Imidazo-thiazine, -diazinone and -diazepinone derivatives. Synthesis, structure and benzodiazepine receptor binding

In our search for new compounds acting on benzodiazepine receptors among th e fused 2-thiohydantoin derivatives, a series of arylidene imidazo[2,1-b]th iazines was synthesized. The 1,2- and 2,3- cyclized derivatives of mono- an d di-substituted Z-5-arylidene-2-thiohydantoins were examined (the X-ray cr ystal structure of Z-2-cinnamylidene-6,7-dihydro-5H-imidazo[2,1-b][1,3]thia zin-3(2H)-one was determined) and compared with the diphenyl derivatives. T o investigate the influence of the type of annelated ring on the biological activity, imidazo[2,1-b]pyrimidinone and imidazo[2,1-b]diazepinone derivat ives were obtained. The method used in annelation (1,2- and 2,3-cyclized is omers with the exception of fused arylidene imidazothiazines), the substitu tion pattern (arylidene towards diphenyl) as well as the character of the a nnelated ring had minor influence on the benzodiazepine receptor affinity o f the investigated compounds. It appears that the greatest influence on the biological activity has the character and position of the substituents on the arylidene ring. (C) 2001 Editions scientifiques et medicales Elsevier S AS.