(2S)-N-[(1S,2S,3S,4S)-5-cyclohexyl-1-(cyclohexylmethyl)-2,3-dihydroxy-4-[[(2S)-3-methyl-2-[[methyl(2-pyridylmethyl)carbamoyl]amino]butanoyl]amino]pentyl]-3-methyl-2-[[methyl(2-pyridylmethyl)carbamoyl]amino]butanamide | 1011256-41-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-N-[(1S,2S,3S,4S)-5-cyclohexyl-1-(cyclohexylmethyl)-2,3-dihydroxy-4-[[(2S)-3-methyl-2-[[methyl(2-pyridylmethyl)carbamoyl]amino]butanoyl]amino]pentyl]-3-methyl-2-[[methyl(2-pyridylmethyl)carbamoyl]amino]butanamide
• 英文别名: (2S)-N-[(2S,3S,4S,5S)-1,6-dicyclohexyl-3,4-dihydroxy-5-[[(2S)-3-methyl-2-[[methyl(pyridin-2-ylmethyl)carbamoyl]amino]butanoyl]amino]hexan-2-yl]-3-methyl-2-[[methyl(pyridin-2-ylmethyl)carbamoyl]amino]butanamide
• CAS: 1011256-41-9
• 化学式: C₄₄H₇₀N₈O₆
• 分子量: 807.09
• InChiKey: GOFBMDJZIXCQGV-UNHORJANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  58
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  189
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2S,3S,4S,5S)-2,5-diamino-1,6-dicyclohexylhexane-3,4-diol bistrifluoroacetate 、 N-<carbonyl>valine p-nitrophenyl ester 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以36%的产率得到(2S)-N-[(1S,2S,3S,4S)-5-cyclohexyl-1-(cyclohexylmethyl)-2,3-dihydroxy-4-[[(2S)-3-methyl-2-[[methyl(2-pyridylmethyl)carbamoyl]amino]butanoyl]amino]pentyl]-3-methyl-2-[[methyl(2-pyridylmethyl)carbamoyl]amino]butanamide
  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.