3'-azido-3'-deoxy-3-(2,3-epoxypropyl)thymidine | 142644-46-0

• 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-3-(2,3-epoxypropyl)thymidine
• 英文别名: 3-glycidyl-3'-azido-3'-deoxythymidine；1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-methyl-3-(oxiran-2-ylmethyl)pyrimidine-2,4-dione；1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-3-(oxiran-2-ylmethyl)pyrimidine-2,4-dione
• CAS: 142644-46-0
• 化学式: C₁₃H₁₇N₅O₅
• 分子量: 323.308
• InChiKey: VXSOMEACKFVTFQ-NVEZCULWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  97
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3'-azido-3'-deoxy-3-(2,3-epoxypropyl)thymidine 在 水 作用下， 生成 1-((2R,4S,5S)-4-Azido-5-hydroxymethyl-tetrahydro-furan-2-yl)-3-(2,3-dihydroxy-propyl)-5-methyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

  摘要：

  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.

  DOI：

  10.1021/jm9600095
• 作为产物：
  描述：

  齐多夫定 、 环氧溴丙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以37%的产率得到3'-azido-3'-deoxy-3-(2,3-epoxypropyl)thymidine
  参考文献：
  名称：

  Synthesis and Anti-human Immunodeficiency Virus Type 1(HIV-1) Activity of 3-Substituted Derivatives of 3'-Azido-3'-deoxythymidine (AZT), and Inhibition of HIV-1 Reverse Transcriptase by Their 5'-Triphosphates.

  摘要：

  通过 3'-azido-3'-deoxythymidine (1)、AZT 与 N, N-二甲基甲酰胺二烷基缩醛或烷基溴在碱存在下的反应，制备了各种 3 取代的 3'-azido-3'-deoxythymidine 类似物（2a-i），并评估了它们对人类免疫缺陷病毒 1 型（HIV-1）的活性。为了研究对 HIV-1 逆转录酶活性的抑制作用，还合成了相应的 5'-三磷酸类似物（9）。超出预期的是，一些 AZT 的 N3 衍生物在一定程度上保留了抗 HIV-1 的活性。在获得的化合物（2a-i）中，3-烯丙基-AZT（2e）对 MT-4 细胞中 HIV-1 的体外复制最有效，EC50 值为 0.9μM。然而，3-烯丙基-AZT 5'-三磷酸酯（9e）对 HIV-1 逆转录酶活性没有抑制作用。

  DOI：

  10.1248/cpb.40.920

文献信息

• Synthesis and Anti-human Immunodeficiency Virus Type 1(HIV-1) Activity of 3-Substituted Derivatives of 3'-Azido-3'-deoxythymidine (AZT), and Inhibition of HIV-1 Reverse Transcriptase by Their 5'-Triphosphates.
  作者：Yukio KITADE、Akiyuki SUZUKI、Kosaku HIROTA、Yoshifumi MAKI、Hideo NAKANE、Katsuhiko ONO、Masanori BABA、Shiro SHIGETA

  DOI：10.1248/cpb.40.920

  日期：——

  Various 3-substituted 3'-azido-3'-deoxythymidine analogs (2a-i) were prepared by the reaction of 3'-azido-3'-deoxythymidine (1), AZT with N, N-dimethylformamide dialkylacetal or alkyl bromide in the presence of base and their activities against human-immunodeficiency virus type-1 (HIV-1) were evaluated. The corresponding 5'-triphosphate analogs (9) were also synthesized in order to examine inhibition of HIV-1 reverse transcriptase activity. Beyond expectation, some N3-derivatives of AZT were found to reserve the anti-HIV-1 activity to some extent. Among the compounds (2a-i) obtained, 3-allyl-AZT (2e) was the most active against HIV-1 replication in MT-4 cells in vitro with an EC50 value of 0.9μM. 3-Allyl-AZT 5'-triphosphate (9e), however, exhibited no inhibition of HIV-1 reverse transcriptase activity.

  通过 3'-azido-3'-deoxythymidine (1)、AZT 与 N, N-二甲基甲酰胺二烷基缩醛或烷基溴在碱存在下的反应，制备了各种 3 取代的 3'-azido-3'-deoxythymidine 类似物（2a-i），并评估了它们对人类免疫缺陷病毒 1 型（HIV-1）的活性。为了研究对 HIV-1 逆转录酶活性的抑制作用，还合成了相应的 5'-三磷酸类似物（9）。超出预期的是，一些 AZT 的 N3 衍生物在一定程度上保留了抗 HIV-1 的活性。在获得的化合物（2a-i）中，3-烯丙基-AZT（2e）对 MT-4 细胞中 HIV-1 的体外复制最有效，EC50 值为 0.9μM。然而，3-烯丙基-AZT 5'-三磷酸酯（9e）对 HIV-1 逆转录酶活性没有抑制作用。
• 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.