首页> 外国专利> DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF 1-METHYL-1, 4-DIHYRDOINDENO1,2-CPYRAZOLE ANALOGUES AS POTENTIAL ANTICANER AGENTS TARGETING TUBULIN COLCHICINE BINDING SITE

DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF 1-METHYL-1, 4-DIHYRDOINDENO1,2-CPYRAZOLE ANALOGUES AS POTENTIAL ANTICANER AGENTS TARGETING TUBULIN COLCHICINE BINDING SITE

机译:1-甲基-1,4-二氢吲哚并[1,2-C]吡唑类似物作为潜在的抗癌剂靶向微管蛋白酪氨酸结合位点的设计,合成及生物学评价

摘要

The invention discloses an indenopyrazole small-molecule tubulin inhibitor, which is characterized by having a structure represented by general formula I:; embedded image ;wherein R represents NH2 or NHOH; the invention also discloses a preparation method of the indenopyrazole compound, or pharmaceutical salts thereof. The compound of the present invention is an indenopyrazole small-molecule tubulin inhibitor having a novel structure, and has very strong proliferation inhibition activity to human hepatocellular carcinoma (HepG2) cells, human prostate carcinoma (PC3) cells, human cervical carcinoma (HeLa) cells, human breast adenocarcinoma (MCF-7) cells, and human leukemia (K562) cells; the compound is similar to colchicine in mechanism of action, and thus capable of inhibiting tubulin polymerization; the compound is significant for enhancing the specificity and effectiveness of drugs, reducing toxic and side effects, preventing drug tolerance, and so on.
机译:本发明公开了一种茚并吡唑小分子微管蛋白抑制剂,其特征在于具有通式I所示的结构: “嵌入式图像” ;其中R代表NH 2 或NHOH;本发明还公开了茚并吡唑化合物或其药用盐的制备方法。本发明的化合物是具有新颖结构的茚并吡唑小分子微管蛋白抑制剂,并且对人肝细胞癌(HepG2)细胞,人前列腺癌(PC3)细胞,人宫颈癌(HeLa)细胞具有非常强的增殖抑制活性。 ,人乳腺腺癌细胞(MCF-7)和人白血病(K562)细胞;该化合物在作用机理上类似于秋水仙碱,因此能够抑制微管蛋白聚合。该化合物对于增强药物的特异性和有效性,减少毒性和副作用,防止药物耐受性等具有重要意义。

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