Synthesis And Biological Evaluation Of Novel Triazole Derivatives

More than 90% population of the world is infected with a herpesvirus. The 1,2,3-triazole moiety shows diverse biological activities. Three series of novel 1,2,3-triazoles were designed and synthesized for anti-HCMV and VZV. More than 120 novel compounds including 70 target compounds were synthesized via multi step reaction, all of them were characterized by ¹H NMR, ¹³ C NMR and HRMS.A series of 5-（benzylthio）-4-（N-phenyl carbamyl）-1H-1,2,3-triazoles were designed and synthesized. Twenty target compounds were obtained starting from sodium azide in 7 steps with an overall yield of 11%-29%. 5-Iodo-1,2,3-triazole was synthesized successfully using a novel CuI / NBS catalytic system via the Huisgen 1,3-dipolar cycloaddition. Treated the 5-iodo-1,2,3-triazole with sulfur and 4-substituted benzyl bromides through a one-pot procedure containing three steps to afford 5-（benzylthio）-1,2,3-triazoles. All the target compounds showed significant antiviral activities against HCMV and VZV, part of them even more effective than the positive drug. These novel 1,2,3-triazoles exhibited moderate activity toward Hela and MCF-7 cell lines and weak activity toward A549 cell line.An thioacetamide linker was introduced to modified the structure of the target compounds in last chapter, which was successfully linked with the 1,2,3-triazole moiety by treating the 5-iodo-1,2,3-triazole with sulfur and 2-bromo-N-phenylacetamides via a one-pot procedure containing three steps. Then a series of novel 5-thioacetaniline-4-（N-phenyl carbamyl）-1H-1,2,3-triazoles were synthesized with an overall yield of 10%-26% in 8 steps.A series of novel 4-carbamyl-1,5-diaryl-1,2,3-triazoles were designed and synthesized. Utilized intermediates in the first two chapters though amidation reaction to prepare 30 target compounds. These compounds showed weak to moderate anticancer activity against four human cancer cell lines and part of them also exhibited weak antiviral activity against HCMV and VZV.