Synthesis and docking study on thiadiazolo[3,2-a][1,3]diazepin-8(5H)-one derivatives as selective GABA(A) agonists

HIE-124 is a new member of ultra-short acting hypnotics’ drug family. In this research, the synthesis ofanalogues of HIE-124 drug in the heterocyclic thiazole ring replaced to thiadiazole, will be presented.Thiadiazolodiazepines during a two-step reaction starting from the amino thiadiazole resultedfrom-various derivatives of benzoic acid and thiosemicarbazide were synthesized. In the first step, thereaction of synthetic raw material 2-amino thiadiazole and 4-chlorobutyrilchloride in toluene solventgive the 4-chloro-N-(5-(methyl/aryl)-1,3,4-thiadiazol-2-yl) butanamide intermediate. In the nextstep, from the cyclization reaction of this intermediate ring in the presence of base under reflux, thetarget products are synthesized. Structure of products was identified based on IR, HNMR and CNMRspectroscopy analysis. Then, the procedure of docking of ligands were performed on the activesite of GABAA that the common residues involved in allosteric modulators such as benzodiazepinesand HIE-124 include ASN82, ASN81, PHE79, MET1, TYR106, ALA38 and AlA168. Consequently,These Docking calculations suggest that these new compounds might be having better interactionresults between receptor (GABAA) than HIE-124.