Design, microwave assisted synthesis and pharmacological activities of substituted pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate derivatives

Abstract

Background and aimThe current need for the discovery and development of new lead compounds exhibiting optimal antitumor potency as well as anti-inflammatory activity. Due to biological activity of significant number of compounds containing condensed pyrimidine ring system and our interest in MCRs reactions, we wish to report the synthesis of 4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate. MethodA novel one pot multi-component reaction of substituted benzaldehyde, ethyl cyanoacetate, 2-amino benzothiazole to give pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate was described. The operational simplicity, environmental friendly conditions, regioselective formation of target product and high yield in significantly very short reaction time were major benefits. Result and discussionStructural assignments based on spectroscopic data (FT-IR, 1H NMR, mass spectra). Compounds evaluated for in vitro on panel of 60 different human tumor cell lines derived from nine neoplastic cancer types at NCI, and for the in vitro anti-inflammatory activity. Compound ethyl(4R)-2-amino-6,9-dimethyl-4-[4-(dimethylamino)phenyl]-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate (4i) was found to possess good antiproliferative activity and compound ethyl(4R)-2-amino-6-chloro-4-(3,4,5-trimethoxyphenyl)-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate (4g) was found to posses potent anti-inflammatory activity and compounds 4a, 4b, 4h also found to be significant anti-inflammatory activity. ConclusionThe obtained results prove the necessity for further investigations to clarify the features underlying the antitumor potential of tested compounds and had potential to design lead for anti-inflammatory activity.