Synthesis of novel ethyl 2,4-disubstituted 8-(trifluoromethyl)pyrido [2',3':3,4]pyrazolo[1,5-a]pyrimidine-9-carboxylate derivatives as promising anticancer agents

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/alpha,beta unsaturated ketones/alpha,beta unsaturated keto ethers under conventional method. All the final compounds 6a-c, 8a-b and 9a-I were screened for anticancer activity against five human cancer cell lines such as PC-3 (CRL-1435), MDA-MB231 (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 (Topl) activity similar to that of camptothecin. (C) 2016 Elsevier Ltd. All rights reserved.