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

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-Har 8 ]vasopressin ( I ), [D-Tyr(Me) 2 , D-Har 8 ]vasopressin ( II ), [L-Tyr(Et) 2 , D-Har 8 ]vasopressin ( III ), [D-Tyr(Et) 2 , D-Har 8 ]vasopressin ( IV ), [Mpr 1 , L-Tyr(Me) 2 , D-Har 8 ]vasopressin ( V ), [Mpr 1 , D-Tyr(Me) 2 , D-Har 8 ]vasopressin ( VI ) and [Mpr 1 , D-Tyr(Et) 2 , D-Har 8 ]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 [Mpr 1 , D-Tyr(Me) 2 , D-Har 8 ]vasopressin ( VI ) with p A 2 = 9.0 and [Mpr 1 , D-Tyr(Et) 2 , D-Har 8 ]vasopressin ( VII ) with p A 2 = 8.8.