Synthesis and In Vitro Evaluation of Novel Acyclic and Cyclic Nucleoside Analogs with a Thiadiazole Ring

Abstract

The synthesis of six thiadiazole nucleoside analogs is reported: 5-diacetylamino-1,2,4-thiadiazol-3-one (1), 5-amino-2- (tetrahydrofuran-2-yl)-1,2,4-thiadiazol-3-one (2), 5-amino-3-[(2′-hydroxyethoxy)methyl]-1,3,4-thiadiazol-2-one (3), 5-amino-3-(4′-hydroxy-2′-hydroxymethyl-butyl)-1,3,4-thiadiazole-2-thione (4), (R)-5-amino-3-(2′,3′-dihydroxypropyl)-1,3,4-thiadiazole-2-thione (5), and (S)-5-amino-3-(2′,3′-dihydroxypropyl)-1,3,4-thiadiazole-2-thione (6). The synthesis, characterization, and properties of these new synthesized thiadiazole derivatives are discussed. A dimerization of 5-amino-3H-1,3,4-thiadiazole-2-thione (14) by sodium nitrite resulting in di-(5-amino-1,3,4-thiadiazol-2-yl) disulfide (19) is also reported. The preliminary in vitro evaluation of these newly synthesized compounds is discussed.

Electrochemical study of 2-amino-5-mercapto-1,3,4-thiadiazole in the absence and presence ofp-benzoquinone: an efficient strategy for the electrosynthesis of new 1,3,4-thiadiazole derivatives

“…In the meantime, the formation of a thin yellowish layer on the carbon anodes attracted our attention. On account of this observation, because of the color, solubility, and melting point difference of the yellowish film and gray powder of ATB, 18 we supposed that this yellowish layer on the surface of anodes might be the AMT dimer or polymer (the idea has come from the high potential of AMT in the polymerization). 26 Subsequently, the electrolysis process of AMT was also performed individually under similar conditions of ATB synthesis procedure ( Scheme 5 ).…”

“…Consistent with the significant data displayed by voltammograms, we first involved AMT in a Michael-type addition reaction with p -BQ to synthesis 2-((5-amino-1,3,4-thiadiazol-2-yl)thio)benzene-1,4-diol ( ATB ), and then during our electrochemical study, the oxidized structure of AMT showed its great potential as a radical specie; thus, for the first time ever, we propose a green electrochemical protocol for the production of AMT dimer (Scheme 1), which was chemically synthesized before by different research groups. 18,19…”

“…Consistent with the signicant data displayed by voltammograms, we rst involved AMT in a Michael-type addition reaction with p-BQ to synthesis 2-((5-amino-1,3,4-thiadiazol-2-yl)thio)benzene-1,4diol (ATB), and then during our electrochemical study, the oxidized structure of AMT showed its great potential as a radical specie; thus, for the rst time ever, we propose a green electrochemical protocol for the production of AMT dimer (Scheme 1), which was chemically synthesized before by different research groups. 18,19 For medicinal purposes, in the last section of this study, we used an in silico method to assess the biological activity of the electrosynthesized compounds. By using this method, the conditions for new 1,3,4-thiadiazole derivatives will be examined to manufacture drugs in the future.…”