Aryl, heteroaryl, and heterocyclic pharmaceutical compounds for treatment of medical disorders

Patent metadata

Field	Value
Publication number	US-11708351-B2
Application number	US-202117366670-A
Country	US
Kind code	B2
Filing date	Jul 2, 2021
Priority date	Mar 1, 2017
Publication date	Jul 25, 2023
Grant date	Jul 25, 2023

Abstract

Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, and Formula V, or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.

First claim

What is claimed is:

1. A method of treating a disorder mediated by complement cascade Factor D, the method comprising administering to a subject ion need thereof an effective amount of a compound selected from:

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the subject is a human.

8. The method of claim 1 , wherein the disorder is selected from acute respiratory distress syndrome, age-related macular degeneration, arthritis, asthma, Alzheimer's dementia, amyotrophic lateral sclerosis, antibody-mediated transplant rejection, antineutrophil cytoplasm antibody-associated vasculitis, antiphospholipid syndrome, atypical or typical hemolytic uremic syndrome, a cardiovascular disease, cold agglutinin disease, chronic obstructive pulmonary disease, cirrhosis, Crohn's disease, C3 glomerulonephritis, diabetic retinopathy, dense deposit disease, dermatomyositis, dermatitis, epidermolysis bullosa acquisita, fatty liver, focal segmental glomerulosclerosis, geographic atrophy, glomerulonephritis, graft versus host disease, Guillain Barre syndrome, hemolytic anemia, hidradenitis suppurativa, IgA nephropathy, ischemia/reperfusion injury, liver failure, liver inflammation, lupus nephritis, membrane proliferative glomerulonephritis, multifocal motor neuropathy, multiple sclerosis, myasthenia gravis, neuromyelitis optica, nonalcoholic steatohepatitis (NASH), an ophthalmic disease, pancreatitis, paroxysmal nocturnal hemoglobinuria, pemphigoid, pemphigus vulgaris, pre-eclampsia, reduced glomerular filtration rate, a renovascular disorder, a respiratory disease, retinal detachment, rheumatoid arthritis, scleroderma, sepsis, shiga toxin E. coli -related hemolytic uremic syndrome, spinal cord injury, sickle cell disease, traumatic brain injury, and ulcerative colitis.

9. The method of claim 8 , wherein the disorder is IgA nephropathy.

10. The method of claim 8 , wherein the disorder is geographic atrophy.

11. The method of claim 8 , wherein the disorder is lupus nephritis.

12. The method of claim 8 , wherein the disorder is myasthenia gravis.

13. The method of claim 8 , wherein the disorder is reduced glomerular filtration rate.

14. The method of claim 8 , wherein the disorder is renovascular disorder.

15. The method of claim 8 , wherein the disorder is sickle cell disease.

16. The method of claim 8 , wherein the disorder is C3 glomerulonephritis.

17. The method of claim 8 , wherein the disorder is dense deposit disease.

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
• Barrish Joel Charles
• Greenlee William
• Eastman Kyle J

Classifications

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07D403/14 Primary

  containing three or more hetero rings · CPC title

• C07D409/14

  containing three or more hetero rings · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D471/08

  Bridged systems · CPC title