Design and synthesis of new [1,2,3]triazolo[4,5-d]pyrimidine derivatives as potential antiproliferative agents

Abstract

A new series possessing [1,2,3]triazolo[4,5-d]pyrimidine scaffold was synthesized and biologically evaluated for potential antiproliferative activity. Fourteen compounds were selected for in vitro anticancer assay over a panel of 60 cell lines at National Cancer Institute (NCI), USA. The most sensitive cell lines to the synthesized compounds were leukemia (K-562 and SR), nonsmall cell lung cancer HOP-92, and melanoma MDA-MB- 435. Compounds 12 and 24 exerted broad spectrum activity against most cell panel, while compounds 14, 21, and 23 exhibited effectiveness toward specific cell lines belong to different tumor subpanels. Accordingly, SAR, COMPARE analyses, and in silico ADME profiling were discussed for the target compounds. In addition, compounds 11 and 22 exerted good FGFR3 inhibitory activity with 58.8 and 46.7% at 100 μM, respectively. Taken as a whole, the present study revealed that the new series can be considered as promising lead for further development of more potent anticancer agents as well as FGFR3 kinase potential inhibitors. © 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.