Compounds and methods for treating fibrosis or cancer

Patent metadata

Field	Value
Publication number	US-2021009551-A1
Application number	US-201716305172-A
Country	US
Kind code	A1
Filing date	Jun 2, 2017
Priority date	Jun 2, 2016
Publication date	Jan 14, 2021
Grant date	—

Abstract

Provided herein, inter alia, are methods and compounds for treating a pulmonary disease, fibrosis, or cancer.

First claim

1 . A compound having the formula:

wherein,
R 1 is independently hydrogen, halogen, —CX 1 3 , —CHX 1 2 , —CH 2 X 1 , —OCX 1 3 , —OCH 2 X 1 , —OCHX 1 2 , —CN, —N 3 , —SR 1D , —ONR 1A R 1B , —NHC(O)NR 1A R 1B , —NR 1A R 1B , —C(O)R 1C , —C(O)OR 1C , —C(O)NR 1A R 1B , —OR 1D , —NR 1A C(O)R 1C , —NR 1A C(O)OR 1C , —NR 1A OR 1C , R 20 -substituted or unsubstituted C 1 -C 4 alkyl, R 20 -substituted or unsubstituted 2 to 4 membered heteroalkyl;
R 20 is independently oxo, halogen, —CX 20 3 , —CHX 20 2 , —CH 2 X 20 , —OCX 20 3 , —OCH 2 X 20 , —OCHX 20 2 , —CN, —N 3 , —SR 20H , —ONR 20E R 20F , —NHC(O)NR 20E R 20F , —NR 20E R 20F , —C(O)R 20G , —C(O)OR 20G , —C(O)NR 20E R 20F , —OR 20H , —NR 20E C(O)R 20G , —NR 20E C(O)OR 20G , —NR 20E OR 20G , unsubstituted C 1 -C 6 alkyl, or unsubstituted 2 to 6 membered heteroalkyl;
R 2 is independently hydrogen, halogen, —CX 2 3 , —CHX 2 2 , —CH 2 X 2 , —OCX 2 3 , —OCH 2 X 2 , —OCHX 2 2 , —CN, —N 3 , —SR 2D , —ONR 2A R 2B , —NHC(O)NR 2A R 2B , —NR 2A R 2B , —C(O)R 2C , —C(O)OR 2C , —C(O)NR 2A R 2B , —OR 2D , —NR 2A C(O)R 2C , —NR 2A C(O)OR 2C , —NR 2A OR 2C , R 23 -substituted or unsubstituted C 1 -C 4 alkyl, or R 23 -substituted or unsubstituted 2 to 4 membered heteroalkyl;
R 23 is independently oxo, halogen, —CX 23 3 , —CHX 23 2 , —CH 2 X 23 , —OCX 23 3 , —OCH 2 X 23 , —OCHX 23 2 , —CN, —N 3 , —SR 23H , —ONR 23E R 23F , —NHC(O)NR 23E R 23F , —NR 23E R 23F , —C(O)R 23G , —C(O)OR 23G , —C(O)NR 23E R 23F , —OR 23H , —NR 23E C(O)R 23G , —NR 23E C(O)OR 23G , —NR 23E OR 23G , unsubstituted C 1 -C 6 alkyl, or unsubstituted 2 to 6 membered heteroalkyl;
R 3A , R 3B , R 3C , R 3D , R 3E , and R 3F are independently —OH, —NH 2 , hydrogen, —CX 3 3 , —CN, —N 3 , —COOH, —CONH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
L 1 is a R 26 -substituted or unsubstituted 2 to 9 membered heteroalkylene, R 26 -substituted C 2 -C 9 alkylene, or R 26 -substituted or unsubstituted C 4 -C 6 cycloalkylene;
R 26 is independently —C(O)R 26C , —COOR 26C , —N 3 , —CONR 26A R 26B , —NR 26D C(O)NR 26A R 26B , or —NR 26A C(O)OR 26C ;
R 1A , R 1B , R 1C , R 1D , R 2A , R 2B , R 2C , R 2D , R 20E , R 20F , R 20G , R 20H , R 23E , R 23F , R 23G , and R 23H are independently hydrogen, —CX 3 , —CN, —COOH, —CONH 2 , unsubstituted C 1 -C 6 alkyl, unsubstituted 2 to 6 membered heteroalkyl, unsubstituted C 3 -C 6 cycloalkyl, unsubstituted 3 to 6 membered heterocycloalkyl, unsubstituted phenyl, or unsubstituted 5 to 6 membered heteroaryl;
R 1A and R 1B substituents bonded to the same nitrogen atom may optionally be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl or unsubstituted 5 to 6 membered heteroaryl; R 2A and R 2B substituents bonded to the same nitrogen atom may optionally be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl or unsubstituted 5 to 6 membered heteroaryl; R 20E and R 20F substituents bonded to the same nitrogen atom may optionally be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl or unsubstituted 5 to 6 membered heteroaryl; R 23E and R 23F substituents bonded to the same nitrogen atom may optionally be joined to form an unsubstituted 3 to 6 membered heterocycloalkyl or unsubstituted 5 to 6 membered heteroaryl;
R 26A is independently hydrogen, —CF 3 , —CN, —COOH, —CONH 2 , R 27A -substituted or unsubstituted C 1 -C 8 alkyl, R 27A -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 27A -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 27A -substituted or unsubstituted 3 to 8 membered heterocycloalkyl, R 27A -substituted or unsubstituted C 6 -C 10 aryl, or R 27A -substituted or unsubstituted 5 to 10 membered heteroaryl;
R 26B is independently hydrogen, —CF 3 , —CN, —COOH, —CONH 2 , R 27B -substituted or unsubstituted C 1 -C 8 alkyl, R 27B -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 27B -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 27B -substituted or unsubstituted 3 to 8 membered heterocycloalkyl, R 27B -substituted or unsubstituted C 6 -C 10 aryl, or R 27B -substituted or unsubstituted 5 to 10 membered heteroaryl;
R 26C is independently R 27C -substituted or unsubstituted C 1 -C 8 alkyl, hydrogen, oxo, halogen, —CF 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —SH, —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , R 27C -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 27C -substituted or unsubstituted C 3 -C 5 cycloalkyl, R 27C -substituted or unsubstituted 3 to 8 membered heterocycloalkyl, R 27C -substituted or unsubstituted C 6 -C 10 aryl, or R 27C -substituted or unsubstituted 5 to 10 membered heteroaryl;
R 26D is independently hydrogen, —CF 3 , —CN, —COOH, —CONH 2 , R 27D -substituted or unsubstituted C 1 -C 8 alkyl, R 27D -substituted or unsubstituted 2 to 8 membered heteroalkyl, R 27D -substituted or unsubstituted C 3 -C 8 cycloalkyl, R 27D -substituted or unsubstituted 3 to 8 membered heterocycloalkyl, R 27D -substituted or unsubstituted C 6 -C 10 aryl, or R 27D -substituted or unsubstituted 5 to 10 membered heteroaryl;
R 26A and R 26B substituents bonded to the same nitrogen atom may optionally be joined to form an R 27A -substituted or unsubstituted 3 to 8 membered heterocycloalkyl or R 27A -substituted or unsubstituted 5 to 10 membered heteroaryl;
R 27A , R 27B , R 27C , and R 27D are independently oxo, halogen, —CF 3 , —CN, —N 3 , —OH, —NH 2 , —COOH, —CONH 2 , —SH, —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHC(O)H, —NHC(O)OH, —NHOH, —OCF 3 , —OCHF 2 , —N 3 , unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, unsubstituted C 3 -C 8 cycloalkyl, unsubstituted 3 to 8 membered heterocycloalkyl, unsubstituted C 6 -C 10 aryl, or unsubstituted 5 to 10 membered heteroaryl;
wherein at least one of the R 3A , R 3B , R 3C , R 3D , R 3E , or R 3F substituents are independently —OH; and
each X 1 , X 2 , X 3 , X 20 , and X 23 is independently —F, —Cl, —Br, or —I.

