Collect. Czech. Chem. Commun. 1991, 56, 1761-1767

Strong uterotonic inhibitors – analogs of 1-deamino-8-D-homoarginine-vasopressin with p-substituted phenylalanine in position 2

Miroslava Žertová, Zdenko Procházka, Tomislav Barth, Jiřina Slaninová, Jana Škopková, Ivo Bláha and Michal Lebl

Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6


Solid phase methodology on benzhydrylamine or p-methylbenzhydrylamine resin was used for the synthesis of five analogs of deamino-vasopressin with non-coded amino acids. D-homoarginine, in position 8 and p-substituted D- or L-phenylalanine in position 2. Besides the mother analog, [Mpr1, D-Har8]vasopressin (I), [Mpr1, L-Phe(p-Me)2, D-Har8]vasopressin (II), [Mpr1, D-Phe(p-Me)2,D-Har8]vasopressin (III), [Mpr1, L-Phe(p-Et)2, D-Har8]vasopressin (IV) and [Mpr1, D-Phe(p-Et)2, D-Har8]vasopressin (V) were synthesized. All analogs have very low antidiuretic and pressor activities. Analogs containing p-methylphenylalanine of L-configuration and p-ethylphenylalanine of both D- and L-configuration are pressor inhibitors. All analogs substituted in position 2 were found to act as the uterotonic inhibitors, the most potent being [Mpr1, D-Phe(p-Et)2, D-Har8]vasopressin (V) with pA2 = 8.30.