平衡型AT1/AT2受体拮抗剂。4. XR510及相关的对AT1和AT2受体具有同等亲和力的5-(3-氨丙酰基)咪唑。

Balanced AT1/AT2 receptor antagonists. 4. XR510 and related 5-(3-amidopropanoyl)imidazoles possessing equal affinity for the AT1 and AT2 receptors.

作者信息

Quan M L, Chiu A T, Ellis C D, Wong P C, Wexler R R, Timmermans P B

机构信息

DuPont Merck Pharmaceutical Company, Experimental Station, Wilmington, Delaware 19880-0402, USA.

出版信息

J Med Chem. 1995 Jul 21;38(15):2938-45. doi: 10.1021/jm00015a016.

DOI:10.1021/jm00015a016

PMID:7636854

Abstract

The identification of the AT1 and AT2 receptor subtypes has stimulated interest in developing balanced angiotensin II receptor antagonists. A series of 5-(3-amidopropanoyl)imidazoles has been prepared which possess balanced affinity for the AT1 and AT2 receptors. XR510 (1), 1-[[2'-[[(isopentoxycarbonyl)amino]sulfonyl]-3- fluoro(1,1'-biphenyl)-4-yl]methyl]-5-[3-(N-pyridin-3- ylbutanamido)propanoyl]-4-ethyl-2-propyl-1H-imidazole, potassium salt, exhibits subnanomolar affinity for both receptor sites. XR510 is very active in lowering blood pressure in renal hypertensive rats and furosemide-treated dogs following oral administration.

摘要

AT1和AT2受体亚型的鉴定激发了人们对开发平衡型血管紧张素II受体拮抗剂的兴趣。已制备出一系列对AT1和AT2受体具有平衡亲和力的5-(3-氨基丙酰基)咪唑。XR510（1），即1-[[2'-[[(异戊氧基羰基)氨基]磺酰基]-3-氟(1,1'-联苯)-4-基]甲基]-5-[3-(N-吡啶-3-基丁酰胺基)丙酰基]-4-乙基-2-丙基-1H-咪唑钾盐，对两个受体位点均表现出亚纳摩尔亲和力。口服给药后，XR510在降低肾性高血压大鼠和速尿治疗犬的血压方面非常有效。