Nanomolar-Affinity, Non-Peptide Oxytocin Receptor Antagonists

Article abstract of DOI:10.1021/jm00077a002

Non-peptide antagonsts of the peptide hormone oxytocin (OT) with nanomolar OT receptor affinities are described.These compounds incorporate novel amido- and amidoalkylcamphor variations to the lead structure L-366,509 (1) to achieve receptor affinity enhancements of 2-3 orders of magnitude over that compound.The new OT antagonist L-367,773 (35) is shown to be an orally bioavailable agent with good duration in vivo and to inhibit OT-stimulated uterine contractions effectively in several in vitro and in vivo models.