(E)-1-(2-硝基乙烯基)和1-[N-(叔丁基甲酰基)]-取代1,4-二氢吡啶和2-吡啶酮的合成及其细胞毒活性

Drug design and delivery Pub Date : 1990-03-01
C Im, E E Knaus, R P Thuynsma, T M Allen
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引用次数: 0

摘要

合成了核取代的1,4-二氢吡啶(7a-c)的1-(2-硝基)衍生物,以及1,4-二氢吡啶(9a-c)或2-吡酮(11a-c)的1-(n -叔丁基-甲酰基)衍生物作为细胞毒性药物进行评估(结构见表1)。L1210法测定的体外细胞毒活性表明,1,4-二氢吡啶环上的4-取代基是1-(2-硝基)(7)和1-(n-叔丁基甲酰基)(9)系列活性的决定因素,相对活性顺序为n-Bu > Ph > Me。在1-(n -叔丁基甲酰基)系列中,1,4-二氢吡啶衍生物(9)通常比2-吡啶酮衍生物(11)具有更大的细胞毒性。活性最高的化合物是1-(n-叔丁基甲酰基)-3-(4,4-二甲基氯唑啉-2-基)-4-n -丁基-1,4-二氢吡啶(9b),但其活性比参比标准品美伐兰低2-3 log单位。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and cytotoxic activity of (E)-1-(2-nitrovinyl) and 1-[N-(tert-butylformiminyl)]-substituted 1,4-dihydropyridines and 2-pyridones.

1-(2-Nitrovinyl) derivatives of nuclear substituted 1,4-dihydropyridines (7a-c), and 1-(N-tert-butyl-formiminyl) derivatives of 1,4-dihydropyridines (9a-c) or 2-pyridones (11a-c) were synthesized for evaluation as cytotoxic agents (see Table I for structures). The in vitro cytotoxic activities, determined in the L1210 assay, indicated that the 4-substituent on a 1,4-dihydropyridine ring system was a determinant of activity in both the 1-(2-nitrovinyl) (7) and 1-(N-tert-butylformiminyl) (9) series, the relative activity order being n-Bu > Ph > Me. In the 1-(N-tert-butylformiminyl) series, the 1,4-dihydropyridine derivatives (9) were generally more cytotoxic than the 2-pyridone derivatives (11). The most active compound was 1-(N-tert-butylformiminyl)-3-(4,4-dimethyloxazolin-2-yl)-4-n -butyl-1,4- dihydropyridine (9b), but it was 2-3 log units less active than the reference standard melphalan.

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