Synthesis of novel trifluoromethyl substituted furo[2,3-b]pyridine and pyrido[3 ',2 ':4,5]furo[3,2-d]pyrimidine derivatives as potential anticancer agents

摘要

A series of novel trifluoromethyl substituted furo[2,3-b]pyridine and pyrido[31,21:4,5]furo[3,2-d] pyrimidine derivatives 3a-b, 6a-k, 9, 10a-b, Ila-c and 12a-c were prepared from 2-carbethoxy-3-amino-6-trifluoromethyl furo[2,3-blpyridine 1 under different set of conditions. Compounds functionalized with oxadiazole 11a-c were also prepared from 2-carbohydrazide-3-amino-6-trifluoromethyl furo[2,3-b] pyridine 4. All the final products were screened for anticancer activity against four human cancer cell lines such as Neuro-2a, Hela, A549 and COLO 205 as well as normal human lung cell line, IMR-90. All the compounds showed promising anticancer activity against all the tested cell lines at <25 mu M concentration except 5b, 6d, 6e and 6k. The selectivity index (SI) values have also been calculated for all the tested compounds in comparison to the normal cell line. Compounds 6g, 10a, 10b, and na were considered as potential leads which showed cytotoxicity with IC50 values of 10, 10.7, 11.0 and 10.5 mu M, respectively. Compounds 7 and 12a were considered as highly potent exhibiting promising cytotoxicity with IC50 value of 5.8 and 3.6 mu M, respectively. (C) 2015 Elsevier Masson SAS. All rights reserved.