Hepatitis B core protein allosteric modulators

A method of treating a hepatitis B infection in a patient in need thereof, comprising administering to the patient an effective amount of a compound of Formula 1:

• wherein:
• T is selected from the group consisting of —C(O)—, —CH2—C(O)—, —N(C(O)—CH3)—, —NH—, —O—, and —S(O)z—, where z is 0, 1 or 2;
• Y is NRY;
• RY is selected from the group consisting of H, methyl, ethyl, propyl, phenyl and benzyl;
• RL is selected from the group consisting of H, methyl, and —C(O)—C1-3alkyl;
• L is a bond or C1-4 straight chain alkylene optionally substituted by one or two substituents each independently selected from the group consisting of methyl (optionally substituted by halogen or hydroxyl), ethenyl, hydroxyl, NR′R″, phenyl, heterocycle, and halogen and wherein the C1-4 straight chain alkylene may be interrupted by an —O—;
• R2 is selected from the group consisting of:
• i) H,
• ii) phenyl or naphthyl (wherein the phenyl or naphthyl may be optionally substituted with one, two, three or more substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, NR′R″, —C(O)—NR′R″, —C(O)—C1-6alkyl, —C(O)—C1-6alkoxy, phenyl (optionally substituted by one, two or three substituents each independently selected from the group consisting of halogen, hydroxyl, cyano, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, NR′R″, C(O)—NR′R″, —C(O)—C1-6alkoxy, —S(O)w—C1-6alkyl (where w is 1, 2 or 3), S(O)w—NR′R″ (where w is 1, 2 or 3), —NR′—S(O)w and —S(O)w—NR′R″ (where w is 1, 2 or 3)), heteroaryl (optionally substituted by one, two or three substituents each independently selected from the group consisting of halogen, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, NR′R″, C(O)—NR′R″, —C(O)—C1-6alkyl, —C(O)—C1-6alkoxy, —S(O)w—C1-6alkyl (where w is 1, 2 or 3), NR′—S(O)w, and —S(O)w—NR′R″ (where w is 1, 2 or 3)), C3-6cycloalkyl, —S(O)w—C1-6alkyl (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)),
• iii) 5-6 membered heteroaryl having one, two, or three heteroatoms each independently selected from O, N and S (wherein the 5-6 membered heteroaryl may be optionally substituted:
• a) on a carbon with one, two, or three substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, phenyl (optionally substituted by one, two or three substituents each independently selected from the group consisting of halogen, hydroxyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, NR′R″, C(O)—NR′R″, —C(O)—OH, —C(O)—C1-6alkoxy, —S(O)w—C1-6alkyl (where w is 1, 2 or 3), —NR′—S(O)w, and —S(O)w—NR′R″ (where w is 1, 2 or 3)), heteroaryl, heterocycle, NR′R″, —C(O)—NR′R″, —C(O)—C1-6alkoxy, —S(O)w—C1-6alkyl (where w is 1, 2 or 3), —NR′—S(O)w, and —S(O)w—NR′R″ (where w is 1, 2 or 3), and/or b) on a nitrogen by R′),
• iv) C1-6alkyl, C1-6alkoxy, C2-6alkenyl, C3-10 cycloalkyl (optionally substituted with one, two, or three substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, NR′R″, —C(O)—NR′R″, —CNR′, C1-6alkoxy, —C(O)—C1-6alkyl, and —C(O)—C1-6alkoxy, and wherein the C3-10 cycloalkyl may optionally be a bridged cycloalkyl), and
• v) a 4-6 membered heterocycloalkyl having one or two heteroatoms each independently selected from O, N and S (wherein the 4-6 membered heterocycloalkyl may be optionally substituted with one, two, or three substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, NR′R″, —C(O)—NR′R″, C1-6alkyl, C1-6alkoxy, —C(O)—C1-6alkyl, and —C(O)—C1-6alkoxy);
• R′ is selected, independently for each occurrence, from H, methyl, ethyl, propyl, phenyl, and benzyl;
• R″ is selected, independently for each occurrence, from H, methyl, ethyl, propyl, butyl, carboxybenzyl, —C(O)-methyl and —C(O)-ethyl, or R′ and R″ taken together may form a 4-6 membered heterocycle;
• each of moieties R4, R5, R6, R7, R8, R9, and R10 are independently selected for each occurrence from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, halogen, hydroxyl, nitro, cyano, NR′R″, —C(O)—NR′R″, —S(O)w—C1-6alkyl (where w is 1, 2 or 3), —NR′—S(O), and —S(O)w—NR′R″ (where w is 0, 1 or 2), C1-6alkoxy, —C(O)—OH, —C(O)—C1-6alkyl, and —C(O)—C1-6alkoxy;
• wherein for each occurrence in any one or more of R2, R4, R5, R6, R7, R8, R9, and R10:
• i) C1-6alkyl may be optionally substituted with one, two, or three substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, phenyl, NR′R″, —C(O)—NR′R″, S(O)w-methyl (where w is 1, 2 or 3), —NR′—S(O), and S(O)w—NR′R″ (where w is 0, 1 or 2);
• ii) C1-6alkoxy may be optionally substituted with one, two, or three substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C1-6alkyl, phenyl, NR′R″, —C(O)—NR′R″, S(O)w—C1-6alkyl (where w is 1, 2 or 3), —NR′—S(O)w, and S(O)w—NR′R″ (where w is 0, 1 or 2);
• and
• iii) C3-6cycloalkyl may be optionally substituted with one, two, or three substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C1-6alkyl, C1-6alkoxy, —C(O)—C1-6alkyl, —C(O)—C1-6alkoxy, and NR′R″;
• or
• a pharmaceutically acceptable salt thereof.