Recent Advances in the Development of Oxytocin Receptor Antagonists

Abstract

Abstract: During the last decade there has been significant progress in the design and discovery of new structural classes of oxytocin antagonists. Continued study of oxytocin analogs has led to the design of antagonists. The similar topography of important functionalities in peptide and non-peptide oxytocin antagonists suggest the possibility of a common pharmacophore. New modifications to the classical antagonist analogs of oxytocin have provided analogs with significant improvements in potency, dura- tion of action, oxytocin receptor selectivity, and bioavailability by non-parenteral routes of administration. In addition, optimization within two structural classes of non-peptides has provided potent and selective analogs which offer the potential for obtaining a clinically useful, orally bioavailable oxytocin antagonist. Human clinical studies with the peptidic oxytocin antagonist, atosiban, have implicated oxytocin as a potential contributor to the pathophysiology of preterm labor and suggests that oxytocin receptor blockade may offer a useful new method for preventing premature birth.