Collect. Czech. Chem. Commun. 1992, 57, 604-613

Amino and Deamino Analogs of 8-D-Homoarginin-vasopressin with Modified Tyrosine in Position 2: Synthesis and Some Biological Properties

Miroslava Žertová, Zdenko Procházka, Jiřina Slaninová, Jana Škopková, Tomislav Barth 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 seven analogs of amino or deamino vasopressin with non-coded amino acid, D-homoarginine, in position 8 and D- or L- O-methyl or O-ethyl tyrosine in position 2. [L-Tyr-(Me)2, D-Har8]vasopressin (I), [D-Tyr(Me)2, D-Har8]vasopressin (II), [L-Tyr(Et)2, D-Har8]vasopressin (III), [D-Tyr(Et)2, D-Har8]vasopressin (IV), [Mpr1, L-Tyr(Me)2, D-Har8]vasopressin (V), [Mpr1, D-Tyr(Me)2, D-Har8]vasopressin (VI) and [Mpr1, D-Tyr(Et)2, D-Har8]vasopressin (VII) were synthesized. All analogs have very low antidiuretic activity. Analogs containing O-methyltyrosine of D-configuration or O-ethyltyrosine of both D- and L-configuration are low pressor inhibitors. All analogs were found to be uterotonic inhibitors, the most potent one in vitro being [Mpr1, D-Tyr(Me)2, D-Har8]vasopressin (VI) with pA2 = 9.0 and [Mpr1, D-Tyr(Et)2, D-Har8]vasopressin (VII) with pA2 = 8.8.