Collect. Czech. Chem. Commun. 1984, 49, 2012-2023

Synthesis and properties of carba-6-analogues of oxytocin containing a deaminopenicillamine residue in position 1

Michal Lebl, Tomislav Barth, Linda Servítová, Jiřina Slaninová and Pavel Hrbas

Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6


A study was made of the influence of the so-called carba substitution of the disulphide bridge on the properties of inhibitors obtained by the introduction of deaminopenicillamine into position 1 of the oxytocin molecule. Two analogues - [dPen1]carba-6-oxytocin (Ia) and [dPen1, Tyr(Me)2]carba-6-oxytocin (Ib) were prepared and their biological activities were assayed. Compound Ia is a strong agonist in the uterotonic assay in vivo (280 I.U./mg) and a weak antagonistin the pressor assay. Compound Ib inhibited the utertonic activity of oxytocin in vitro (pA2 = 8.43) and in vivo (pA2 = 7.13) as well as the pressor action of lysine vasopressin (pA2 = 7.43).