Chemical and Pharmaceutical Bulletin p. 1510 - 1520 (1996)
Update date:2022-08-02
Topics:
Sakurai, Shunichiro
Ogawa, Nobuo
Suzuki, Tomio
Kato, Ken-Ichi
Ohashi, Tetsuo
Yasuda, Shingo
Kato, Hideo
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 μM) and TXA2 synthase inhibitory activity (IC50=0.39 μM).
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