The analogs of 8-D-homoarginine-vasopressin with p-substituted phenylalanine in position 2; Synthesis and some biological properties

Abstract

Solid phase methodology on benzhydrylamine resin was used for the synthesis of five analogs of vasopressin with non-coded amino acid, D-homoarginine, in position 8 and p-substituted D or L phenylalanine in position 2. Besides the mother analog, [D-Har8]vasopressin (I), [L-Phe(Me)2, D-Har8]vasopressin (II), [D-Phe(Me)2, D-Har8]vasopressin (III), [L-Phe(Et)2, D-Har8]vasopressin (IV), [D-Phe(Et)2, D-Har8]vasopressin (V) were synthesized. All analogs have very low antidiuretic and pressor activities. Analogs containing p-ethylphenylalanine of both D and L configuration are pressor inhibitors. All analogs substituted in position 2 were found to be uterotonic inhibitors, the most potent being [D-Phe(Et)2, D-Har8]vasopressin (V) with pA2 8.15.