Ravi Kumar N, Poornachandra Y, Krishna Swaroop D, Jitender Dev G, Ganesh Kumar C, Narsaiah B
Fluoroorganic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
Bioorg Med Chem Lett. 2016 Nov 1;26(21):5203-5206. doi: 10.1016/j.bmcl.2016.09.062. Epub 2016 Sep 28.
A series of novel pyrido[2',3':3,4] pyrazolo[1,5-a]pyrimidine derivatives 6-9 were prepared in single step starting from 3-amino-6-(trifluoromethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate 5 on reaction with symmetrical and unsymmetrical aliphatic and aromatic 1,3-diketones/α,β unsaturated ketones/α,β unsaturated keto ethers under conventional method. All the final compounds 6a-c, 8a-b and 9a-l were screened for anticancer activity against five human cancer cell lines such as PC-3 (CRL-1435), MDA-MB-231 (HTB-26), Hep G2 (HB-8065), HeLa (CCL-2) and normal HUVEC (CRL-1730). Compounds 8a, 9f and 9k which showed promising anticancer activity have been identified. Further, the promising compounds (8a and 9f) were able to inhibit the human topoisomerase I (TopI) activity similar to that of camptothecin.
从3-氨基-6-(三氟甲基)-1H-吡唑并[3,4-b]吡啶-5-羧酸酯5出发，通过常规方法与对称和不对称脂肪族及芳香族1,3-二酮/α,β-不饱和酮/α,β-不饱和酮醚反应，一步制备了一系列新型吡啶并[2',3':3,4]吡唑并[1,5-a]嘧啶衍生物6-9。对所有最终化合物6a-c、8a-b和9a-l针对五种人类癌细胞系进行了抗癌活性筛选，这五种细胞系分别为PC-3(CRL-1435)、MDA-MB-231(HTB-26)、Hep G2(HB-8065)、HeLa(CCL-2)以及正常的人脐静脉内皮细胞(HUVEC，CRL-1730)。已鉴定出显示出有前景抗癌活性的化合物8a、9f和9k。此外，有前景的化合物(8a和9f)能够抑制人拓扑异构酶I(TopI)的活性，其效果与喜树碱类似。
