Feller D R, Kamanna V S, Newman H A, Romstedt K J, Witiak D T, Bettoni G, Bryant S H, Conte-Camerino D, Loiodice F, Tortorella V
J Med Chem. 1987 Aug;30(8):1265-7. doi: 10.1021/jm00391a001.
Enantiostructure-activity studies of chlorophenoxybutyric and propionic acids have provided evidence for the dissociation of serum cholesterol lowering and platelet antiaggregatory activities from the adverse chloride ion channel mediated myotonic effects of these compounds. R-(+) propionic and butyric acid enantiomers, unlike achiral clofibric acid and the S-(-) isomers, did not inhibit chloride conductance in rat extensor digitorum longus muscle fibers in vitro but, like clofibric acid and the S-(-) isomers, retained the serum cholesterol lowering activity in a cholesterol-fed rat model. Additionally, a stereoselective and greater inhibition was observed for the R-(+) isomers against adenosine diphosphate and arachidonic acid induced human platelet aggregation.
氯苯氧基丁酸和丙酸的对映体结构-活性研究提供了证据，表明这些化合物的血清胆固醇降低和血小板抗聚集活性与由氯离子通道介导的不良强直性作用相分离。与非手性氯贝酸和S-(-)异构体不同，R-(+)丙酸和丁酸对映体在体外不抑制大鼠趾长伸肌纤维中的氯电导，但与氯贝酸和S-(-)异构体一样，在胆固醇喂养的大鼠模型中保留了血清胆固醇降低活性。此外，观察到R-(+)异构体对二磷酸腺苷和花生四烯酸诱导的人血小板聚集具有立体选择性且更强的抑制作用。
