Rapid Parallel Synthesis of Combinatorial Libraries of Substituted 3-Thio-1,2,4-triazoles and 2-Thioimidazoles

Abstract

Combinatorial libraries of substituted 3-thio-1,2,4-triazoles and 2-thioimidazoles were synthesized in good yield by alkylation of the products via the reaction of isothiocyanates and carboxylic acid hydrazides or beta-aminoketones, respectively. A total of 275 3-thio-1,2,4-triazoles and 283 2-thioimidazoles were synthesized out of the attempted 288 in each case. Most the yields were between 45% and 98%, and all the compounds synthesized were purified to >85% purity. Variations in yields revealed no definitive trends and were mainly attributed to bulky alkylating agents used and the plate well location of the reaction mixtures.

Five‐Membered Heterocycles with Three Heteroatoms: Triazoles

“…For example, reactions of acylhydrazines with isothiocyanates or isocyanates to give 1,2,4-triazoles can be seen in the following examples. Acylhydrazines 134 and isothiocyanates 135 afforded 1,2,4-triazole-3-thiones 136, which were intercepted by alkyl halides to give substituted 3-thio-1,2,4-triazoles 137 (Scheme 12.42) [196]. Solid-supported acylhydrazines 138 react with isocyanates or isothiocyanates followed by base-induced cyclization/ cleavage to provide 1,2,4-trisubstituted urazoles and thiourazoles 139 (Scheme 12.43) [197].…”

Design, synthesis and SAR exploration of tri-substituted 1,2,4-triazoles as inhibitors of the annexin A2–S100A10 protein interaction

“…Finally, the target 5-methyl-1,2,4-triazoles 62 – 66 were prepared by reacting substituted 3-mercapto-5-methyl-1,2,4-triazoles 58 – 60 with chloro- N -aryl-acetamides 61 in the presence of potassium carbonate as a base in DMF. 23–33 …”

Simple modifications to methimazole that enhance its inhibitory effect on tumor necrosis factor-α-induced vascular cell adhesion molecule-1 expression by human endothelial cells

“…MMI was obtained from Sigma (St. Louis, MO). 1a and 1b were prepared according to reported procedures (Kohn et al, 2011; Theoclitou et al, 2002). Compounds 2a and 2b were prepared by the method reported by Gan et al (Gan et al, 2010).…”