ANTAGONISTIC ANALOGS OF OXYTOCIN WITH SUBSTITUTED PHENYLALANINE OR TYROSINE IN POSITION-2

Solid phase method on p-methylbenzhydrylamine resin was used for the s ynthesis of seven analogs of oxytocin with non-coded amino acids in po sition 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]oxy tocin (VII) were synthesized. All analogs with D-stereoisomer of alkyl or alkoxy substituted phenylalanine possess uterus in vitro inhibitin g activity. In the case of L-stereoisomers the structure-activity rela tionship is more complicated. As far as the pressor activity is concer ned. the analogs have either very low agonistic activity or low degree of antagonism.