Sakurai S, Ogawa N, Suzuki T, Kato K, Ohashi T, Yasuda S, Kato H
Research and Development Division, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
Chem Pharm Bull (Tokyo). 1996 Aug;44(8):1510-20. doi: 10.1248/cpb.44.1510.
As part of our search for a dual inhibitor possessing both thromboxane A2 (TXA2) receptor antagonistic and TXA2 synthase inhibitory activities, some [[(benzenesulfonamido)alkyl]phenyl]alkanoic acid derivatives possessing a pyridyl or imidazolyl group were synthesized. Their TXA2 receptor antagonistic and TXA2 synthase inhibitory activities were evaluated in terms of the inhibitory effects on U-46619-induced guinea-pig platelet aggregation and on thromboxane B2 (TXB2) production in human platelets, respectively. It was found that 3-[4-[2-(1-imidazolyl)-1-(4-chlorobenzenesulfonamido)ethyl]phenyl] propionic acid (22a), containing an imidazolyl group, is a well-balanced dual inhibitor having both TXA2 receptor antagonistic activity (IC50 = 0.31 microM) and TXA2 synthase inhibitory activity (IC50 = 0.39 microM).
作为我们寻找兼具血栓素A2（TXA2）受体拮抗活性和TXA2合酶抑制活性的双重抑制剂工作的一部分，合成了一些带有吡啶基或咪唑基的[[(苯磺酰胺基)烷基]苯基]链烷酸衍生物。分别通过对U-46619诱导的豚鼠血小板聚集的抑制作用以及对人血小板中血栓素B2（TXB2）生成的抑制作用，来评估它们的TXA2受体拮抗活性和TXA2合酶抑制活性。结果发现，含有咪唑基的3-[4-[2-(1-咪唑基)-1-(4-氯苯磺酰胺基)乙基]苯基]丙酸（22a）是一种兼具TXA2受体拮抗活性（IC50 = 0.31 microM）和TXA2合酶抑制活性（IC50 = 0.39 microM）的平衡良好的双重抑制剂。
