Derivatives of glycinergic R(+)-2-amino-3-hydroxypropanoic acid

• US 7,488,755 B2
• Filed: 08/01/2003
• Issued: 02/10/2009
• Est. Priority Date: 08/14/2002
• Status: Expired due to Fees

• Current Assignee: Prestwick Pharmaceuticals, Inc. (Bausch Health Cos., Inc.)
• Original Assignee: Prestwick Pharmaceuticals, Inc. (Bausch Health Cos., Inc.)
• Inventors: Contreras, Jean-Marie Georges, Clarence-Smith, Kathleen, Deyon, Laurence Nathalie, Wermuth, Camille Georges
• Primary Examiner(s): Padmanabhan; Sreeni
• Assistant Examiner(s): JEAN-LOUIS, SAMIRA JM
• Application Number:
  US10/524,869
• Publication Number:
  US 20050261372A1
• Time in Patent Office: 2,020 Days
• Field of Search: None
• US Class Current: 514/561
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 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 Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 2601/02 with a three-membered ring

Abstract

The use of R(+)-2-amino-3-hydroxypropanoic acid derivatives, nitrogen substituted by a (C₁-C₆)alkyl, (C₃-C₆)alkenyl, 3-oxo(C₅-C₆)alkyl, 3-oxo(C₄-C₆)alken-2-yl, phenyl(C₁-C₆)alkyl, phenyl(C₂-C₆)alkenyl, gem-diphenyl(C₁-C₆)alkyl, gem-diphenyl(C₂-C₆)alkenyl, (C₁-C₆)alcanoyl, optionally N-substituted alanyl, optionally N,N′-disubstituted lysinoyl, phenyl(C₁-C₆)alkylydene or gem-diphenyl(C₁-C₆)alkylidene group, and of the pharmaceutically acceptable salts thereof, for preparation of medicaments intended for the treatment of CNS diseases due to reduced glycinergic transmission, particularly for the treatment of autism, schizophrenia and Alzheimer'"'"'s disease, is described.

Claims

1. A R(+)-2-amino-3-hydroxypropanoic acid derivative of formula III, or one of its pharmaceutically acceptable salts;

2. The R(+)-2-amino-3-hydroxypropanoic acid derivative according to claim 1, where R′

is a ω

-diphenyl(C₂-C₆)alkyl group.

6. A method for treating schizophrenia, comprising administering to a patient the R(+)-2-amino-3-hydroxypropanoic acid derivative according to claim 1.

7. The method according to claim 6, wherein said treatment increases glycinergic transmission in said patient.

8. The R(+)-2-amino-3-hydroxypropanoic acid derivative according to claim 1, wherein R′

is a phenyl(C₂-C₆)alkenyl.

9. The R(+)-2-amino-3-hydroxypropanoic acid derivative according to claim 1, which is R(+)-N-(4,4-diphenyl)butyl-2-amino-3-hydroxypropanoic acid hydrochloride.

10. The R(+)-2-amino-3-hydroxypropanoic acid derivative according to claim 1, which is methyl R(+)-N-[(4,4-diphenyl)-3-butenyl]-2-amino-3-hydroxypropanoate.

11. A pharmaceutical composition comprising a pharmaceutically effective dose of the R(+)-2-amino-3-hydroxypropanoic acid derivative according to claim 1, or one of its pharmaceutically acceptable salts, in admixture with a pharmaceutically acceptable carrier.

3. R(+)-N-(4,4-diphenyl)butyl-2-amino-3-hydroxypropanoic acid or a pharmaceutically acceptable salt thereof.

4. R(+)-N-[(4,4-diphenyl)-3-butenyl]-2-amino-3-hydroxypropanoic acid or a pharmaceutically acceptable salt thereof.

5. R(+)-N-[α

-phenyl-(2-hydroxy)benzylidene]-2-amino-3-hydroxypropanoic acid or a pharmaceutically acceptable salt thereof.