title: Phenylpiperidine-benzoxazinones as urotensin-II receptor antagonists: synthesis, SAR, and in vivo assessment.
abstract: Various 4-phenylpiperidine-benzoxazin-3-ones were synthesized and biologically evaluated as urotensin-II (U-II) receptor antagonists. Compound 12i was identified from in vitro evaluation as a low nanomolar antagonist against both rat and human U-II receptors. This compound showed in vivo efficacy in reversing the ear-flush response induced by U-II in rats.
authors.affiliation: Research & Early Development, Johnson & Johnson Pharmaceutical Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors.forename: Diane K
authors.initials: DK
authors.lastname: Luci
authors.forename: Shyamali
authors.initials: S
authors.lastname: Ghosh
authors.forename: Charles E
authors.initials: CE
authors.lastname: Smith
authors.forename: Jenson
authors.initials: J
authors.lastname: Qi
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Wang
authors.forename: Barbara
authors.initials: B
authors.lastname: Haertlein
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Parry
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Harold R
authors.initials: HR
authors.lastname: Almond
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Minor
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Damiano
authors.forename: William A
authors.initials: WA
authors.lastname: Kinney
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Maryanoff
authors.forename: Edward C
authors.initials: EC
authors.lastname: Lawson
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000502:physiology; D013329:Structure-Activity Relationship; D014579:Urotensins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology
chemical_list: D048588:Benzoxazines; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C048151:4-phenylpiperidine; C029677:urotensin II