Life Sciences Research Division, Korea Institute of Science and Technology, 39-1 Hawolgok-Dong, Seongbuk-Gu, Seoul 136-791, South Korea.
Bioorg Med Chem Lett. 2010 Mar 1;20(5):1630-3. doi: 10.1016/j.bmcl.2010.01.029. Epub 2010 Jan 20.
A novel series of 3,5,6-trisubstituted pyrazolo[4,3-d]pyrimidin-7-one derivatives, especially 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-ones were synthesized and evaluated for their in vitro anticancer activities against various human cancer cell lines. The inhibitory activities for several kinases have also been tested. The prepared compounds library exhibited significant anticancer activity towards HT-29 colon and DU-145 prostate cancer cell lines. The structure-activity relationships of the 6-N-arylcarboxamidopyrazolo[4,3-d]pyrimidin-7-one scaffold at R(1), R(2) and R(3) have been elucidated. Among the synthesized compounds, 12b was the most active compound with GI(50) value of 0.44microM and 1.07microM against HT-29 and DU-145 cell lines, respectively, and 13a was the most selective compound towards colon cancer cell line.
一系列新型 3,5,6-三取代吡唑并[4,3-d]嘧啶-7-酮衍生物，特别是 6-N-芳基羧酰胺吡唑并[4,3-d]嘧啶-7-酮，被合成并评估了它们对各种人类癌细胞系的体外抗癌活性。还测试了几种激酶的抑制活性。所制备的化合物库对 HT-29 结肠和 DU-145 前列腺癌细胞系表现出显著的抗癌活性。已经阐明了 6-N-芳基羧酰胺吡唑并[4,3-d]嘧啶-7-酮支架在 R(1)、R(2)和 R(3)处的构效关系。在所合成的化合物中，12b 是最具活性的化合物，对 HT-29 和 DU-145 细胞系的 GI(50)值分别为 0.44μM 和 1.07μM，13a 对结肠癌细胞系具有最高的选择性。
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