5β-cholanic acid-3,7,12-trione 3'-azido-3'-deoxythymidin-5'-yl ester

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 5β-cholanic acid-3,7,12-trione 3'-azido-3'-deoxythymidin-5'-yl ester
• 英文别名: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl (4R)-4-[(5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3,7,12-trioxo-1,2,4,5,6,8,9,11,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]pentanoate；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl (4R)-4-[(5S,8R,9S,10S,13R,14S,17R)-10,13-dimethyl-3,7,12-trioxo-1,2,4,5,6,8,9,11,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]pentanoate
• 化学式: C₃₄H₄₅N₅O₈
• 分子量: 651.76
• InChiKey: VBLBGWMBPOFBJZ-UTRVAGTOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  47
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  151
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  去氢胆酸 、 齐多夫定 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以78%的产率得到5β-cholanic acid-3,7,12-trione 3'-azido-3'-deoxythymidin-5'-yl ester
  参考文献：
  名称：

  New Azt Conjugates as Potent Anti-HIV Agents

  摘要：

  In an attempt to discover anti-HIV agents with much reduced cytotoxicity from the currently available HIV-reverse transcriptase inhibitors, AZT conjugates of cholanic acids, 2-imidazolidone-4- carboxylic acid and its derivatives, and N, N'-disubstituted 5-hydroxy-tetrahydropyrimidin-2-ones have been synthesized and their anti-HIV profiles determined with CEM-SS cell line. The AZT conjugates with 2-imidazolidone-4- carboxylic acid and 2-pyrrolidone-5-carboxylic acid through an ester linkage, and with N,N'-diphenyl-5-hydroxy-tetrahydropyrimidin-2-one through a succinate tether showed significantly higher therapeutic indexes than AZT while they also retained or enhanced AZT's anti-HIV activity. Thus, structural features that favor the desired therapeutic profile of the conjugates appear to include a five-membered ring cyclic urea or lactam, and six-membered ring cyclic urea with N,N'-diphenyl substitution.

  DOI：

  10.1080/15257770500377789

文献信息

• New Azt Conjugates as Potent Anti-HIV Agents
  作者：Zhengqing You、Henry Joung Lee

  DOI：10.1080/15257770500377789

  日期：2006.1

  In an attempt to discover anti-HIV agents with much reduced cytotoxicity from the currently available HIV-reverse transcriptase inhibitors, AZT conjugates of cholanic acids, 2-imidazolidone-4- carboxylic acid and its derivatives, and N, N'-disubstituted 5-hydroxy-tetrahydropyrimidin-2-ones have been synthesized and their anti-HIV profiles determined with CEM-SS cell line. The AZT conjugates with 2-imidazolidone-4- carboxylic acid and 2-pyrrolidone-5-carboxylic acid through an ester linkage, and with N,N'-diphenyl-5-hydroxy-tetrahydropyrimidin-2-one through a succinate tether showed significantly higher therapeutic indexes than AZT while they also retained or enhanced AZT's anti-HIV activity. Thus, structural features that favor the desired therapeutic profile of the conjugates appear to include a five-membered ring cyclic urea or lactam, and six-membered ring cyclic urea with N,N'-diphenyl substitution.