Green synthesis, molecular docking and pharmacological evaluation of new triazolo‐thiadiazepinylcoumarine derivatives as sedative‐hypnotic scaffold

Abstract

Abstract 4‐Amino‐5‐mercapto‐4 H ‐1,2,4‐triazole derivative 1 was used as a key intermediate for the preparation of 1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazepine derivatives 5a‐d , 12a‐g , and 16 via reactions with the appropriate chalcones 2a‐d , α,β‐unsaturated carbonitrile derivatives 9a‐g and 13 , respectively. The identity of the synthesized compounds was elucidated via their spectral data and elemental analysis. Moreover, the sedative‐hypnotic activity of the newly synthesized compounds were evaluated and showed excellent activities especially compounds 12b , 12f , and 16 . Also, their structure activity relationship (SAR) was clearly demonstrated and showed that the electron‐donating groups enhance activities while electron‐withdrawing groups decrease activities. The molecular docking of the most active derivative 16 against γ‐amino butyric acid (GABA) receptor was performed by the MOE 2014 0901program. The acquired outcomes demonstrated that the most active compounds could be a helpful model for future structure, adjustment, and examination to build more active analogs.