Desai B N, Fowler K W, Chorvat R J, Frederick L G, Hatley F R, Rorig K J, Garthwaite S M
Cardiovascular Diseases Research Department, G.D. Searle and Company, Skokie, Illinois 60077.
J Med Chem. 1988 Nov;31(11):2158-64. doi: 10.1021/jm00119a017.
Analogues of the dibasic antiarrhythmic agent disobutamide (2) were prepared and evaluated for antiarrhythmic efficacy, myocardial depression, and anticholinergic activity. The replacement of an isopropyl group in disobutamide by an acetyl group led to the monobasic analogue SC-40230, 7a, which demonstrated good antiarrhythmic activity accompanied by less myocardial depressant and anticholinergic activities. In addition, it did not induce clear cytoplasmic vacuoles as did the parent compound. SC-40230 was chosen from among other analogues as a candidate for clinical evaluation. Other compounds prepared and evaluated included indolizidinones and a secondary amine isomer of disobutamide.
制备了二元抗心律失常药物二丁胺（2）的类似物，并对其抗心律失常疗效、心肌抑制作用和抗胆碱能活性进行了评估。用乙酰基取代二丁胺中的异丙基得到了一元类似物SC - 40230，即7a，它表现出良好的抗心律失常活性，同时心肌抑制和抗胆碱能活性较低。此外，它不像母体化合物那样诱导明显的细胞质空泡形成。从其他类似物中选择了SC - 40230作为临床评估的候选药物。制备并评估的其他化合物包括吲哚里西啶酮和二丁胺的仲胺异构体。
