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首页> 外文期刊>Zeitschrift fur Naturforschung, B. A Journal of Chemical Sciences >Synthesis of structural analogues of GGT1-DU40, a potent GGTase-1 inhibitor
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Synthesis of structural analogues of GGT1-DU40, a potent GGTase-1 inhibitor

机译：强大的GGTase-1抑制剂GGT1-DU40的结构类似物的合成

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摘要

A series of new substituted pyrazoles 2-12 have been synthesized. The synthesized compounds are structural analogues of GGT1-DU40 1, a highly potent and selective inhibitor of protein geranylgeranyltransferase I (GGTase-I) both in vitro and in vivo. The implications of GGTase-I in oncogenesis have highlighted its potential as a cancer therapeutic target. Accordingly, the development of GGTase-I inhibitors has been a subject of much interest. The synthesis of 2-12 stemmed from the acetylation or acylation of N-function of amino acids to produce suitably modified amino acids. Meanwhile, the substituted pyrazole subunit originated from the reaction of ethyl nicotinate with gamma-butyrolactone followed by condensation of the resultant beta-keto lactone with (3,4-dichlorophenyl) hydrazine. The operations of O-alkylation and thioetherification on the resultant intermediate eventually produced the substituted pyrazole fragment. The amidation of the latter with amino acid derivatives finally rendered 2-12 in good to excellent yields.
机译：已经合成了一系列新的取代的吡唑2-12。合成的化合物是GGT1-DU40 1的结构类似物，GGT1-DU40 1是一种在体外和体内均有效且选择性强的蛋白geranylgeranyltransferase I（GGTase-I）抑制剂。 GGTase-I在肿瘤发生中的意义突出了其作为癌症治疗靶标的潜力。因此，GGTase-I抑制剂的开发已经引起人们极大的兴趣。 2-12的合成源于氨基酸N功能的乙酰化或酰化，以产生适当修饰的氨基酸。同时，取代的吡唑亚基源自烟酸乙酯与γ-丁内酯的反应，然后将所得的β-酮内酯与（3，4-二氯苯基）肼缩合。在所得中间体上进行O-烷基化和硫醚化的操作最终产生了取代的吡唑片段。后者与氨基酸衍生物的酰胺化最终以良好至优异的产率得到2-12。

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