Atwell G J, Rewcastle G W, Baguley B C, Denny W A
J Med Chem. 1987 Apr;30(4):664-9. doi: 10.1021/jm00387a014.
The synthesis, physicochemical properties, and antitumor activity of a series of N-[2-(dialkylamino)alkyl]-acridine-4-carboxamides are reported. The compounds bind to DNA by intercalation, but exist under physiological conditions as monocations due to the weakly basic acridine chromophore (pKa = 3.5-4.5). The acridine-4-carboxamides show very broad structure-activity relationships (SAR) for antileukemic activity, with substituents at nearly all acridine positions proving acceptable. The compounds also show remarkable activity against the Lewis lung solid tumor in vivo, with several analogues capable of effecting 100% cures of the advanced disease. The broad SAR and high solid-tumor activity of the 9-acridine-4-carboxamides imply they should be considered as a completely new class of antitumor agent.
报道了一系列N-[2-(二烷基氨基)烷基]-吖啶-4-甲酰胺的合成、物理化学性质及抗肿瘤活性。这些化合物通过嵌入作用与DNA结合，但由于吖啶发色团碱性较弱（pKa = 3.5 - 4.5），在生理条件下以单阳离子形式存在。吖啶-4-甲酰胺在抗白血病活性方面表现出非常广泛的构效关系（SAR），几乎所有吖啶位置的取代基都被证明是可接受的。这些化合物在体内对Lewis肺癌实体瘤也显示出显著活性，有几种类似物能够使晚期疾病实现100%治愈。9-吖啶-4-甲酰胺广泛的SAR和高实体瘤活性表明它们应被视为一类全新的抗肿瘤药物。
