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Our efforts lay emphasis on synthesis of S-aralkylated 5-(4-OMeC6H5)-4-phenyl-4H-1,2,4-triazol-3-thiols like pharmacologically active candidates to counter neurodegenerative disorder; Alzheimerand#39;s disease. A synthetic strategy was instigated by esterifying 4-methoxybenzoic acid through Fisher esterificationand#39;s methodology. Hydrazinolysis of corresponding ester was performed under reflux with methanolic hydrated hydrazine to afford 4-methoxybenzohydrazide (I) which refluxing with phenyl isothiocyanate (II) in MeOH to yield a reactive intermediate (III). The later underwent base-catalyzed intermolecular cyclization to furnish 5-(4-OMeC6H5)-4H-1,2,4-triazol-3-thiol (IV). Ultimately, IV was aralkylated at thiol position with aralkyl halides V(a-l) in polar aprotic solvent and catalytic amounts of LiH to provide S-aralkylated 5-(4- OMeC6H5)-4-phenyl-4H-1,2,4-triazol-3-thiols VI(a-l). Modern spectral analysis data explicitly established all the substitutions on nucleophilic S-atom of parent 1,2,4-triazol-3-thiol ring. Effective anti-cholinesterase potential depicted in 3-(phenylpropylthio)-5-(4-OMeC6H5)-4-phenyl-4H-1,2,4-triazole; VIc (IC50; 3.26and#177;0.35 μM) against acetyl cholinesterase; AChE and 3-(phenethylthio)-5-(4-OMeC6H5)-4-phenyl-4H-1,2,4-triazole; VIb (IC50; 8.52and#177;0.54 μM) against butyrylcholinesterase; BChE enzyme as compared to standard Eserine for both enzymes (IC50; 0.04and#177;0.01 μM). Molecular modelling analyses had been conducted to recognize the interconnection of these compounds with enzymes that suggested key interactions (Docking is made to untie the active binding sites). Anti-proliferative activity results showed VIg and VIj with -Cl groups on benzylic ring as promising candidates with HCT-116 cell viability of 14.83 % and 3.09 % respectively.

The goal of this work was to synthesize some 4-chloro-N-(dimethylphenyl)butamide regio-isomers starting from dimethylated phenylamines and to examine their biofilm inhibition against Staphylococcus aureus and Escherichia coli strains along with hemolytic activity. The synthetic approach for the synthesis of regio-isomers involved the reaction of 4-chlorobutanoyl chloride (1) with three different dimethylphenylamines (2a-c) in alkaline medium under vigorous shaking for 1-2 h under dynamic control of pH ranging from 9-10 to obtain the final products, 4-chloro-N-(dimethylphenyl)butamides (3a-c). The structural confirmation of these products was accomplished using IR, 1H-NMR, 13C-NMR and CHN analysis data.

In the present work, a series of {4-[(2-alkyloxy/aralkyloxy-3,5-dichlorophenyl)sulfonyl]-1-piperazinyl}(2-furyl)methanones was synthesized through a linear bi-step approach. The synthesis was initiated by the coupling of 2-furyl(1-piperazinyl)methanone (1) with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (2) under dynamic pH control in aqueous alkaline medium to form parent compound, {4-[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]-1-piperazinyl}(2-furyl)methanone (3). Then, the O-substitution reaction on nucleophile 3 was carried out by treating it with different alkyl/aralkyl halides (4a-l) in the presence of lithium hydride (LiH) and N,N-dimethylformamide (DMF) to obtained the designed {4-[(2-alkoxy/aralkyloxy-3,5-dichlorophenyl)sulfonyl]-1-piperazinyl}(2-furyl)methanones (5a-l). These synthesized compounds were screened against α-glucosidase enzyme and some of them exhibited considerable inhibitory activity. Additionally, compounds were also evaluated for hemolytic and cytotoxic profile.