Pharmaceutical compounds for treatment of medical disorders

Patent metadata

Field	Value
Publication number	US-12006307-B2
Application number	US-202217872104-A
Country	US
Kind code	B2
Filing date	Jul 25, 2022
Priority date	Mar 1, 2017
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

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, and Formula IV 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 of structure:

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 treating a disorder mediated by complement Factor D, the method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

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

5. The method of claim 3 , 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.

6. The method of claim 5 , wherein the disorder is age-related macular degeneration, C3 glomerulonephritis, dense deposit disease, geographic atrophy, IgA nephropathy, lupus nephritis, myasthenia gravis, paroxysmal nocturnal hemoglobinuria, reduced glomerular filtration rate, a renovascular disorder, or sickle cell disease.

7. A compound of structure:

or a pharmaceutically acceptable salt thereof.

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

• C07F9/65583

  each of the hetero rings containing nitrogen as ring hetero atom · CPC title

• C07D513/04

  Ortho-condensed systems · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• C07D493/04

  Ortho-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title