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A useful and rapid access to libraries of N-arylbenzo[ b]furo[3,2- d]pyrimidin-4-amines ( 1) and their novel benzo[ b]thieno[3,2- d]pyrimidin-4-amine analogues ( 2) was investigated for the first time. Title compounds were obtained via microwave-accelerated condensation and of suitable anilines with N′-(2-cyanaryl)- N, N-dimethylformimidamides obtained by reaction of benzo[ b]furane and benzo[ b]thiophene precursors with N, N-dimethylformamide dimethyl acetal. This work also demonstrates that well-controlled parameters offer comfortable use of and are both safe and beneficial to the environment. Some products obtained in this article exhibit interesting in vitro antiproliferative effects. [ABSTRACT FROM AUTHOR]

The study is performed under microwave irradiation. [ABSTRACT FROM AUTHOR]

Efficient microwave-assisted chemical processes were applied to the synthesis of an array of novel N -(4-methoxyphenylamino)-2-methyl benzo-, pyrido- or pyrazino-thieno[3,2- d ]pyrimidin-4-amine derivatives. These heteroaromatic systems were envisioned as potent bioisosteric analogues of MPC-6827 , an anticancer agent previously developed until phase II clinical studies. A brief evaluation and comparison of their antiproliferative activity on HT-29 and Caco-2, two human colorectal cancer cell lines, were also reported. At the tested concentrations (5 and 10 µM), thieno[3,2- d ]pyrimidin-4-amines 4a and 4c exhibited an inhibitory effect similar to MPC-6827 on human colorectal cancer cell proliferation.

We previously highlighted the interest in 6,5,6-fused tricyclic analogues of 4-aminoquinazolines as kinase inhibitors in the micromolar to the nanomolar range of IC 50 values. For the generation of chemical libraries, the formamide-mediated cyclization of the cyanoamidine precursors was carried out under microwave irradiation in an eco-friendly approach. In order to explore more in-depth the pharmacological interest in such tricyclic skeletons, the central five member ring, i.e., thiophène or furan, was replaced by a pyrrole to afford 9H-pyrimido[5,4-b]- and [4,5-b]indol-4-amine derivatives inspired from harmine. The inhibitory potency of the final products was determined against four protein kinases (CDK5/p25, CK1/ε, GSK3 and DYRK1A). As a result, we have identified promising compounds targeting CK1/ε and DYRK1A and displaying micromolar and submicromolar IC 50 values., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.