Hsp90 inhibitors

Patent metadata

Field	Value
Publication number	US-10064867-B2
Application number	US-201615374007-A
Country	US
Kind code	B2
Filing date	Dec 9, 2016
Priority date	Apr 5, 2011
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

The disclosure relates to Compounds of Formula (1):

and pharmaceutically acceptable salts thereof wherein Z 1 , Z 2 , Z 3 , Xa, Xb, Xc, Y, X 2 , and X 4 are as defined herein, compositions comprising an effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof, and methods to treat or prevent a condition, such as cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (1) or a pharmaceutically acceptable salt thereof.

First claim

What is claimed:

1. A method for treating cancer or a neurodegenerative disorder, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (1):

or a pharmaceutically acceptable salt thereof, wherein:
(a) each of Z 1 , Z 2 and Z 3 is independently CH or N;
(b) Y is S;
(c) Xa and Xb are O;
(d) Xc is —CH 2 —;
(e) X 2 is —NR 1 R 2 , wherein R 1 and R 2 are each independently H, C 1-6 alkyl, C 2 -C 6 alkenyl, C 2-6 alkynyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, or alkylheteroarylalkyl;
(f) X 4 is hydrogen or halogen;
(g) R is —R 10 —NH—R 11 wherein R 10 is ethylene or propylene, and
(i) R 11 is isopropyl or t-butyl, or
(ii) R 11 is a branched alkyl, Z 1 , Z 2 and Z 3 are each N, and R 1 and R 2 are each independently alkyl which has 1, 3, 4, 5, or 6 carbon atoms, C 2 -C 6 alkenyl, C 2-6 alkynyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, alkylaryl, arylalkyl, alkylheteroaryl, heteroarylalkyl, or alkylheteroarylalkyl,

wherein the neurodegenerative disorder is selected from the group consisting of spinal and bulbar muscular atrophy (Kennedy's disease), Alzheimer's Disease (AD), dementia of head trauma and diffuse brain damage, dementia pugilistica, traumatic brain injury, frontal lobe dementia, Parkinson's disease, and Huntington disease, and
wherein the cancer is selected from the group consisting of hematopoietic disorders, breast cancer, lung cancer, leukemia, lymphoma, pancreatic cancer, multiple myeloma, prostate cancer, glioma, colon cancer, gastric cancer, and ovarian cancer.

2. The method of claim 1 , wherein X 2 is dimethylamine.

3. The method of claim 1 , wherein R 11 is neopentyl.

4. The method of claim 1 , wherein R 11 is isopropyl.

5. The method of claim 1 , wherein R 11 is t-butyl.

6. The method of claim 1 , wherein Z 1 , Z 2 and Z 3 are each N.

7. The method of claim 1 , wherein Z 1 , Z 2 and Z 3 are each N, X 2 is dimethylamine, Y is S, R 10 is ethylene, R 11 is neopentyl, and X 4 is H.

8. The method of claim 1 , wherein Z 1 , Z 2 and Z 3 are each N, X 2 is dimethylamine, Y is S, R 10 is propylene, R 11 is isopropyl, and X 4 is H.

9. The method of claim 1 , wherein Z 1 , Z 2 and Z 3 are each N, X 2 is dimethylamine, Y is S, R 10 is propylene, R 11 is t-butyl, and X 4 is H.

10. The method of claim 1 , wherein the method is for treating a neurodegenerative disorder.

11. The method of claim 1 , wherein the method is for treating cancer.

12. The method of claim 7 , wherein the method is for treating a neurodegenerative disorder.

13. The method of claim 7 , wherein the method is for treating cancer.

14. The method of claim 8 , wherein the method is for treating a neurodegenerative disorder.

15. The method of claim 8 , wherein the method is for treating cancer.

16. The method of claim 9 , wherein the method is for treating a neurodegenerative disorder.

17. The method of claim 9 , wherein the method is for treating cancer.

18. The method of claim 1 , wherein the neurodegenerative disorder is dementia of head trauma and diffuse brain damage, dementia pugilistica, and/or traumatic brain injury.

19. The method of claim 1 , wherein the hematopoietic disorders are selected from myeloproliferative disorders, myelofibrosis, polycythemia vera, and essential thrombocytosis.

20. The method of claim 10 , wherein the neurodegenerative disorder is Alzheimer's Disease (AD).

Assignees

• Sloan Kettering Inst Cancer Res

Inventors

• Taldone Tony
• Chiosis Gabriela

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• A61P25/16

  Anti-Parkinson drugs · CPC title