3'-azido-3'-deoxy-5'-O-thexyldimethylsilylthymidine | 123533-06-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3'-azido-3'-deoxy-5'-O-thexyldimethylsilylthymidine
• 英文别名: 5'-O-thexyldimethylsilyl-3'-azido-3'-deoxythymidine；5'-O-thexyldimethylsilyl AZT；1-[(2R,4S,5S)-4-azido-5-[[2,3-dimethylbutan-2-yl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 123533-06-2
• 化学式: C₁₈H₃₁N₅O₄Si
• 分子量: 409.561
• InChiKey: ZXUZLQLMSPWYNR-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.47
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  82.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3'-azido-3'-deoxy-5'-O-thexyldimethylsilylthymidine 在 Dowex 50(H+) 作用下， 以 甲醇 为溶剂， 生成 齐多夫定
  参考文献：
  名称：

  3'-取代-2'，3'-二脱氧核苷类似物的合成作为潜在的抗抑郁药

  摘要：

  3'-氨基-3'-脱氧胸苷分六个步骤制备，胸腺嘧啶核苷的总收率为67％。五个衍生品和复合他们的抗HIV活性进行了测试。

  DOI：

  10.1016/s0040-4039(00)99623-0
• 作为产物：
  描述：

  [(2R,3S,5R)-2-[[2,3-dimethylbutan-2-yl(dimethyl)silyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] methanesulfonate 在 sodium azide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3'-azido-3'-deoxy-5'-O-thexyldimethylsilylthymidine
  参考文献：
  名称：

  3'-取代-2'，3'-二脱氧核苷类似物的合成作为潜在的抗抑郁药

  摘要：

  3'-氨基-3'-脱氧胸苷分六个步骤制备，胸腺嘧啶核苷的总收率为67％。五个衍生品和复合他们的抗HIV活性进行了测试。

  DOI：

  10.1016/s0040-4039(00)99623-0

文献信息

• Ether, Carbonate and Urethane Deoxynucleoside Derivatives as Prodrugs.
  作者：Kristin Hammer、Jostein Hatlelid、Morten Grøtli、Joseph Arukwe、Jo Klaveness、Frode Rise、Kjell Undheim、Connie N. Rosendahl、Monika Haugg、Nathalie Trabesinger-Rüf、Elmar G. Weinhold

  DOI：10.3891/acta.chem.scand.50-0609

  日期：——

  3'-Deoxythymidine and its 3'-azido derivative, 2',3'-dideoxycytidine, 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine have been acylated to form carbonates and methanes in chemoselective reactions. The nucleosides have been N- and/or O-alkylated by alpha-chloroethyl or chloromethyl alkyl carbonates to form alpha-alkyloxycarbonyloxyethyl or alkyloxycarbonyloxymethyl derivatives. The products are lipophilic in order to facilitate transport through biological membranes and are designed to be cleaved by esterases with liberation of the bioactive nucleoside. Initial esterase cleavage of the alkylated derivatives produces hemiacetals or -aminals which subsequently dissociate to the active nucleoside.
• Synthesis and Evaluation of “AZT-HEPT”, “AZT-Pyridinone”, and “ddC-HEPT” Conjugates as Inhibitors of HIV Reverse Transcriptase
  作者：Renée Pontikis、Valérie Dollé、Jean Guillaumel、Elsa Dechaux、Reine Note、Chi Hung Nguyen、Michel Legraverend、Emile Bisagni、Anne-Marie Aubertin、David S. Grierson、Claude Monneret

  DOI：10.1021/jm991125l

  日期：2000.5.1

  To test the concept that HIV reverse transcriptase could be effectively inhibited by "mixed site inhibitors", a series of seven conjugates containing both a nucleoside analogue component(AZT 1, ddC 2) and a nonnucleoside type inhibitor (HEPT analogue 12, pyridinone 27) were synthesized and evaluated for their ability to block HIV replication. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 mu M anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. The (C-5)AZT-pyridinone conjugates 34-37 were found to be inactive. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC50 = 0.45 mu M) against HTV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. No synergistic effect was-observed for these bis-substrate inhibitors, suggesting that the two individual inhibitor components in these molecules do not bind simultaneously in their respective sites. Interestingly, however, the results indicate that the AZT-HEPT conjugates and the ddC-HEPT derivative 26 inhibit reverse transcriptase (RT) in an opposite manner. One explanation for this difference is that the former compounds interact preferentially with the hydrophobic pocket in RT, whereas 26 (after supposed triphosphorylation) inhibits RT through binding in the catalytic site.
• Synthesis and evaluation of new 2′,3′-dideoxynucleoside analogs as potential anti-AIDS and anti-herpes drugs
  作者：A Faraj、M Maillard、M Lemaître、S Letellier、F Frappier、JC Florent、DS Grierson、C Monneret、A Zerial

  DOI：10.1016/0223-5234(92)90102-7

  日期：1992.3

  Based on the known structure-activity relationships for the active anti-HIV, a series of 3'-deoxy-3'-N-functionalized thymidine analogs has been synthesized from thymidine. Evaluation for inhibitory activity against human immunodeficiency virus (HIV) replication in CEM cells and against herpes simplex virus in MRC-5 cells is reported.
• Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs
  作者：David R. Adams、Caroline Perez、Michel Maillard、Jean-Claude Florent、Michel Evers、Yvette Hénin、Simon Litvak、Laura Litvak、Claude Monneret、David S. Grierson

  DOI：10.1021/jm9600095

  日期：1997.5.1

  A series of 22 derivatives of AZT substituted at the N-3 position of the thymine base were prepared and evaluated for anti-HIV activity in cell culture (Lai strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent displayed activities in the 0.045-0.082 mu M range. The analogs 12d, 12e, 12q, 15, and 19 were active at <0.5 mu M concentration. Compound 18 in which two molecules of AZT are connected at N-3 via a two-carbon link and ''dimer'' II also displayed significant; activity. To obtain information concerning the mechanism of RT inhibition by these AZT analogs, compounds 7, 12d, 12e, and 12q were incubated with recombinant HIV-1 RT in the presence of poly(A)-oligo[dT((12-18))] and poly(C)-oligo[dG((12-18))] template-primers. In contrast to AZT-TP (control), none of these nucleosides displayed any significant inhibition of RT in the recombinant enzyme assay, indicating that phosphorylation is a necessary prerequiste for activity.
• Synthesis of 3′-substituted-2′,3′-dideoxynucleoside analogs as potential anti-aids drugs
  作者：Michel Maillard、Abdesslem Faraj、François Frappier、Jean-Claude Florent、David S. Grierson、Claude Monneret

  DOI：10.1016/s0040-4039(00)99623-0

  日期：1989.1

  3′-Amino-3′-deoxythymidine was prepared in six steps and in 67% overall yield from thymidine. Five derivatives of and compound were tested for their anti-HIV activity.

  3'-氨基-3'-脱氧胸苷分六个步骤制备，胸腺嘧啶核苷的总收率为67％。五个衍生品和复合他们的抗HIV活性进行了测试。