(2S,3S,4S,5S)-6-cyclohexyl-2,5-bis(dibenzylamino)-1-phenylhexane-3,4-diol | 1011256-27-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3S,4S,5S)-6-cyclohexyl-2,5-bis(dibenzylamino)-1-phenylhexane-3,4-diol
• 英文别名: (2S,3S,4S,5S)-1-cyclohexyl-2,5-bis(dibenzylamino)-6-phenylhexane-3,4-diol
• CAS: 1011256-27-1
• 化学式: C₄₆H₅₄N₂O₂
• 分子量: 666.947
• InChiKey: NBNWUSZEECLVPX-AXYJRABVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.2
• 重原子数：
  50
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  46.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S,4S,5S)-6-cyclohexyl-2,5-bis(dibenzylamino)-1-phenylhexane-3,4-diol 、 二碳酸二叔丁酯 在 palladium dihydroxide 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 96.0h， 以55%的产率得到(2S,3S,4S,5S)-2,5-bis[(tert-butoxycarbonyl)amino]-6-cyclohexylhexane-1-phenylhexane-3,4-diol
  参考文献：
  名称：

  Design, Synthesis, Evaluation, and Crystallographic-Based Structural Studies of HIV-1 Protease Inhibitors with Reduced Response to the V82A Mutation

  摘要：

  In our quest for HIV-1 protease inhibitors that are not affected by the V82A resistance mutation, we have synthesized and tested a second generation set of C-2-symmetric HIV-1 protease inhibitors that contain a cyclohexane group at P1 and/or P1'. The binding affinity results indicate that these compounds have an improved response to the appearance of the V82A mutation than the parent compound. The X-ray structure of one of these compounds with the V82A HIV-1 PR variant provides the structural rationale for the better resistance profile of these compounds. Moreover, scrutiny of the X-ray structure suggests that the ring of the Cha side chain might be in a boat rather than in the chair conformation, a result supported by molecular dynamics simulations.

  DOI：

  10.1021/jm701170f
• 作为产物：
  描述：

  (2S,3S,4S,5S)-1-cyclohexyl-2,5-bis(dibenzylamino)-4-hydroxy-6-phenylhexan-3-yl 2,2,4,4-tetramethyl-1,3-oxazolidine-3-carboxylate 在 甲烷磺酸 、 lithium hydroxide 、 水 作用下， 以 甲醇 、 1,4-二氧六环 为溶剂， 反应 18.0h， 以97%的产率得到(2S,3S,4S,5S)-6-cyclohexyl-2,5-bis(dibenzylamino)-1-phenylhexane-3,4-diol
  参考文献：
  名称：

  Design, Synthesis, Evaluation, and Crystallographic-Based Structural Studies of HIV-1 Protease Inhibitors with Reduced Response to the V82A Mutation

  摘要：

  In our quest for HIV-1 protease inhibitors that are not affected by the V82A resistance mutation, we have synthesized and tested a second generation set of C-2-symmetric HIV-1 protease inhibitors that contain a cyclohexane group at P1 and/or P1'. The binding affinity results indicate that these compounds have an improved response to the appearance of the V82A mutation than the parent compound. The X-ray structure of one of these compounds with the V82A HIV-1 PR variant provides the structural rationale for the better resistance profile of these compounds. Moreover, scrutiny of the X-ray structure suggests that the ring of the Cha side chain might be in a boat rather than in the chair conformation, a result supported by molecular dynamics simulations.

  DOI：

  10.1021/jm701170f

文献信息

• Design, Synthesis, Evaluation, and Crystallographic-Based Structural Studies of HIV-1 Protease Inhibitors with Reduced Response to the V82A Mutation
  作者：José C. Clemente、Arthur Robbins、Paula Graña、M. Rita Paleo、Juan F. Correa、M. Carmen Villaverde、F. Javier Sardina、Lakshmanan Govindasamy、Mavis Agbandje-McKenna、Robert McKenna、Ben M. Dunn、Fredy Sussman

  DOI：10.1021/jm701170f

  日期：2008.2.1

  In our quest for HIV-1 protease inhibitors that are not affected by the V82A resistance mutation, we have synthesized and tested a second generation set of C-2-symmetric HIV-1 protease inhibitors that contain a cyclohexane group at P1 and/or P1'. The binding affinity results indicate that these compounds have an improved response to the appearance of the V82A mutation than the parent compound. The X-ray structure of one of these compounds with the V82A HIV-1 PR variant provides the structural rationale for the better resistance profile of these compounds. Moreover, scrutiny of the X-ray structure suggests that the ring of the Cha side chain might be in a boat rather than in the chair conformation, a result supported by molecular dynamics simulations.