3′-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1 H – and 2-propargyl-5-R-2 H -tetrazoles (R = H, Me, CH_{2}COOEt, CH_{2}CON(CH_{3})_{2}, Ph, 2-CH_{3}-C_{6}H_{4}, or 4-NO_{2}-C_{6}H_{4}) via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition to give 3′-modified thymidine analogs incorporating 1 H -1,2,3-triazolyl, 1 H -, and 2 H -tetrazolyl fragments in 41-76% yield. The structures of the obtained compounds have been elucidated by means of HRESI^{+}-MS, ^{1}H and ^{13} C{^{1}H} NMR, and single crystal X-ray diffraction {for 3′-[4-(1 H -5- N , N -dimethylaminocarbonylmethyltetrazol-1-yl)-1 H -1,2,3-triazol-1-yl]thymidine 10d }. In vitro biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1_{899A}. Moderate anti-influenza activity against influenza virus A/Puerto Rico/8/34 (H1N1) strain has been observed in the cases of 3′-(4-(1 H -tetrazol-1-ylmethyl)-1 H -1,2,3-triazol-1-yl)thymidine 10a (IC_{50} 39.6 μg/mL), 3′-(4-(2 H -5-ethoxycarbonyltetrazol-2-ylmethyl)-1 H -1,2,3-triazol-1-yl)thymidine 11c (IC_{50} 31.6 μg/mL), and 3′-(4-(2 H -5-(4-nitrophenyl)-tetrazol-2-ylmethyl)-1 H -1,2,3-triazol-1-yl)thymidine 11g (IC_{50} 46.4 μg/mL). The tested compounds possess very low cytotoxicity towards MDCK and MT4 cells as well as tumor human cervical carcinoma HeLa and promyelocytic leukemia HL-60 cells.
【저자키워드】 cytotoxicity, Thymidine analogs., tetrazole, 1,2,3-Triazole, 1D and 2D NMR spectroscopy, anti-influenza and anti-HIV activity, single crystal X-ray diffraction,