Collect. Czech. Chem. Commun. 1994, 59, 421-428

The Deamino-Carba Analogs of Vasotocin. Synthesis and Some Biological Properties

Zdenko Procházkaa, Jiřina Slaninováa, Per Melinb, Carl-Johan Aurellb and Michal Lebla

a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
b Ferring AB, Malmö, Sweden


Solid phase methodology on benzhydrylamine resin with linkage agent and Fmoc technique was used for the synthesis of two analogs of deamino carba-1 and carba-6 oxytocin with phenylalanine in position 2 and with ornithine in position 8. The following analogs were prepared: [Phe2,Orn8]deamino-carba-1-oxytocin (I) and [Phe2,Orn8]deamino-carba-6-oxytocin (II). Moreover, analogs with δ-amino group of ornithine protected by benzyloxycarbonyl group and its corresponding sulfoxides were isolated and tested. Both deprotected analogs were found to have high uterotonic activity in vivo, and moderate pressor and antidiuretic agonistic activity. Surprisingly, in uterotonic test they are only partial agonists. The analogs with protected ornithine have preserved high uterotonic in vivo activity in contrary to the pressor activity that was strongly decreased.