Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
Bioorg Med Chem Lett. 2012 Jan 1;22(1):410-4. doi: 10.1016/j.bmcl.2011.10.124. Epub 2011 Nov 7.
A number of 2-substituted tetrahydroindazolones were synthesized by three-component condensation reaction of 1,3-diketones, substituted hydrazines, benzaldehydes, and Yb(OTf)(3) as a catalyst in [bmim][BF(4)] ionic liquid using a simple, efficient, and economical one-pot method. The synthesized tetrahydroindazolones were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. 3,4-Dichlorophenyl tetrahydroindazolone derivative (15) inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 62% and 58%, respectively. 2,3-Diphenylsubstituted tetrahydroindazolone derivatives, inhibited the cell proliferation of HT-29 cells by 65-72% at a concentration of 50 μM. In general, the tetrahydroindazolones showed modest inhibition of c-Src kinase where 4-tertbutylphenyl- and 3,4-dichlorophenyl- derivatives showed the inhibition of c-Src kinase with IC(50) values of 35.1 and 50.7 μM, respectively.
合成了一系列 2-取代的四氢吲唑酮，方法是在 [bmim][BF4]离子液体中，用 1,3-二酮、取代肼、苯甲醛和 Yb(OTf)3 作为催化剂，通过简单、高效、经济的一锅法进行三组分缩合反应。对合成的四氢吲唑酮进行了人结肠癌细胞（HT-29）、人卵巢腺癌（SK-OV-3）的细胞增殖抑制和 c-Src 激酶活性评价。3,4-二氯苯基四氢吲唑酮衍生物（15）对 HT-29 和 SK-OV-3 细胞的增殖抑制率分别为 62%和 58%。2,3-二苯基取代的四氢吲唑酮衍生物在 50 μM 浓度下对 HT-29 细胞的增殖抑制率为 65-72%。一般来说，四氢吲唑酮对 c-Src 激酶有适度的抑制作用，其中 4-叔丁基苯基和 3,4-二氯苯基衍生物对 c-Src 激酶的抑制作用的 IC50 值分别为 35.1 和 50.7 μM。
