Imidazo[2,1-b]thiazepines: synthesis, structure and evaluation of benzodiazepine receptor binding.
As a continuation of our search for new ligands acting on benzodiazepine receptors among the fused 2-thiohydantoin derivatives, a series of 5-substituted imidazo[2,1-b]thiazepines was synthesized and investigated in radioligand binding studies at the benzodiazepine binding site of GABA(A) receptors in rat brain cortical membranes. Among ortho-substituted 5-arylidene-imidazo[2,1-b]thiazepines compounds could be identified which exhibit affinity for the benzodiazepine binding site at low micromolar concentrations. X-ray structure analyses for two compounds (6ae and 6ag) have been performed. In order to analyze the structure-activity relationships, 3D models of all compounds have been completed (using X-ray data). Physicochemical properties calculated (log P and log D) as well as experimental thin layer chromatography data were examined.
Kieć-Kononowicz
Katarzyna
K
Department of Chemical Technology of Drugs, Jagiellonian University Medical College, ul Medyczna 9, PL 30-688 Kraków, Poland. mfkonono@cyf-kr.edu.pl
Karolak-Wojciechowska
Janina
J
Michalak
Barbara
B
Pekala
Elzbieta
E
Schumacher
Britta
B
Müller
Christa E
CE
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002855:Chromatography, Thin Layer; D003975:Diazepam / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008024:Ligands; D008297:Male; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014961:X-Ray Diffraction
D000927:Anticonvulsants; D058787:GABA-A Receptor Antagonists; D008024:Ligands; D011963:Receptors, GABA-A; D013843:Thiazines; D003975:Diazepam