Imidazo-thiazine, -diazinone and -diazepinone derivatives. Synthesis, structure and benzodiazepine receptor binding.
In our search for new compounds acting on benzodiazepine receptors among the fused 2-thiohydantoin derivatives, a series of arylidene imidazo[2,1-b]thiazines was synthesized. The 1,2- and 2,3- cyclized derivatives of mono- and di-substituted Z-5-arylidene-2-thiohydantoins were examined (the X-ray crystal structure of Z-2-cinnamylidene-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3(2H)-one was determined) and compared with the diphenyl derivatives. To investigate the influence of the type of annelated ring on the biological activity, imidazo[2,1-b]pyrimidinone and imidazo[2,1-b]diazepinone derivatives were obtained. The method used in annelation (1,2- and 2,3-cyclized isomers with the exception of fused arylidene imidazothiazines), the substitution pattern (arylidene towards diphenyl) as well as the character of the annelated ring had minor influence on the benzodiazepine receptor affinity of 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.
Kieć-Kononowicz
K
K
Department of Chemical Technology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, PL-30-688 Kraków, Poland. mfkonono@kinga.cyf-kr.edu.pl
Karolak-Wojciechowska
J
J
Müller
C E
CE
Schumacher
B
B
Pekala
E
E
Szymańska
E
E
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D003975:Diazepam / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D058787:GABA-A Receptor Antagonists; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014961:X-Ray Diffraction
D058787:GABA-A Receptor Antagonists; D011744:Pyrimidinones; D011963:Receptors, GABA-A; D013843:Thiazines; D003975:Diazepam