内皮素受体拮抗剂CPU0213的生物活性及抑制ETA及ETB受体的作用(英文)  

Endothelin Receptor Antagonist Activity and Selective Blocking the ET_A and ET_B of Compound 0213

作　　者：戴德哉[1] 吉民[1] 黄敏[2] 刘立钢[2] 

机构地区：[1]中国药科大学药理学研究室 [2]中国药科大学新药研究中心,南京210009

出　　处：《中国药科大学学报》2004年第6期552-557,共6页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.30230170,No.30171078)~~

摘　　要：目的从合成的77个新化合物中经过生物活性筛选后得到新内皮素受体拮抗剂CPU0213。方法采用功能性抑制大鼠去内皮胸主动脉收缩及心肌ETA、ETB亚型放射受体结合实验。结果CPU0213抑制ETA及ETB受体作用最强,ETA及ETB的pA2分别为(8.52±0.26)及(7.28±0.04),放射受体分析的IC50,ETA及ETB分别为(2.57±1.41)及(95±34)nmol/L。结论CPU0213的对受体的作用强度及选择性优于Bosentan(与文献比较)。AIM:To search for a novel endothelin receptor antagonist compound 0213 by testing its biological activities.METHOD: The functional suppression tests of endothelin-1 (ET-1) induced contraction of rat thoracic aorta and ET-1 binding on myocardium served as the preliminary tests for 77 new compounds and compound 0213 was chosen to search for the potency and selectivity of effects on the ET_~A and ET_~B receptor of rat myocardium,thoracic aortic and guinea pig bronchial smooth muscle.RESULT: Compound 0213 was effective to suppress the vaso-contraction and ET-1 bindings on rat myocardial membrane preparation.The pA_~2 to suppress ET-1 induced contraction of rat thoracic aorta (mediated by ET_~A ) and sarafotoxin (S6c) induced contraction of guinea pig bronchial smooth muscles (ET_~B mediated ) was (8.52±0.26) and (7.28±0.04),respectively. The potency to suppress ET_~A and ET_~B of compound 0213 was (2.57±1.41) nmol/L (n=9) and (95±34) nmol/L (n=5).The potency and selectivity of compound 0213 was better than that of Bosentan.CONCLUSION:A novel endothelin receptor antagonist compound 0213 is promising to be a useful agent in dealing with cardiovascular disorders.

关 键 词：内皮素受体拮抗剂 放射受体分析 心肌 血管平滑肌 

分 类 号：R96[医药卫生—药理学]