Collect. Czech. Chem. Commun. 1994, 59, 1430-1438

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

Rudolf Ježek, Miroslava Žertová, Jiřina Slaninová, Pavel Majer and Zdenko Procházka

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic


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.