Yonan P K, Novotney R L, Woo C M, Prodan K A, Hershenson F M
J Med Chem. 1980 Oct;23(10):1102-8. doi: 10.1021/jm00184a008.
The synthesis and biological evaluation of a series of alpha, alpha-bis[(dialkylamino)alkyl]phenylacetamides, 2, are presented. These compounds are structurally related to the antiarrhythmic agent disopyramide (1) and in many cases were found to possess greater antiarrhythmic activity in coronary ligated dogs. Within this series of compounds, a separation of the antiarrhythmic properties from the unwanted cardiac depressant side effects observed with the parent compound, 7, was also often attained. A discussion of the structure-activity relationships within the series is presented; this work has culminated in the identidiction of compound 35 (disobutamide) as a candidate for clinical evaluation as an antiarrhythmic agent in man.
本文介绍了一系列α,α-双[（二烷基氨基）烷基]苯乙酰胺（2）的合成及生物学评价。这些化合物在结构上与抗心律失常药物双异丙吡胺（1）相关，并且在许多情况下，发现它们在冠状动脉结扎犬中具有更强的抗心律失常活性。在这一系列化合物中，还常常能够将抗心律失常特性与母体化合物7所观察到的不良心脏抑制副作用区分开来。本文对该系列化合物的构效关系进行了讨论；这项工作最终确定化合物35（二异丁酰胺）作为一种抗心律失常药物用于人体临床评价的候选药物。
