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

Abstract 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)-1 H -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.