3-(2-bromoethyl)-3'-azido-3'-deoxy-5'-O-(tert-butyldimethylsilyl)thymidine | 189145-25-3

• 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-(2-bromoethyl)-3'-azido-3'-deoxy-5'-O-(tert-butyldimethylsilyl)thymidine
• 英文别名: 1-[(2R,4S,5S)-4-azido-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-3-(2-bromoethyl)-5-methylpyrimidine-2,4-dione
• CAS: 189145-25-3
• 化学式: C₁₈H₃₀BrN₅O₄Si
• 分子量: 488.457
• InChiKey: BNOJBEXKQMUNTJ-RRFJBIMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  73.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(2-bromoethyl)-3'-azido-3'-deoxy-5'-O-(tert-butyldimethylsilyl)thymidine 在 4 A molecular sieve 、 氢氟酸 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 25.0h， 生成 3-[(3'''-azido-3'''-deoxythymidin-3''-yl)ethyl]-3'-azido-3'-deoxythymidine
  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 在 咪唑 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 3-(2-bromoethyl)-3'-azido-3'-deoxy-5'-O-(tert-butyldimethylsilyl)thymidine
  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

文献信息

• 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.