Cyclic GnRH antagonists

US5064939A · kind A · utility

Assignee

• Salk Institute for Biological Studies · US

Inventors

• Jean E. F. Rivier · Village of La Jolla, US
• Steven C. Koerber · Encinitas, US
• Arnold T. Hagler · San Diego, US
• Catherine L. Rivier · Village of La Jolla, US
• Wylie W. Vale, Jr. · Village of La Jolla, US

Key dates

• Filing date: Feb 6, 1990
• Grant date: Nov 12, 1991
• Expiry date: Feb 6, 2010

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Peptides which inhibit the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. Administration of an effective amount of such GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads. These peptides may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides include cyclic, bicyclic and tricyclic analogs of the decapeptide GnRH, and preferably there are at least two covalent bonds between the residues in the 4- and 10-positions, the residues in the 5- and 8-positions and the residues in the 1- and 3-positions, respectively. Examples of such bonds include a disulfide linkage between Cys residues, an amide linkage between a side chain amino group and a side chain carboyxl group, a dicarba linkage between side-chain alkyl groups, and a carba linkage between a side-chain alkyl group and a side-chain sulfhydryl group.