2 . The compound of claim 1 , having the formula:

3 . The compound of claim 1 , wherein R 3A is —NH 2 , —OH, or substituted or unsubstituted heteroalkyl.

4 . (canceled)

5 . The compound of claim 1 , wherein R 3B is —NH 2 , —OH, or substituted or unsubstituted heteroalkyl.

6 . (canceled)

7 . The compound of claim 1 , wherein R 3C is —NH 2 , —OH, or substituted or unsubstituted heteroalkyl.

8 . (canceled)

9 . The compound of claim 1 , wherein R 3D is —NH 2 , —OH, or substituted or unsubstituted heteroalkyl.

10 . (canceled)

11 . The compound of claim 1 , wherein R 3E is —NH 2 , —OH, or substituted or unsubstituted heteroalkyl.

12 . (canceled)

13 . The compound of claim 1 , wherein R 3F is —NH 2 , —OH, or substituted or unsubstituted heteroalkyl.

14 . (canceled)

15 . The compound of claim 1 having the formula:

16 . The compound of claim 15 having the formula:

Assignees

• Univ California

Inventors

• Chapman Harold A
• Wei Ying
• Backes Bradley J

Classifications

• A61K31/353

  3,4-Dihydrobenzopyrans, e.g. chroman, catechin · CPC title

• C07D323/00 Primary

  Heterocyclic compounds containing more than two oxygen atoms as the only ring hetero atoms · CPC title

• C07D273/01 Primary

  having one nitrogen atom · CPC title

• C07D321/10

  condensed with carbocyclic rings or ring systems · CPC title

• C07D321/00

  Heterocyclic compounds containing rings having two oxygen atoms as the only ring hetero atoms, not provided for by groups C07D317/00 - C07D319/00 · CPC title