Biaryl amides with modified sugar groups for treatment of diseases associated with heat shock protein pathway

Patent metadata

Field	Value
Publication number	US-11827664-B2
Application number	US-201917055331-A
Country	US
Kind code	B2
Filing date	May 14, 2019
Priority date	May 14, 2018
Publication date	Nov 28, 2023
Grant date	Nov 28, 2023

Abstract

Provided are biaryl amides and coumarin-based compounds with modified sugar groups for treatment of diseases associated with heat shock protein pathway. The compounds having the following formulas, wherein variables are as defined herein. Formulae (I), (II), (III), (IV), and (V), Pharmaceutical compositions of the compounds are also provided. These biaryl amides and coumarin-based derivatives with modified sugar groups are useful for treatment and prevention of diseases and disorders, including neurological disorders, such as neurodegenerative diseases and nerve damaging disorders, for example, diabetic peripheral neuropathy.

First claim

What is claimed is:

1. A compound of the formula:

wherein:
n is 1;
Y 1 is -alkanediyl (C≤6) -, —C(O)-alkanediyl (C≤6) -, or a substituted version of any of these groups;
Y 2 is O;
R 3 is —NR 11 R 11 ′ or —C(O)NR 12 R 12 ′, wherein:
R 11 and R 11 ′ are each independently hydrogen, alkyl (C≤6) , substituted alkyl (C≤6) , acyl (C≤6) , or substituted acyl (C≤6) ;
R 12 and R 12 ′ are each independently hydrogen, alkyl (C≤6) , or substituted alkyl (C≤6) ;

R 7 is alkyl (C≤6) or substituted alkyl (C≤6) ;
R 8 is hydroxy, alkoxy (C≤6) , or substituted alkoxy (C≤6) ; and
R 9 and R 10 are each hydroxy;

or a pharmaceutically acceptable salt of the formula.

2. The compound of claim 1 further defined as:

wherein:
n is 1;
R 7 is alkyl (C≤6) substituted alkyl (C≤6) ;
R 8 is hydroxy alkoxy (C≤6) , or substituted alkoxy (C≤6) ; and
R 9 and R 10 are each hydroxy;

or a pharmaceutically acceptable salt of the formula.

3. The compound of claim 1 , wherein Y 1 is -alkanediyl (C≤6) - or substituted -alkanediyl (C≤6) - and R 3 is —R 11 R 11 ′.

4. The compound of claim 1 , wherein R 8 is hydroxy.

5. The compound of claim 1 , wherein R 7 is alkyl (C≤6) .

6. A pharmaceutical composition comprising:
(A) a compound of claim 1 ; and
(B) an excipient.

7. The compound of claim 2 further defined as:

wherein:
R 7 is alkyl (C≤6) ; and
R 8 is hydroxy, alkoxy (C≤6) , or substituted alkoxy (C≤6) ;

or a pharmaceutically acceptable salt of the formula.

8. The compound of claim 7 further defined as:

wherein:
R 7 is alkyl (C≤6) ; and
R 8 is hydroxy or alkoxy (C≤6) ;

or a pharmaceutically acceptable salt of the formula.

9. The compound of claim 8 further defined as:

wherein:
R 7 is alkyl (C≤6) ; and
R 8 is hydroxy;

or a pharmaceutically acceptable salt of the formula.

10. The compound of claim 1 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt of any of these formulas.

11. The compound of claim 10 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt of any of these formulas.

12. The compound of claim 11 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt of any of these formulas.

13. The compound of claim 12 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 , wherein R 8 is alkoxy (C≤6) .

15. The compound of claim 12 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 , wherein R 7 is substituted alkyl (C≤6) , wherein the alkyl (C≤6) is substituted with an OH, OCH 3 , F, Cl, or Br group.

17. The compound of claim 16 , wherein R 7 is substituted alkyl (C≤6) , wherein the alkyl (C≤6) is substituted with an OH group.

Assignees

• Reata Pharmaceuticals Inc

Inventors

• Jiang Xin
• Visnick Melean
• Bender Christopher F
• Bolton Gary
• CAPRATHE Bradley
• Lee Chitase

Classifications

• C07C2601/14

  The ring being saturated · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P3/10 Primary

  for hyperglycaemia, e.g. antidiabetics · CPC title