Design, synthesis, molecular docking, ADMET studies, and biological activity evaluation of new 2-({[3-aryl-1,2,4-oxadiazol-5-yl)methyl]thio}-1H-benzimidazoles and 6-amino-6-aryl-5,6-dihydro[1,6,2,4]oxathiadiazocino[4,5-a]benzimidazol-3(2H)-ones

•New series of 1H-benzimidazoles have been successfully synthesized.•Unexpected products 6-amino-6-aryl-5,6-dihydro[1,6,2,4]oxathiadiazocino[4,5-a]benzimidazol-3(2H)-one 6a-c were formed and well characterized.•The synthesized compounds are promising candidates as novel hypolipidemic derivatives and anti-atherosclerotic.•The obtained biological results showed that the investigated compounds have a positive drug-likeness profile. Aryl amidoximes are active binucleophilic compounds used as a powerful and versatile reagent in synthesizing diverse heterocyclic compounds with pharmacological interest. Thus, a new series of 2-({[3-aryl-1,2,4-oxadiazol-5-yl)methyl]thio}-1H-benzimidazoles 5a-g was successfully synthesized from the reaction of (1,3-benzimidazol-2-ylthio)acetic acid (2) with aryl amidoximes 4a-g, respectively. The reaction is proceeded in dimethylformamide (DMF) in the presence of 1,1′-carbonyldiimidazole (CDI) as a coupling reagent. The unexpected products 6-amino-6-aryl-5,6-dihydro[1,6,2,4]oxathiadiazocino[4,5-a]benzimidazol-3(2H)-one 6a-c were formed through the reaction of acetic acid derivative 2 with arylamidoxime 4b,c,g in acetonitrile at room temperature or under reflux, using CDI as coupling reagent. Compounds 5g and 6a proved the most potent hypocholesterolemic agents, with significant hypolipidemic and hypotriglyceridemic influence. They represent promising candidates for establishing novel hypolipidemic derivatives and anti-atherosclerotic. Compounds 5g and 6a demonstrated the highest antioxidant effect, reaching 77 and 81% radical scavenging activity, respectively. Docking studies were also performed on the synthesized members to examine their binding interactions with their target enzyme, Niemann-Pick C1-like 1 (NPC1L1). Finally, physicochemical properties of the synthesized compounds were investigated in silico. The obtained results showed that most synthesized members had a positive drug-likeness profile. [Display omitted]