Antagonistic Analogs of Oxytocin with Substituted Phenylalanine or Tyrosine in Position 2

Abstract

Solid phase method on p-methylbenzhydrylamine resin was used for the synthesis of seven analogs of oxytocin with non-coded amino acids in position 2. [L-Phe(4-Me) 2 ]oxytocin ( I ), [D-Phe(4-Me) 2 ]oxytocin ( II ), [L-Phe(2-Me,4-Et) 2 ]oxytocin ( III ), [D-Phe(2-Me,4-Et) 2 ]oxytocin ( IV ), [D-Tyr(Me) 2 ]oxytocin ( V ), [D-Tyr(Et) 2 ]oxytocin ( VI ) and [L-Tyr(2-Me) 2 ]oxytocin ( VII ) were synthesized. All analogs with D-stereoisomer of alkyl or alkoxy substituted phenylalanine possess uterus in vitro inhibiting activity. In the case of L-stereoisomers the structure activity relationship is more complicated. As far as the pressor activity is concerned, the analogs have either very low agonistic activity or low degree of antagonism.