作为尿紧张素II受体拮抗剂的苯基哌啶-苯并恶嗪酮：合成、构效关系及体内评估

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

作者信息

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

机构信息

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

出版信息

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

DOI:10.1016/j.bmcl.2007.09.092

PMID:17933531

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.

摘要

合成了多种4-苯基哌啶-苯并恶嗪-3-酮，并作为尾加压素-II（U-II）受体拮抗剂进行了生物学评价。化合物12i在体外评价中被鉴定为对大鼠和人U-II受体均具有低纳摩尔级别的拮抗剂。该化合物在逆转U-II诱导的大鼠耳部潮红反应方面显示出体内疗效。