Methods and compositions for modulating Ire1, SRC and ABL activity

Patent metadata

Field	Value
Publication number	US-9382230-B2
Application number	US-201414322765-A
Country	US
Kind code	B2
Filing date	Jul 2, 2014
Priority date	Sep 15, 2008
Publication date	Jul 5, 2016
Grant date	Jul 5, 2016

Abstract

Disclosed herein are, inter alia, compositions for modulating Ire1, Src, or Abl, methods for identifying modulating activity in test compounds, and methods for treating diseases caused by the activity or inactivity of Ire1, Src, or Abl.

First claim

What is claimed is:

1. A method of treating a Parkinson's disease caused by abnormal Ire1 activity in a subject in need of such treatment, said method comprising administering to said subject a therapeutically effective amount of a compound having the formula:

wherein,
R 1 is hydrogen,

halogen, —CN, —NO, —NO 2 , —NR 9 R 10 , —OR 11 , —COOR 12 , —SR 13 , —COR 14 , 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;
R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 are independently hydrogen, 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 is —NH—C(O)—NH—;
A is aryl or heteroaryl;
R 37 is halogen, —CN, —CF 3 , —OH, —NH 2 , —SO 2 , —COOH, 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; and
w is an integer from 0 to 5.

2. The method of claim 1 , wherein R 1 is substituted or unsubstituted C 1 -C 5 alkyl, substituted or unsubstituted 2 to 5 membered heteroalkyl, substituted or unsubstituted C 3 -C 6 cycloalkyl, substituted or unsubstituted 5 or 6 membered heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.

3. The method of claim 1 , wherein R 1 is cyclopropyl.

4. The method of claim 1 , wherein A is aryl.

5. The method of claim 1 , wherein A is phenyl.

6. The method of claim 1 , wherein A is a fused ring aryl or fused ring heteroaryl.

7. The method of claim 1 , wherein R 37 is halogen, —CN, —CF 3 , —OH, —NH 2 , —SO 2 , —COOH, R 40 -substituted or unsubstituted alkyl, R 40 -substituted or unsubstituted heteroalkyl, R 40 -substituted or unsubstituted cycloalkyl, R 40 -substituted or unsubstituted heterocycloalkyl, R 40 -substituted or unsubstituted aryl, or R 40 -substituted or unsubstituted heteroaryl; and R 40 is
halogen, —CN, —CF 3 , —OH, —NH 2 , —SO 2 , —COOH, unsubstituted alkyl, unsubstituted heteroalkyl, unsubstituted cycloalkyl, unsubstituted heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl.

8. The method of claim 7 , wherein R 40 is halogen, —CN, —CF 3 , —OH, —NH 2 , —SO 2 , —COOH, unsubstituted C 1 -C 8 alkyl, unsubstituted 2 to 8 membered heteroalkyl, C 3 -C 7 unsubstituted cycloalkyl, unsubstituted 3 to 7 membered heterocycloalkyl, unsubstituted aryl, or unsubstituted heteroaryl.

9. The method of claim 1 , wherein R 37 is substituted or unsubstituted C 1 -C 8 alkyl or substituted or unsubstituted 2 to 8 membered heteroalkyl.

10. The method of claim 1 , wherein R 37 is unsubstituted C 1 -C 8 alkyl or unsubstituted 2 to 8 membered heteroalkyl.

11. The method of claim 1 , wherein R 37 is substituted or unsubstituted C 1 -C 4 alkyl.

12. The method of claim 1 , wherein R 37 is —CF 3 .

13. The method of claim 1 , wherein w is 0 or 1.

14. The method of claim 1 , wherein w is 1.

15. The method of claim 1 , wherein the compound has one of the following formulae:

16. The method of claim 1 , wherein the compound has the formula:

Assignees

• Univ California

Inventors

• Walter Peter
• Korennykh Alexei
• Shokat Kevan M
• Zhang Chao
• Finer-Moore Janet
• Stroud Robert
• Egea Pascal
• Korostelev Andrei
• Dar Arvin
• Bernales Sebastian

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title