$S$-substituted derivatives of 1,2,4-triazol-3-thiol as new drug candidates for type II diabetes

摘要

The therapeutic applications of 1,2,4-triazoles motivated us to synthesize some new derivatives. Two series of $S$-substituted derivatives (8a-8j, 12a-12i ) of 5-${$1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl$}$-4-phenyl-4$H$-1,2,4-triazol-3-thiol (6 ) have been synthesized and evaluated for their biological potential. Using 4-chlorobenzene sulfonyl chloride (1 ) and ethyl piperidine-3-carboxylate (2 ), ethyl 1-[(4-chlorophenyl)sulfonyl]piperidine-3-carboxylate (3 ) was synthesized and converted into 3,4,5-trisubstituted 1,2,4-triazole (6 ) through formation of the corresponding carbohydrazide (4 ) and hydrazinecarbothioamide (5 ). Compound 6 was transformed into 8a-8j by alkyl halides (7a-7j ) and into 12a-12i by $N$-aralkyl/aryl-2-bromoacetamides (11a-11i ) in an aprotic solvent. The electrophiles, 11a-11i , were synthesized by gearing up $N$-substituted aralkyl/aryl amines (10a-10i ) with 2-bromoacetyl bromide (9 ) under dynamic pH control by aqueous sodium carbonate. Structures were elucidated through the spectral techniques of IR, EIMS, $^{1}$H NMR, and $^{13}$C NMR. Most of the synthesized derivatives were found to be potent inhibitors of $lpha $-glucosidase enzyme and even better than acarbose. Acarbose is a reference standard and is a commercially available $lpha $-glucosidase inhibitor to treat patients with type II diabetes. The low hemolytic activity also emphasized the potential of the synthesized compounds as new drug candidates.