内皮素受体拮抗剂CPU 0213的生物活性及抑制ETA及ETB受体的作用

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CPU 0213.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:CPU 0213的对受体的作用强度及选择性优于Bosentan(与文献比较).

Endothelin Receptor Antagonist Activity and Selective Blocking the ETA and ETB of Compound 0213

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 ETA and ETB 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 pA2 to suppress ET-1 induced contraction of rat thoracic aorta (mediated by ETA) and sarafotoxin (S6c) induced contraction of guinea pig bronchial smooth muscles (ETB mediated ) was (8.52±0.26) and (7.28±0.04),respectively. The potency to suppress ETA and ETB 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.