title: Nanomolar-affinity, non-peptide oxytocin receptor antagonists.
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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: B E
authors.initials: BE
authors.lastname: Evans
authors.forename: G F
authors.initials: GF
authors.lastname: Lundell
authors.forename: K F
authors.initials: KF
authors.lastname: Gilbert
authors.forename: M G
authors.initials: MG
authors.lastname: Bock
authors.forename: K E
authors.initials: KE
authors.lastname: Rittle
authors.forename: L A
authors.initials: LA
authors.lastname: Carroll
authors.forename: P D
authors.initials: PD
authors.lastname: Williams
authors.forename: J M
authors.initials: JM
authors.lastname: Pawluczyk
authors.forename: J L
authors.initials: JL
authors.lastname: Leighton
authors.forename: M B
authors.initials: MB
authors.lastname: Young
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D005260:Female; D010121:Oxytocin / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010879:Piperazines; D010880:Piperidines; D018045:Receptors, Oxytocin; D013141:Spiro Compounds; C077566:L 366509; D010121:Oxytocin