2. Academic Validation
  3. Nanomolar-affinity, non-peptide oxytocin receptor antagonists

Nanomolar-affinity, non-peptide oxytocin receptor antagonists

  • J Med Chem. 1993 Dec 10;36(25):3993-4005. doi: 10.1021/jm00077a002.
B E Evans 1,  G F Lundell,  K F Gilbert,  M G Bock,  K E Rittle,  L A Carroll,  P D Williams,  J M Pawluczyk,  J L Leighton,  M B Young
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486.
PMID: 8258821 DOI: 10.1021/jm00077a002
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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