Tetrahydrothiophene-based GABA Aminotransferase Inactivators and Analogs Thereof for Treating Neurological Disorders

Patent metadata

Field	Value
Publication number	US-2019256489-A1
Application number	US-201916252037-A
Country	US
Kind code	A1
Filing date	Jan 18, 2019
Priority date	Mar 9, 2015
Publication date	Aug 22, 2019
Grant date	—

Abstract

Tetrahydrothiophene and related heterocyclic analogs and related methods for GABA aminotransferase inactivation.

First claim

1 .- 20 . (canceled)

21 . A method for treating a neurological disorder characterized by gamma-aminobutyric acid (GABA) amino transferase (AT) activity in a subject in need thereof, the method comprising administering to the subject a compound of a formula:

wherein X is selected from S, SO 2 , CH 2 , O, and NR, where R is selected from H and straight and branched C1-C6 alkyl moieties, or a salt thereof.

22 . The method of claim 21 , wherein the neurological disorder is epilepsy.

23 . The method of claim 21 , wherein in the compound X is S.

24 . The method of claim 23 , wherein the compound is of a formula:

25 . The method of claim 24 , wherein in the compound the amino substituent and the carboxy substituent have a cis stereochemical relationship.

26 . The method of claim 21 , wherein the compound is an ammonium salt.

27 . The method of claim 26 , wherein the counter ion of the ammonium salt is a conjugate base of a protic acid.

28 . A method for treating a neurological disorder characterized by gamma-aminobutyric acid (GABA) amino transferase (AT) activity in a subject in need thereof, the method comprising administering to the subject a compound of a formula:

or a salt thereof.

29 . The method of claim 28 , wherein the neurological disorder is epilepsy.

30 . The method of claim 28 , wherein the compound is of a formula:

31 . The method of claim 30 , wherein the compound is a salt comprising an ammonio substituent, a carboxylate substituent or a combination thereof.

32 . The method of claim 31 , wherein the compound is an ammonium salt.

33 . The method of claim 32 , wherein the counter ion of the ammonium salt is a conjugate base of a protic acid.

Assignees

• Univ Northwestern

Inventors

• Silverman Richard B
• Le Hoang V
• Hawker Dustin D

Classifications

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C12N9/1096

  transferring nitrogenous groups (2.6) · CPC title

• C12N9/99

  Enzyme inactivation by chemical treatment · CPC title

• C12Y206/01019

  4-Aminobutyrate—2-oxoglutarate transaminase (2.6.1.19) · CPC title