Novel Pyrano[2,3-d]thiazole and Thiazolo[4,5-b]pyridine Derivatives: One-pot Three-component Synthesis and Biological Evaluation as Anticancer Agents, c-Met, and Pim-1 Kinase Inhibitors

摘要

Preparation of pyrano[2,3-d]thiazole and thiazolo[4,5-b]pyridine derivatives through multicomponent reactions (MCRs) was achieved by the reaction of 2-(2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)thiazol-4(5H)-one with various active methylene reagents such as ethyl cyanoacetate or malononitrile in basic conditions containing diverse aromatic aldehyde. Furthermore, this study aims to evaluate the in vitro cytotoxic activity of the synthetic compounds against six cancer cell lines, and all the prepared compounds revealed valuable activity compared with the CHS-828, which is the 2-[6-(4-chlorophenoxy)hexyl]-1-cyano-3-pyridin-4-ylguanidine as the standard drug. Some of the pyrano[2,3-d]thiazole and thiazolo[4,5-b]pyridine derivatives showed the highest antitumor activity towards the six cancer cell lines. Moreover, (c-Met) enzymatic activity of the most potent compounds showed that compounds 3b 2-(2-amino-4,5,6,7 tetrahydrobenzo[b]thiophen-3-yl)-5-hydroxy-7-(2-hydroxy-phenyl)-7H-pyrano[2,3-d]thiazole-6 carbonitrile and 5e 2-(2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)-5-hydroxy-7-phenyl-4,7-dihydrothiazolo[4,5-b]pyridine-6-carbonitrile were with higher activities than foretinib. Three compounds were selected to examine their Pim-1 kinase where compounds 3b and 7b showed the highest inhibitions.