Effective antagonists of the luteinizing hormone releasing hormone which release negligible histamine

US4935491A · kind A · utility

Assignees

• The Board of Regents of the University of Texas System · US
• The Administrators of the Tulane Educational Fund · US

Inventors

• Karl Folkers · Austin, US
• Anders Ljungqvist · Austin, US
• Dong-Mei Feng · Harleysville, US
• Cyril Y. Bowers · New Orleans, US
• Pui-Fun L. Tang · Sha Tin, CN
• Minoru Kubota · Austin, US

Key dates

• Filing date: Aug 24, 1987
• Grant date: Jun 19, 1990
• Expiry date: Aug 24, 2007

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S930/13
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The objective of the research was the achievement of antagonists of the luteinizing hormone releasing hormone (LHRH) which would have adequate antagonistic activity to prevent ovulation, and yet would not have a pronounced structural feature to release a histamine, in vivo. Some existing antagonists of LHRH produced edema of the face and extremities in rats. This recent recognition of the edematogenic and anaphylactoid activities of an antagonist of LHRH necessitated new structural changes if such antagonists were to be considered for potential use as contraceptive agents in the human. Consequently, 57 peptides have been designed, synthesized and bioassayed toward achieving a potent antagonist which releases negligible histamine. Since there was no predictable structural sequence which offered assurance of such achievement, it was necessary to design, synthesize and bioassay a very large number of peptides having diverse structural changes toward ultimately discovering an antagonist with the necessary potency of antiovulatory activity and the necessary negligible release of histamine. Ultimately, this objective was achieved, and this application describes the diverse and unpredicta…