Potent and Selective Oxytocin Antagonists Obtained by Chemical Modification of a Streptomyces Silvensis Derived Cyclic Hexapeptide and by Total Synthesis

Oxytocin (OT) is a neurohypophyseal hormone which has an important function in parturition.1 There is considerable evidence that the uterotonic action of OT and its stimulation of uterine prostaglandin release combine to initiate labor.2,3 Additionally, OT mediates the postpartum function of contracting the mammary myoepithelium to elicit milk letdown4 and has also recently been implicated as a key element in preterm labor.5,6 Attempts to further delineate these OT connected events have provided the impetus to discover agents which interact selectively and competitively at the OT receptor. Such compounds are invaluable in determining the physiological and pathophysiological role of OT and its close structurally related hormone, arginine vasopressin (AVP). Additional interest derives from the prospect of their use as novel therapeutic agents.