Agrawal K C, Sartorelli A C
J Med Chem. 1978 Feb;21(2):218-21. doi: 10.1021/jm00200a015.
The effects of various structural modifications on the antineoplastic activity of the benzenesulfonylhydrazone of 2-formylpyridine N-oxide have been ascertained in mice bearing either Sarcoma 180 or leukemia L1210. To accomplish this a variety of derivatives substituted at the aldehyde proton, the aryl ring, and the 4 position of the pyridine nucleus were synthesized. Antineoplastic activity was retained when nitro, amino, chloro, bromo, fluoro, and methoxy groups were introduced into either the meta or para positions of the phenyl ring of the parent compound. In addition, substitution of the terminal phenyl group by a pyridine ring or by a bulky aromatic ring such as alpha-naphthyl, beta-naphthyl, or fluorenyl did not abolish the marked antitumor activity expressed by this class of agents. Insertion of a nitro function or a morpholino group in the 4 position of the pyridine nucleus of the benzenesulfonylhydrazone of 2-formylpyridine N-oxide resulted in two potent anticancer agents, while the introduction of a chloro function in the 4 position led to a pronounced decrease in biological activity. Furthermore, the essentiality of the aldehydic proton for tumor-inhibitor activity was demonstrated by the inactivity of two derivatives in which the aldehydic proton was replaced by a methyl group or by an oxygen atom.
在患有肉瘤180或白血病L1210的小鼠中，已确定了各种结构修饰对2-甲酰基吡啶N-氧化物苯磺酰腙抗肿瘤活性的影响。为此，合成了在醛质子、芳环和吡啶核的4位上被取代的各种衍生物。当在母体化合物苯环的间位或对位引入硝基、氨基、氯、溴、氟和甲氧基时，抗肿瘤活性得以保留。此外，用吡啶环或大体积芳环（如α-萘基、β-萘基或芴基）取代末端苯基，并没有消除这类药物所表现出的显著抗肿瘤活性。在2-甲酰基吡啶N-氧化物苯磺酰腙的吡啶核4位插入硝基或吗啉基团，产生了两种有效的抗癌药物，而在4位引入氯官能团导致生物活性显著降低。此外，两种醛质子被甲基或氧原子取代的衍生物无活性，证明了醛质子对肿瘤抑制活性的重要性。
