Macrocyclic compounds for treatment of medical disorders

Patent metadata

Field	Value
Publication number	US-12297205-B2
Application number	US-202318196002-A
Country	US
Kind code	B2
Filing date	May 11, 2023
Priority date	Mar 1, 2017
Publication date	May 13, 2025
Grant date	May 13, 2025

Abstract

Macrocyclic 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, Formula V, Formula VI, Formula VII, and Formula VIII 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

We claim:

1. A compound selected from:

or a pharmaceutically acceptable salt thereof.

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

3. A method of inhibiting complement factor D, comprising administering to a patient in need thereof an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

4. The method of claim 3 , wherein the patient is human.

5. The method of claim 3 , wherein the patient has a complement factor D disorder 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, cardiovascular disease, cold agglutinin disease, complement 3 glomerulopathy, chronic obstructive pulmonary disease, cirrhosis, Crohn's disease, C3 glomerulonephritis, diabetic retinopathy, 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, ocular disorder, ophthalmic disease, pancreatitis, paroxysmal nocturnal hemoglobinuria, pemphigoid, pemphigus vulgaris, pre-eclampsia, reduced glomerular filtration rate, renovascular disorder, 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, ulcerative colitis, and viral infection.

6. The method of claim 5 , wherein the disorder is a renovascular disorder.

7. The method of claim 5 , wherein the disorder is paroxysmal nocturnal hemoglobinuria.

8. The method of claim 5 , wherein the disorder is an ophthalmic disease.

9. The method of claim 5 , wherein the disorder is age-related macular degeneration or retinal detachment.

10. The method of claim 5 , wherein the disorder is geographic atrophy.

11. The method of claim 10 , wherein the disorder is sickle cell disease.

12. The method of claim 10 , wherein the disorder is myasthenia gravis.

13. The method of claim 5 , wherein the disorder is lupus nephritis.

14. The method of claim 5 , wherein the disorder is IgA nephropathy.

15. The method of claim 5 , wherein the disorder is a viral infection.

Assignees

• Achillion Pharmaceuticals Inc

Inventors

• Wiles Jason Allan
• Phadke Avinash S
• Chen Dawei
• Gadhachanda Venkat Rao
• Barrish Joel Charles
• Agarwal Atul
• Eastman Kyle J

Classifications

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P31/12 Primary

  Antivirals · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• C07D487/18

  Bridged systems · CPC title