Thieno3,2-ediazepinediones and 3-Thienylimidazolidinediones Syntheses: Regio-Controlled Ring Opening of Thiaisatoic Anhydride by α-Amino Acids.

摘要

In previous biological studies we demonstrated that two specific p38 mitogen-activated protein (MAP) kinase inhibitors, derived from imidazole (SB202190 and SB203580), were also able to directly and selectively interact with a G-protein-coupled receptor, the cholecystokinin receptor subtype CCK1. In the same way, it was also shown that two CCK benzodiazepines antagonists (L3 64,718 and L365,260) were able to regulate p38 MAP kinase activity [1]. These cross-interactions between these MAP kinase inhibitors and these CCK receptor antagonists with the CCK1 receptor and the p38 MAP kinase suggested that new kinase inhibitors could be designed on the model of CCK receptor antagonists. The chemistry of diazepines being exhaustively described in the literature with the benzene series, we have focused our chemical work on the bioisosteric thieno[l,4] diazepine moiety, that has already proven its effectiveness in medicinal chemistry to design drugs such as Clotiazepam. Our first chemical goal was to develop an efficient methodology to access this scaffold from the regio-controlled ring opening of thiaisatoic anhydride.