Synthesis and Biological Evaluation of Novel Thymidine Analogs Containing 1-1,2,3-Triazolyl, 1-Tetrazolyl, and 2-Tetrazolyl Fragments.

3'-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1- and 2-propargyl-5-R-2-tetrazoles (R = H, Me, CHCOOEt, CHCON(CH), Ph, 2-CH-CH, or 4-NO-CH) the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition to give 3'-modified thymidine analogs incorporating 1-1,2,3-triazolyl, 1-, and 2-tetrazolyl fragments in 41-76% yield. The structures of the obtained compounds have been elucidated by means of HRESI-MS, H and C{H} NMR, and single crystal X-ray diffraction {for 3'-[4-(1-5-,-dimethylaminocarbonylmethyltetrazol-1-yl)-1-1,2,3-triazol-1-yl]thymidine }. biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1.

Tetrazole Derivatives as Promising Anticancer Agents.

Tetrazole cycle is a promising pharmacophore fragment frequently used in the development of novel drugs. This moiety is a stable, practically non-metabolized bioisosteric analog of carboxylic, cis-amide, and other functional groups. Over recent 10-15 years, various isomeric forms of tetrazole (NH-unsubstituted, 1H-1- substituted, and 2H-2-substituted tetrazoles) have been successfully used in the design of promising anticancer drugs.