GnRH analogs

US5580957A · kind A · utility

Assignee

• Salk Institute for Biological Studies · US

Inventors

• Carl A. Hoeger · San Marcos, US
• Jean E. F. Rivier · Village of La Jolla, US
• Paula G. Theobald · Oceanside, US
• John S. Porter · Leucadia, US

Key dates

• Filing date: Mar 18, 1994
• Grant date: Dec 3, 1996
• Expiry date: Mar 18, 2014

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C2601/14
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Peptides which include unnatural amino acids and which either promote or 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 peptides that are GnRH antagonists prevents ovulation of female mammalian eggs and/or the release of steroids by the gonads and may be used to treat steroid-dependent tumors. The agonists can be used for control of reproduction processes, to treat precocious puberty, endometriosis, and the like. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-, 5-, 6- and/or 8-positions. Unnatural amino acids having the following formula are incorporated in a preferred group of synthesized peptides: ##STR1## Methods for synthesizing such peptides having the triazole side chains are disclosed wherein one side chain modification (or two simultaneously) is carried out on an amino-substituted phenylalanine residue in a peptide chain which is a part of a peptidoresin.