, —C1-6 trihaloalkyl, C3-7 cycloalkyl, a C3-10 heterocycloalkyl, aryl, heteroaryl, —C1-4 alkylene-(C3-7 cycloalkyl), —C1-4 alkylene-(C3-10 heterocycloalkyl), —C1-4 alkylene-(aryl), or —C1-4 alkylene-(heteroaryl); or: two Ry groups on adjacent carbon atoms are taken together to form a fused ring; or two Ry groups on non-adjacent carbon atoms are taken together to form a bridge of a bridged bicyclic group; or two Ry groups on the same carbon atom, together with that carbon atom, form C(O); Rz is independently, at each occurrence, C1-6 alkyl, halo, —CN, —NO2, -(L2)q-OR3, -(L2)q-SR2, -(L2)q-S(═O)R2, -(L2)q-S(═O)2R2, -(L2)q-NHS(═O)2R2, -(L2)q-C(═O)R2, -(L2)q-OC(═O)R2, -(L2)crO2R3, -(L2)q-OCO2R3, -(L2)q-N(R3)2, -(L2)q-C(═O)N(R3)2, -(L2)q-OC(═O)N(R3)2, -(L2)q-NHC(═O)NH(R3), -(L2)q-NHC(═O)R2, -(L2)q-NHC(═O)OR2, -(L2)q-C(OH)(R3)2, -(L2)qC(NH2)(R3)2, —C1-6 haloalkyl, —C1-6 dihaloalkyl, —C1-6 trihaloalkyl, C3-7 cycloalkyl, a C3-10 heterocycloalkyl, aryl, heteroaryl, —C1-4 alkylene-(C3-7 cycloalkyl), —C1-4 alkylene-(C3-10 heterocycloalkyl), —C1-4 alkylene-(aryl), or —C1-4 alkylene-(heteroaryl); L2 is independently, at each occurrence, a bivalent radical selected from —(C1-3 alkylene)-, —(C3-7 cycloalkylene)-, —(C1-3 alkylene)q-O—(C1-3 alkylene)q-, or —(C1-3 alkylene)q-NH—(C1-3 alkylene)q-; R1 is H or C1-6-alkyl; R2 is C1-6 alkyl, —C1-6 haloalkyl, —C1-6 dihaloalkyl, —C1-6 trihaloalkyl, C3-7 cycloalkyl, C3-10 heterocycloalkyl, aryl, heteroaryl, —C1-4 alkylene-(C3-7 cycloalkyl), —C1-4 alkylene-(C3-10 heterocycloalkyl), —C1-4 alkylene-(aryl), or —C1-4 alkylene-(heteroaryl); each R3 is independently, at each occurrence, H, C1-6 alkyl, —C1-6 haloalkyl, —C1-6 dihaloalkyl, —C1-6 trihaloalkyl, C3-7 cycloalkyl, C3-10 heterocycloalkyl, aryl, heteroaryl, —C1-4 alkylene-(C3-7 cycloalkyl), —C1-4 alkylene-(C3-10 heterocycloalkyl), —C1-4 alkylene-(aryl), or —C1-4 alkylene-(heteroaryl); m is 1, 2, or 3; n is 0, 1, 2, or 3; p is 1, 2, or 3; and q is 0 or 1.