European Journal of Medicinal Chemistry 2012-12-01

Synthesis and biological evaluation of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amines and their pyrido and pyrazino analogues as Ser/Thr kinase inhibitors.

Yvonnick Loidreau, Pascal Marchand, Carole Dubouilh-Benard, Marie-Renée Nourrisson, Muriel Duflos, Olivier Lozach, Nadège Loaëc, Laurent Meijer, Thierry Besson

Index: Eur. J. Med. Chem. 58 , 171-83, (2012)

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Abstract

A useful and rapid access to libraries of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amines and their pyrido and pyrazino analogues was designed and optimized for the first time via microwave-accelerated condensation and Dimroth rearrangement of the starting anilines with N'-(2-cyanoaryl)-N,N-dimethylformimidamides obtained by reaction of thiophene precursors with dimethylformamide dimethylacetal. The inhibitory potency of the final products against five protein kinases (CDK5/p25, CK1δ/ɛ, GSK3α/β, DYRK1A and CLK1) was estimated. N-arylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4-amine series of compounds (4a-j) turned out to be particularly promising for the development of new pharmacological inhibitors of CK1 and CLK1 kinases.Copyright © 2012 Elsevier Masson SAS. All rights reserved.