GnRH analogs

US5169932A · 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
• Catherine L. Rivier · Village of La Jolla, US
• Wylie W. Vale, Jr. · Village of La Jolla, US

Key dates

• Filing date: Jun 27, 1990
• Grant date: Dec 8, 1992
• Expiry date: Jun 27, 2010

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S930/11
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Peptides which include unnatural amino acides and which either inhibit or promote 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. The antagonists may be used to treat steroid-dependent tumors, such as prostatic and mammary tumors. The peptides are analogs of the decapeptide GnRH wherein there is at least one residue of an unnatural amino acid in the 3-position, the 5-position, the 6-position and/or the 8-position. Such unnatural amino acids are useful in the synthesis of peptides and have the formula U*: ##STR1## where n is an integer from 1 to 6; Y is N--CN, N--CONHR.sub.9, S, O or CH--NO.sub.2 ; R.sub.9 is H, Ac, lower alkyl, aromatic or heterocyclic; X is NH, O, S, M.sub.1 (CH.sub.q).sub.p M.sub.2 or M.sub.1 --(CH.sub.2).sub.p' --M.sub.2 (CH.sub.2).sub.p" --M.sub.3, where M.sub.1 is NR.sub.10, O, S or CHR.sub.3 wherein R.sub.3 is methyl, ethyl, propyl, phenyl, pyridinyl, pyrimidinyl or purinyl, q is 1 or 2; p, p' and p" are integers between O and 6; R.sub…