Analogs of Deamino Carba Oxytocin with Inhibitory Properties; Synthesis and Biological Activities

Abstract

Solid phase methodology on polyamide-kieselguhr resin was used for the synthesis of six analogs of deamino carba-1 or carba-6 oxytocin with non-coded amino acids in position 2, threonine in position 4, ornithine in position 8 and without glycine in position 9. The following analogs were prepared: des-Gly9-[L-Phe(p-Et)2, Thr4, Orn8]deamino-carba-1-oxytocin (I), des-Gly9-[D-Phe(p-Et)2, Thr4, Orn8]deamino-carba-1-oxytocin (II), des-Gly9-[D-Tyr(Et)2, Thr4, Orn8]deamino-carba-1-oxytocin (III), des-Gly9-[L-Phe(p-Et)2, Thr4, Orn8]deamino-carba-6-oxytocin (IV), des-Gly9-[D-Phe(p-Et)2, Thr4, Orn8]deamino-carba-6-oxytocin (V), and des-Gly9-[D-Tyr(Et)2, Thr4, Orn8]deamino-carba-1-oxytocin (VI). All the analogs were found to be strong uterotonic and pressor inhibitors. The highest potency in the uterotonic inhibitory test was exhibited by analog II (pA2 = 8.3) and strongest pressor inhibitor was compound I (pA2 = 7.5).