We are aiming in this work to synthesize target molecules not only possess antitumor activities but also kinase inhibitors. The target molecules were obtained from dimedone, which reacted with triethoxymethane to produce a product that is capable for many heterocyclization reactions to give fused pyrazole, thiophene and isoxazole derivatives. Compounds 7b, 7c, 7d, 9b, 11, 12c, 12d, 14b, 16b, 17c, 17d, 18c, 18d, and 18e were the most cytotoxic compounds, their further tests toward the five tyrosine kinases c-Kit, Flt-3, VEGFR-2, EGFR, and PDGFR and Pim-1 kinase showed that compounds 7b, 7d, 11, 12c, 14b, 16b, 17d, 18d, and 18e were the most potent of the tested compounds toward the five tyrosine kinases and compounds 7b, 7d, 14b, 16b, and 18e were of the highest inhibitions toward Pim-1 kinase. PAINS the most cytotoxic compounds showed zero PAINS alert, therefore, these compounds can be used as useful drugs in the future.

中文翻译：

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使用二甲酮合成具有抗增殖，酪氨酸激酶和Pim-1激酶抑制作用的吡唑，异恶唑和噻吩衍生物

我们的目标是合成不仅具有抗肿瘤活性而且具有激酶抑制剂的靶分子。从二甲酮获得目标分子，该二甲酮与三乙氧基甲烷反应生成一种产物，该产物能够进行许多杂环反应以生成稠合的吡唑，噻吩和异恶唑衍生物。化合物7B，图7C，图7D，图9b，11，12C，12D，14B，16B，17C，17D，18C，18D，和18E是最细胞毒性化合物，它们朝向五个酪氨酸激酶的c-Kit，Flt-3的，VEGFR-2，EGFR，和PDGFR和PIM-1激酶表明，化合物进一步测试7b的，图7d，11，12C，14B，16B，测试的化合物中17d，18d和18e对五个酪氨酸激酶和化合物7b，7d，14b，16b和18e最有效对Pim-1激酶的抑制作用最高。PAINS最具细胞毒性的化合物显示出零的PAINS警戒，因此，这些化合物将来可以用作有用的药物。