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

Document Type: Original Article

Authors

Department of Chemistry, School of Basic-Science, University of Imam Hossein, Tehran, Iran

Abstract

HIE-124 is a new member of ultra-short acting hypnotics’ drug family. In this research, the synthesis of
analogues 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 resulted
from-various derivatives of benzoic acid and thiosemicarbazide were synthesized. In the first step, the
reaction of synthetic raw material 2-amino thiadiazole and 4-chlorobutyrilchloride in toluene solvent
give the 4-chloro-N-(5-(methyl/aryl)-1,3,4-thiadiazol-2-yl) butanamide intermediate. In the next
step, from the cyclization reaction of this intermediate ring in the presence of base under reflux, the
target products are synthesized. Structure of products was identified based on IR, HNMR and CNMR
spectroscopy analysis. Then, the procedure of docking of ligands were performed on the active
site of GABAA that the common residues involved in allosteric modulators such as benzodiazepines
and HIE-124 include ASN82, ASN81, PHE79, MET1, TYR106, ALA38 and AlA168. Consequently,
These Docking calculations suggest that these new compounds might be having better interaction
results between receptor (GABAA) than HIE-124.

Keywords

Main Subjects