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

Authors : Aziz Ur REHMAN, Khadija NAFEESA, Muhammad Athar ABBASI, Sabahat Zahra SADDIQUI, Shahid RASOOL, Syed Adnan Ali SHAH, Muhammad ASHRAF, Muhammad Arif LODHI, Farman Ali KHAN, Bakht JAHAN

Pages : 652-671

View : 22 | Download : 8

Publication Date : 0000-00-00

Article Type : Research Paper

Abstract :The therapeutic applications of 1,2,4-triazoles motivated us to synthesize some new derivatives. Two series of $S$-substituted derivatives insert ignore into journalissuearticles values(8a-8j, 12a-12i); of 5-$\{$1-[insert ignore into journalissuearticles values(4-chlorophenyl);sulfonyl]-3-piperidinyl$\}$-4-phenyl-4$H$-1,2,4-triazol-3-thiol insert ignore into journalissuearticles values(6); have been synthesized and evaluated for their biological potential. Using 4-chlorobenzene sulfonyl chloride insert ignore into journalissuearticles values(1); and ethyl piperidine-3-carboxylate insert ignore into journalissuearticles values(2);, ethyl 1-[insert ignore into journalissuearticles values(4-chlorophenyl);sulfonyl]piperidine-3-carboxylate insert ignore into journalissuearticles values(3); was synthesized and converted into 3,4,5-trisubstituted 1,2,4-triazole insert ignore into journalissuearticles values(6); through formation of the corresponding carbohydrazide insert ignore into journalissuearticles values(4); and hydrazinecarbothioamide insert ignore into journalissuearticles values(5);. Compound 6 was transformed into 8a-8j by alkyl halides insert ignore into journalissuearticles values(7a-7j); and into 12a-12i by $N$-aralkyl/aryl-2-bromoacetamides insert ignore into journalissuearticles values(11a-11i); in an aprotic solvent. The electrophiles, 11a-11i, were synthesized by gearing up $N$-substituted aralkyl/aryl amines insert ignore into journalissuearticles values(10a-10i); with 2-bromoacetyl bromide insert ignore into journalissuearticles values(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 $\alpha $-glucosidase enzyme and even better than acarbose. Acarbose is a reference standard and is a commercially available $\alpha $-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.
Keywords : 1, 2, 4 Triazole, sulfonamides, anti alpha glucosidase, hemolytic activity