Hepatitis b core protein modulators

Patent metadata

Field	Value
Publication number	US-2018258084-A1
Application number	US-201615760284-A
Country	US
Kind code	A1
Filing date	Sep 15, 2016
Priority date	Sep 15, 2015
Publication date	Sep 13, 2018
Grant date	—

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.

First claim

1 . A compound represented by:

wherein
Y is S(O) y , wherein y is 2;
R Z is H;
R m′ and R m are H;
R c is H;
R 77 is selected from the group consisting of H, halogen, cyano, and C 1-6 alkyl;
R 78 is selected from the group consisting of C 1-6 alkyl substituted with one, two, or three substituents each independently selected from the group consisting of halogen, hydroxyl, and cyano; phenyl substituted with one, two, three or four substituents each independently selected from the group consisting of R 73 ; and X 2 —C 1-6 alkylene-R 79 ;
X 2 is selected from the group consisting of S(O) w (wherein w is 0, 1, or 2), O, —C(O)— and NR′;
R 79 is selected from the group consisting of H, hydroxyl, halogen, C 1-6 alkyl, —C(O)—O—C 1-6 alkyl, heterocycle (optionally substituted by one or more substituents selected from the group consisting of halogen, NR′R′, —C(O)—O—C 1-6 alkyl, carboxy and C 1-6 alkyl), —C(O)—NR′R″, —C (═NH)—NR′R″, heteroaryl, phenyl (optionally substituted by one or more substituents selected from the group consisting of halogen, NR′R′, —C(O)—O—C 1-6 alkyl, carboxy, C 1-6 alkoxy, and C 1-6 alkyl), C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, carboxy, NR′R″, —C(O)—C 1-6 alkyl, C 3-6 cycloalkyl, —NR′—C(O)— C 1-6 alkyl, NR′—C(O)— O—C 1-6 alkyl, —S(O) w —C 1-6 alkyl (where w is 0, 1 or 2), —S(O) w —NR′R″ (where w is 0, 1 or 2), and —NR′—S(O) w — C 1-6 alkyl (where w is 0, 1 or 2));
R 73 is selected from the group consisting of H, halogen, hydroxyl, nitro, cyano, carboxy, oxo, C 1-6 alkyl, —C(O)—O—C 1-6 alkyl, heterocycle (optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxyl, oxo, NR′R′, —C(O)—O—C 1-6 alkyl, carboxy and C 1-6 alkyl), —C(O)—NR′—C 1-6 alkyl, —C(═NH)—NR′R″, heteroaryl, phenyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, carboxy, oxo, NR′R″, —C(O)—C 1-6 alkyl, —C 3-6 cycloalkyl, NR′—C(O)— C 1-6 alkyl, NR′—C(O)— O—C 1-6 alkyl, —S(O) w —C 1-6 alkyl (where w is 0, 1 or 2), —S(O) w —NR′R″ (where w is 1, 2 or 3), —NR′—S(O) w — C 1-6 alkyl (where w is 0, 1 or 2), C(O)—NR′— C 1-6 alkyl, C(O)—C 1-3 alkylene-NR′— C(O)—O— C 1-6 alkyl, X 2 — R 79 ; and X 2 —C 1-6 alkylene-R 79 ;
R′ is selected, independently for each occurrence, from H, methyl, ethyl, cyclopropyl, cyclobutyl, and propyl;
R″ is selected, independently for each occurrence, from H, methyl, ethyl, propyl, (optionally substituted by hydroxyl), butyl (optionally substituted by hydroxyl), —C(O)-methyl and —C(O)-ethyl, or R′ and R″ taken together with the nitrogen to which they are attached may form a 4-7 membered heterocycle optionally substituted by one, two or more substituents selected from the group consisting of halogen, hydroxyl, NH 2 , —C(O)—O—C 1-3 alkyl, —C(O)—C 1-3 alkyl, carboxy, oxo, and C 1-3 alkyl;
each of moieties R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is independently selected for each occurrence from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkynyl, C 2-6 alkenyl, halogen, hydroxyl, nitro, cyano, and NR′R″;
wherein for each occurrence, C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl may be optionally substituted with one, two, three or more substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C 3-6 cycloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, NR′R″, —NR′—S(O) w — C 1-2 alkyl (where w is 0, 1 or 2), NR′—C(O)—C 1-3 alkyl, NR′—C(O)— O—C 1-3 alkyl, and S(O) w —NR′R″ (where w is 0, 1 or 2); C 1-6 alkoxy may be optionally substituted with one, two, three or more substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C 1-3 alkyl, NR′R″, —NR′—S(O) w — C 1-2 alkyl (where w is 0, 1 or 2), and S(O) w —NR′R″ (where w is 0, 1 or 2); C 1-6 alkylene may be optionally substituted by a substituent selected from the group consisting of C 3-6 cycloalkyl, hydroxyl, cyano, and halogen;
and pharmaceutically acceptable salts and N-oxides thereof.

2 - 10 . (canceled)

11 . The compound of claim 1 , wherein R 78 is selected from the group consisting of CF 3 , cyano, and phenyl substituted with one, two, three or four substituents each independently selected from the group consisting of R 73 .

12 - 13 . (canceled)

14 . The compound of claim 1 , wherein R 77 is selected from the group consisting of H, CH 3 and CF 3 .

15 . The compound of claim 1 , wherein R 7 is H or halogen.

16 . The compound of claim 1 , wherein R 10 is H, halogen or methyl.

17 - 18 . (canceled)

19 . The compound of claim 1 , wherein each of R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is H.

20 . The compound of claim 1 , wherein R 77 is H.

21 - 23 . (canceled)

24 . A pharmaceutically acceptable composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.

25 . A method of treating a hepatitis B infection in a patient in need thereof, comprising administering an effective amount of a compound of claim 1 .

26 - 28 . (canceled)

Assignees

• Assembly Biosciences Inc
• Univ Indiana Res & Tech Corp
• Indiana Univ Research And Technology Corpora Tion

Inventors

• Turner William
• Arnold Lee Daniel
• Maag Hans
• Li Leping
• Bures Mark
• Haydar Simon
• Francis Samson

Classifications

• A61P31/22

  for herpes viruses · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D267/20

  [b, f]-condensed · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title