Biphenyl amides with modified ether groups as HSP90 inhibitors and HSP70 inducers

Patent metadata

Field	Value
Publication number	US-10590065-B2
Application number	US-201515321289-A
Country	US
Kind code	B2
Filing date	Jun 24, 2015
Priority date	Jun 24, 2014
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

Abstract

Provided herein are compounds of the formulas: (I) wherein: n, X 2 , R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 5 ′, R 6 , and R 6 ′ are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.

First claim

What is claimed is:

1. A compound of the formula:

wherein:
the bond between atom 1 and atom 2 is either a single bond or a double bond;
X 2 is CH 2 — or —O—;
R 3 , R 4 , R 3 ′, R 4 ′ are each independently hydrogen or hydroxy;
R 5 is a group of the formula:

wherein:
R 10 is halo, alkyl (C≤8) , or substituted alkyl (C≤8) ;
R 11 is halo, and
x is 0 or 1,

R 5 ′ is hydrogen;
R 6 and R 6 ′ are each independently hydrogen, alkyl (C≤12) , or substituted alkyl (C≤12) ; and
n is 1;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein X 2 is —CH 2 —.

3. The compound of claim 1 , wherein R 3 , R 3 ′, R 4 , and R 4 ′ are hydrogen.

4. The compound of claim 1 , wherein R 3 and R 4 are hydroxy.

5. The compound of claim 1 , wherein R 6 and R 6 ′ are hydrogen.

6. The compound of claim 4 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising:
(A) a compound of claim 1 ; and
(B) a pharmaceutically acceptable carrier.

8. A method of treating a neurodegenerative disease in a patient comprising administering to the patient in need thereof a therapeutically effective amount of a compound of claim 1 , wherein the neurodegenerative disease is associated with misregulation of Hsp90 or Hsp70.

9. The compound of claim 1 , wherein the bond between atom 1 and atom 2 is a single bond.

10. The compound of claim 1 , wherein R 10 is chloro.

11. The compound of claim 1 , wherein R 11 is chloro.

12. The compound of claim 1 , wherein x is 1.

13. The compound of claim 1 further defined as:

or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Kansas

Inventors

• Blagg Brian S J
• Dobrowsky Rick T
• Anyika Mercy

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title