Aryl, heteroaryl, and heterocyclic compounds for treatment of immune and inflammatory disorders

Patent metadata

Field	Value
Publication number	US-12338230-B2
Application number	US-202418418560-A
Country	US
Kind code	B2
Filing date	Jan 22, 2024
Priority date	Aug 26, 2015
Publication date	Jun 24, 2025
Grant date	Jun 24, 2025

Abstract

Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I″ and I′″ or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade. The inhibitors of Factor D described herein reduces the excessive activation of complement.

First claim

We claim:

1. A compound selected from:

or a pharmaceutically acceptable salt thereof.

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:

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein the compound is:

or a pharmaceutically acceptable salt thereof.

8. A method for the treatment of a disorder mediated by complement factor D, comprising administering an effective amount of a compound of claim 1 to a host in need thereof, wherein the disorder is selected from the group consisting of fatty liver, nonalcoholic steatohepatitis (NASH), liver inflammation, cirrhosis, liver failure, dermatomyositis, amyotrophic lateral sclerosis, cytokine or inflammatory reactions in response to biotherapeutics, an inflammatory reaction to CAR T-cell therapy, paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulonephritis, rheumatoid arthritis, multiple sclerosis, age-related macular degeneration (AMD), retinal degeneration, an ophthalmic disease, a respiratory disease, and a cardiovascular disease.

9. The method of claim 8 , wherein the host is a human.

10. The method of claim 9 , wherein the disorder is NASH.

11. The method of claim 9 , wherein the disorder is fatty liver.

12. The method of claim 9 , wherein the disorder is cirrhosis.

13. The method of claim 9 , wherein the disorder is liver failure.

14. The method of claim 9 , wherein the disorder is amyotrophic lateral sclerosis.

15. The method of claim 9 , wherein the disorder is cytokine or inflammatory reactions in response to a pharmaceutical or biotherapeutic, or an inflammatory reaction to CAR T-cell therapy.

16. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignees

• Achillion Pharmaceuticals Inc

Inventors

• Wiles Jason Allan
• Phadke Avinash S
• Deshpande Milind
• Agarwal Atul
• Chen Dawei
• Gadhachanda Venkat Rao
• Hashimoto Akihiro
• Pais Godwin
• Wang Qiuping
• Wang Xiangzhu
• Greenlee William

Classifications

• C07D493/04

  Ortho-condensed systems · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61P29/00

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

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title