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...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 2007-12, Vol.17 (23), p.6489-6492
Hauptverfasser:	Luci, Diane K., Ghosh, Shyamali, Smith, Charles E., Qi, Jenson, Wang, Yuanping, Haertlein, Barbara, Parry, Tom J., Li, Jian, Almond, Harold R., Minor, Lisa K., Damiano, Bruce P., Kinney, William A., Maryanoff, Bruce E., Lawson, Edward C.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antagonist Benzoxazines - chemical synthesis Benzoxazines - pharmacology Biological and medical sciences CHO Cells Cricetinae Cricetulus Ear flush Humans Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Piperidine Piperidines - chemical synthesis Piperidines - pharmacology Rats Receptors, G-Protein-Coupled - antagonists & inhibitors Receptors, G-Protein-Coupled - physiology Structure-Activity Relationship Urotensin Urotensins - antagonists & inhibitors Urotensins - metabolism Urotensins - physiology
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Zusammenfassung:	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. 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.
ISSN:	0960-894X 0968-0896 1464-3405 1464-3391
DOI:	10.1016/j.bmcl.2007.09.092