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Published on: December 26, 2011
Nanomolar-affinity, non-peptide oxytocin receptor antagonists
B E Evans1, G F Lundell, K F Gilbert
1Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486.
Abstract:
Non-peptide antagonists 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.
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