PEPTIDO-MIMETIC COMPOUNDS CONTAINING RGD SEQUENCE USEFUL AS INTEGRIN INHIBITORS

摘要

A cyclic peptide compound having an RGD(Arg-Gly-Asp) sequence is provided to inhibit activity of integrin alphavbeta3-receptor, thereby being useful as a therapeutic agent for treating an altered angiogenesis such as tumors. A cyclic peptide compound is represented by the formula(1), wherein n is 0,1 or 2, and Arg is the amino acid L-Arginine, Gly is the amino acid Glycine and Asp is the amino acid L-Aspartic acid. A method for preparing the compound comprises the steps of: (a) subjecting a compound of the formula(2) to Horner-Emmons olefination(wherein R is a lower allyl residue and R1 is a suitable nitrogen protecting group) to obtain a compound of the formula(3)(wherein R3 is a suitable nitrogen protecting group and R4 is a lower alkyl residue); (b) hydrogenating the compound of the formula(3) and cyclizing it; and if desired (c) separating the stereoisomeric mixture; (d) building the RGD cyclic sequence; and if desired (e) separating the stereoisomeric compound.