Inhibitors of cellular necrosis and related methods

Patent metadata

Field	Value
Publication number	US-2016304498-A1
Application number	US-201615194413-A
Country	US
Kind code	A1
Filing date	Jun 27, 2016
Priority date	Dec 11, 2014
Publication date	Oct 20, 2016
Grant date	—

Abstract

A compound having the following structure (I):

or a pharmaceutically acceptable salt, prodrug, stereoisomer or tautomer thereof, is provided. Related compounds, methods for preparation of the same and uses of the compounds for treatment of various indications, including treatment of necrotic cell diseases and/or inflammation, are also provided.

First claim

1 . (canceled)

2 . A compound having the following structure (Ia):

or a pharmaceutically acceptable salt, prodrug or tautomer thereof.

3 - 12 . (canceled)

13 . A pharmaceutical composition comprising a compound having the following structure (Ia):

or a pharmaceutically acceptable salt, prodrug or tautomer thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

14 . A method for treating a necrotic cell disease, the method comprising administering an effective amount of a pharmaceutical composition to a subject in need thereof, wherein the pharmaceutical composition comprises a compound having the following structure (Ia):

or a pharmaceutically acceptable salt, prodrug or tautomer thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

15 . The method of claim 14 , wherein the necrotic cell disease is trauma, ischemia, stroke, cardiac infarction, infection, Gaucher's disease, Krabbe disease, sepsis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, HIV-associated dementia, retinal degenerative disease, glaucoma, age-related macular degeneration, rheumatoid arthritis, psoriasis, psoriatic arthritis or inflammatory bowel disease.

16 . A method for treating an inflammatory disorder, the method comprising administering an effective amount of the composition of claim 13 to a subject in need thereof.

17 . The method of claim 16 , wherein the inflammatory disorder is inflammatory bowel disease.

18 . The method of claim 16 , wherein the inflammatory disorder is Crohn's disease or ulcerative colitis.

19 - 54 . (canceled)

55 . The method of claim 15 , wherein the necrotic cell disease is Parkinson's disease.

56 . The method of claim 15 , wherein the necrotic cell disease is Alzheimer's disease.

57 . The method of claim 15 , wherein the necrotic cell disease is amyotrophic lateral sclerosis.

58 . The method of claim 15 , wherein the necrotic cell disease is Huntington's disease.

59 . The method of claim 15 , wherein the necrotic cell disease is HIV-associated dementia.

Assignees

• Harvard College
• Shanghai Inst Of Organic Chemistry

Inventors

• Yuan Junying
• Zhou Yijun
• Qian Shan
• Ma Dawei

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• C07D403/06 Primary

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• A61P29/00

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

• C07D233/78

  Radicals substituted by oxygen atoms · CPC title