Phenylpiperidine-benzoxazinones as urotensin-II receptor antagonists: synthesis, SAR, and in vivo assessment.
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.
Luci
Diane K
DK
Research & Early Development, Johnson & Johnson Pharmaceutical Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
Ghosh
Shyamali
S
Smith
Charles E
CE
Qi
Jenson
J
Wang
Yuanping
Y
Haertlein
Barbara
B
Parry
Tom J
TJ
Li
Jian
J
Almond
Harold R
HR
Minor
Lisa K
LK
Damiano
Bruce P
BP
Kinney
William A
WA
Maryanoff
Bruce E
BE
Lawson
Edward C
EC
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
D048588:Benzoxazines; D010880:Piperidines; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C048151:4-phenylpiperidine; C029677:urotensin II