Using adiponectin receptor agonists to treat inflammation and bone diseases in diabetes

Patent metadata

Field	Value
Publication number	US-11655212-B2
Application number	US-202117550834-A
Country	US
Kind code	B2
Filing date	Dec 14, 2021
Priority date	Dec 14, 2020
Publication date	May 23, 2023
Grant date	May 23, 2023

Abstract

Disclosed herein are adiponectin receptor agonists and methods of using the same for the treatment of inflammation or bone loss in a subject.

First claim

We claim:

1. A compound of formula

or a pharmaceutically acceptable salt thereof,
wherein R 1 is —C(═O)R 4 ; R 4 is a halo-substituted phenyl, an unsubstituted phenyl, or a C 1 -C 4 alkyl; R 2 is a C 1 -C 4 alkoxyl, hydrogen, or a halo; and R 3 is hydrogen or a C 1 -C 4 alkyl; or
wherein R 1 is an unsubstituted phenyl; R 2 is a C 1 -C 4 alkoxyl or hydrogen; and R 3 is hydrogen or a C 1 -C 4 alkyl; and
wherein
if R 1 is —C(═O)R 4 and R 4 is a 4-chloro substituted phenyl, R 2 and R 3 are not both hydrogen;
if R 1 is —C(═O)R 4 and R 4 is the unsubstituted phenyl, (i) R 2 and R 3 are not both hydrogen or (ii) R 2 and R 3 are not respectively 4-chloro and hydrogen;
if R 1 is —C(═O)R 4 and R 4 is methyl, R 2 and R 3 are not respectively 3,4-dichloro and hydrogen, 3,4-dichloro and hydrogen, or 4-bromo and hydrogen;
if R 1 is —C(═O)R 4 and R 4 is ethyl, R 2 and R 3 are not respectively 3,4-dichloro and hydrogen; and
if R 1 is phenyl, R 2 and R 3 are not respectively hydrogen and methyl.

2. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the compound is

4. The compound of claim 1 , wherein the compound is

5. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable excipient, carrier, or diluent.

6. A method for the treatment of inflammation a subject, the method comprising administering an effective amount of the compound according to claim 1 .

7. The method of claim 6 , wherein the subject has chronic inflammation.

8. The method of claim 6 , wherein the subject has diabetes.

9. The method of claim 6 , wherein the subject is obese.

10. The method of claim 6 , wherein the subject has an infection.

11. The method of claim 10 , wherein the subject suffers from sepsis, septic shock, or endotoxemia.

12. The method of claim 6 , wherein administering the effective amount of the compound decreases fasting blood glucose in the subject.

13. The method of claim 6 , wherein administering the effective amount of the compound inhibits or reduces expression of a proinflammatory cytokine in the subject.

14. The method of claim 6 , wherein administering the effective amount of the compound increases expression of an anti-inflammatory cytokine in the subject.

15. The method of claim 6 , wherein the compound is

16. A method for the treatment of bone loss a subject, the method comprising administering an effective amount of the compound according to claim 1 .

17. The method of claim 16 , wherein the subject has periodontitis.

18. The method of claim 16 , wherein the subject has type 2 diabetes (T2D)-associated periodontitis.

19. The method of claim 16 , wherein administering the effective amount of the compound increases autophagy in osteoclasts.

20. The method of claim 16 , wherein the compound is

Assignees

• Tufts College

Inventors

• Chen Jinkun
• Tu Qisheng
• Wu Xingwen
• Chen Gang
• Qiu Wei

Classifications

• C07D211/58 Primary

  attached in position 4 · CPC title

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61P29/00

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