Use of a Glycine B partial agonist as an antipsychotic

• US 5,187,171 A
• Filed: 01/09/1989
• Issued: 02/16/1993
• Est. Priority Date: 01/09/1989
• Status: Expired due to Term

• Current Assignee: GD Searle LLC (Pfizer Inc.)
• Original Assignee: GD Searle LLC (Pfizer Inc.)
• Inventors: Cordi, Alex A.
• Primary Examiner(s): Friedman, S. J.
• Application Number:
  US07/294,851
• Time in Patent Office: 1,499 Days
• Field of Search: 514/378, 514/359
• US Class Current: 514/359
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

A class of Glycine B partial agonists is described for use for treatment of psychosis. Preferred Glycine B partial agonists include amino-isoxazolidone compounds such as D-cycloserine and its prodrugs.

Claims

1. A method to treat a psychotic disorder by administering to a subject susceptible to or suffering from a psychotic disorder a therapeutically-effective amount of a Glycine B partial agonist or a prodrug thereof selected from the family of compounds of the formula ##STR9## wherein R¹ is selected from hydrido, alkyl, haloalkyl, alkoxyalkyl, cycloalkyl, aralkyl and aryl;

wherein R² is selected from hydrido, alkyl, aralkyl, aryl, ##STR10## wherein R¹ and R² which are attached to the same nitrogen atom may be taken together to form a Schiff-base derived group selected from derivatives of aldehydes and ketones;

wherein R³ is selected from hydrido, alkyl, haloalkyl, alkoxy, alkoxyalkyl, cycloalkyl, aralkyl and aryl;

or a pharmaceutically-acceptable salt thereof.

2. The method of claim 1 wherein R¹ is selected from hydrido, lower alkyl, haloalkyl, cycloalkyl, alkoxyalkyl, phenalkyl and phenyl;

wherein R² is selected from hydrido, lower alkyl, phenalkyl, phenyl, ##STR11## wherein the Schiff-base derived group is derived from acetylacetone, salicylaldehyde, benzophenone derivatives and acetylacetic acid esters; and

wherein R³ is selected from hydrido, lower alkyl and benzyl.

3. The method of claim 2 wherein R¹ is hydrido;

wherein R² is selected from ##STR12## wherein the Schiff-base derived group is selected from ##STR13## wherein each of X and Y is independently one or more groups selected from hydrido, lower alkyl and halo; and

wherein R³ is selected from hydrido, lower alkyl and phenyl.

4. The method of claim 3 wherein R¹ is selected from hydrido and the Schiff-base derived groups ##STR14## wherein each of X and Y is independently selected from fluoro, chloro and bromo;

and wherein each of R² and R³ is hydrido.

5. The method of claim 4 said compound is D-4-amino-3-isoxazolidone.

6. The method of claim 1 wherein said compound is an optically-active isomer in the D-configuration.

7. The method of claim 1 wherein said psychotic disorder is a schizophrenic disorder.

8. The method of claim 7 wherein said schizophrenic disorder is a PCP-induced schizophrenic disorder.