Phenylpiperidine-benzoxazinones as urotensin-II receptor antagonists: synthesis, SAR, and in vivo assessment

Diane K Luci; Shyamali Ghosh; Charles E Smith; Jenson Qi; Yuanping Wang; Barbara Haertlein; Tom J Parry; Jian Li; Harold R Almond Jr; Lisa K Minor; Bruce P Damiano; William A Kinney; Bruce E Maryanoff; Edward C Lawson

doi:10.1016/j.bmcl.2007.09.092

Phenylpiperidine-benzoxazinones as urotensin-II receptor antagonists: synthesis, SAR, and in vivo assessment

Bioorg Med Chem Lett. 2007 Dec 1;17(23):6489-92. doi: 10.1016/j.bmcl.2007.09.092. Epub 2007 Oct 1.

Authors

Diane K Luci¹, Shyamali Ghosh, Charles E Smith, Jenson Qi, Yuanping Wang, Barbara Haertlein, Tom J Parry, Jian Li, Harold R Almond Jr, Lisa K Minor, Bruce P Damiano, William A Kinney, Bruce E Maryanoff, Edward C Lawson

Affiliation

¹ Research & Early Development, Johnson & Johnson Pharmaceutical Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.

PMID: 17933531
DOI: 10.1016/j.bmcl.2007.09.092

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.

Publication types

Comparative Study

MeSH terms

Animals
Benzoxazines / chemical synthesis*
Benzoxazines / pharmacology
CHO Cells
Cricetinae
Cricetulus
Humans
Piperidines / chemical synthesis*
Piperidines / pharmacology
Rats
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, G-Protein-Coupled / physiology
Structure-Activity Relationship
Urotensins / antagonists & inhibitors
Urotensins / metabolism*
Urotensins / physiology

Substances

Benzoxazines
Piperidines
Receptors, G-Protein-Coupled
UTS2R protein, human
Urotensins
4-phenylpiperidine
urotensin II