Preparation of phenylalanine derivatives bearing a 1,2,4-triazole moiety and their use in peptides

摘要

Methods of making unnatural amino acids are provided which unnatural amino acids can be incorporated into peptides which either inhibit or promote the secretion of gonadotropins by the pituitary gland and inhibit the release of steroids by the gonads. These unnatural amino acids are useful in the synthesis of peptides and have the formula (a): <IMAGE> where W is (CH2)n or <IMAGE> n is an integer from 1 to 6; j=1, 2 or 3, and preferably, Y is N-CN, X is NH and R2 is alkyl, modified alkyl, alkenyl, alkynyl, aryl or methyl pyridyl. Disclosed are peptides that 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.