Nguyen C H, Bisagni E, Lavelle F, Bissery M C, Huel C
URA 1387 CNRS, Synthèse Organique, Institut Curie, Orsay, France.
Anticancer Drug Des. 1992 Jun;7(3):219-33.
A new class of antineoplastic agents, 4-methyl-pyrido[4,3-b]indoles (5) and the related 4-hydroxymethyl derivatives (7), has been synthesized by a new pathway. Key transformations include regiospecific chlorination at the C(4)-position of 3-nitro-4-hydroxy-5-methyl-pyridin-2-(1H)-one (11) and photochemical cyclization of the intermediate triazolopyridones (15). This new synthesis was developed since an attempt to prepare 4-hydrazino-5-ethoxymethyl-pyridin-2-(1H)-one (10b) by the method previously used to obtain 4-hydrazino-5-methyl-pyridin-2-(1H)-one (10a) failed. The biological results obtained in different in vitro and in vivo models indicate that the substitution of the 4-CH3 by a 4-CH2OH group leads to a decrease of the antitumor properties.
一类新型抗肿瘤药物，4-甲基吡啶并[4,3 - b]吲哚（5）及相关的4-羟甲基衍生物（7），已通过一条新途径合成。关键转化步骤包括在3-硝基-4-羟基-5-甲基吡啶-2-(1H)-酮（11）的C(4)位进行区域选择性氯化以及中间体三唑并吡啶酮（15）的光化学环化。开发这种新合成方法是因为之前用于制备4-肼基-5-甲基吡啶-2-(1H)-酮（10a）的方法尝试制备4-肼基-5-乙氧基甲基吡啶-2-(1H)-酮（10b）失败了。在不同体外和体内模型中获得的生物学结果表明，将4-CH3替换为4-CH2OH基团会导致抗肿瘤性能下降。
