(+)-(S)-4,5,6,7-tetrahydro-8-(hexaethylene glycol)-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk][1,4]benzodiazepine-2(1H)-thione | 1425581-52-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (+)-(S)-4,5,6,7-tetrahydro-8-(hexaethylene glycol)-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk][1,4]benzodiazepine-2(1H)-thione
• 英文别名: (11S)-7-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-11-methyl-10-(3-methylbut-2-enyl)-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4(13),5,7-triene-2-thione
• CAS: 1425581-52-7
• 化学式: C₂₈H₄₅N₃O₇S
• 分子量: 567.747
• InChiKey: YXKXCYFCMQVYGK-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  39
• 可旋转键数：
  20
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (+)-(S)-4,5,6,7-tetrahydro-8-(hexaethylene glycol)-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk][1,4]benzodiazepine-2(1H)-thione 在 4-二甲氨基吡啶 、 四丁基氟化铵 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 苯 为溶剂， 反应 81.0h， 生成 2-[2-[2-[2-[2-[2-[[(11S)-11-methyl-10-(3-methylbut-2-enyl)-2-sulfanylidene-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4(13),5,7-trien-7-yl]oxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl 3-[1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,4-dioxopyrimidin-5-yl]propanoate
  参考文献：
  名称：

  Bifunctional inhibition of HIV-1 reverse transcriptase: A first step in designing a bifunctional triphosphate

  摘要：

  The onset of resistance to approved anti-AIDS drugs by HIV necessitates the search for novel inhibitors of HIV-1 reverse transcriptase (RT). Developing single molecular agents concurrently occupying the nucleoside and nonnucleoside binding sites in RT is an intriguing idea but the proof of concept has so far been elusive. As a first step, we describe molecular modeling to guide focused chemical syntheses of conjugates having nucleoside (d4T) and nonnucleoside (TIBO) moieties tethered by a flexible polyethylene glycol (PEG) linker. A triphosphate of d4T-6PEG-TIBO conjugate was successfully synthesized that is recognized as a substrate by HIV-1 RT and incorporated into a double-stranded DNA. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.015
• 作为产物：
  描述：

  六甘醇 在 platinum(IV) oxide 、 氢气 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 31.83h， 生成 (+)-(S)-4,5,6,7-tetrahydro-8-(hexaethylene glycol)-5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk][1,4]benzodiazepine-2(1H)-thione
  参考文献：
  名称：

  Bifunctional inhibition of HIV-1 reverse transcriptase: A first step in designing a bifunctional triphosphate

  摘要：

  The onset of resistance to approved anti-AIDS drugs by HIV necessitates the search for novel inhibitors of HIV-1 reverse transcriptase (RT). Developing single molecular agents concurrently occupying the nucleoside and nonnucleoside binding sites in RT is an intriguing idea but the proof of concept has so far been elusive. As a first step, we describe molecular modeling to guide focused chemical syntheses of conjugates having nucleoside (d4T) and nonnucleoside (TIBO) moieties tethered by a flexible polyethylene glycol (PEG) linker. A triphosphate of d4T-6PEG-TIBO conjugate was successfully synthesized that is recognized as a substrate by HIV-1 RT and incorporated into a double-stranded DNA. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.015

文献信息

• Bifunctional inhibition of HIV-1 reverse transcriptase: A first step in designing a bifunctional triphosphate
  作者：Dongyuan Piao、Aravind Basavapathruni、Pinar Iyidogan、Guangxiu Dai、Wolfgang Hinz、Adrian S. Ray、Eisuke Murakami、Joy Y. Feng、Fei You、Ginger E. Dutschman、David J. Austin、Kathlyn A. Parker、Karen S. Anderson

  DOI：10.1016/j.bmcl.2012.12.015

  日期：2013.3

  The onset of resistance to approved anti-AIDS drugs by HIV necessitates the search for novel inhibitors of HIV-1 reverse transcriptase (RT). Developing single molecular agents concurrently occupying the nucleoside and nonnucleoside binding sites in RT is an intriguing idea but the proof of concept has so far been elusive. As a first step, we describe molecular modeling to guide focused chemical syntheses of conjugates having nucleoside (d4T) and nonnucleoside (TIBO) moieties tethered by a flexible polyethylene glycol (PEG) linker. A triphosphate of d4T-6PEG-TIBO conjugate was successfully synthesized that is recognized as a substrate by HIV-1 RT and incorporated into a double-stranded DNA. (c) 2013 Elsevier Ltd. All rights reserved.