N-(1H-benzimidazol-2-yl)-3-[[(4R,5S,6S,7R)-3-[[3-(1H-benzimidazol-2-ylcarbamoyl)phenyl]methyl]-4,7-dibenzyl-5,6-bis(2-methoxyethoxymethoxy)-2-oxo-1,3-diazepan-1-yl]methyl]benzamide | 1053700-28-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N-(1H-benzimidazol-2-yl)-3-[[(4R,5S,6S,7R)-3-[[3-(1H-benzimidazol-2-ylcarbamoyl)phenyl]methyl]-4,7-dibenzyl-5,6-bis(2-methoxyethoxymethoxy)-2-oxo-1,3-diazepan-1-yl]methyl]benzamide
• CAS: 1053700-28-9
• 化学式: C₅₇H₆₀N₈O₉
• 分子量: 1001.15
• InChiKey: GBPJJJFUIDSIIQ-DSIMHHNMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  74
• 可旋转键数：
  24
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  195
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-(1H-benzimidazol-2-yl)-3-[[(4R,5S,6S,7R)-3-[[3-(1H-benzimidazol-2-ylcarbamoyl)phenyl]methyl]-4,7-dibenzyl-5,6-bis(2-methoxyethoxymethoxy)-2-oxo-1,3-diazepan-1-yl]methyl]benzamide 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 18.0h， 生成 (R-(4α,5α,6β,7β))-3,3'-[(tetrahydro-5,6-dihydroxy-2-oxo-4,7-bis(phenylmethyl)-1H-1,3-diazepine-1,3(2H)-diyl)bis(methylene)]bis[N-1H-benzimidazol-2-ylbenzamide]
  参考文献：
  名称：

  Cyclic Urea Amides:  HIV-1 Protease Inhibitors with Low Nanomolar Potency against both Wild Type and Protease Inhibitor Resistant Mutants of HIV

  摘要：

  Cyclic urea amides, a novel series of HIV-1 protease (HIV PR) inhibitors, have increased activity against drug-resistant mutants of the HIV PR. The design strategy for these inhibitors is based on the hypotheses that (i) the hydrogen-bonding interactions between the inhibitor and the protease backbone will remain constant for wild-type and mutant enzymes and (ii) inhibitors which are capable of forming many nonbonded interactions, distributed throughout the active site, will experience a lower percent change in binding energy as a result of mutation in the target enzyme than those that form fewer interactions by partial occupation of the active site. The cyclic urea amide, SD146, forms 14 hydrogen bonds and 191 van der Waals contacts to HIV PR. SD146 is a very potent antiviral agent (IC90 = 5.1 nM) against wild-type HIV and maintains the same or improved level of high potency against a range of mutant strains of HIV with resistance to a wide variety of HIV protease inhibitors.

  DOI：

  10.1021/jm960586t
• 作为产物：
  描述：

  (4R,5S,6S,7R)-hexahydro-5,6-bis(2-methoxyethoxymethoxy)-4,7-bis(phenylmethyl)-2H-1,3-diazepin-2-one 在 氢氧化钾 、 sodium hydride 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 N-(1H-benzimidazol-2-yl)-3-[[(4R,5S,6S,7R)-3-[[3-(1H-benzimidazol-2-ylcarbamoyl)phenyl]methyl]-4,7-dibenzyl-5,6-bis(2-methoxyethoxymethoxy)-2-oxo-1,3-diazepan-1-yl]methyl]benzamide
  参考文献：
  名称：

  Cyclic Urea Amides:  HIV-1 Protease Inhibitors with Low Nanomolar Potency against both Wild Type and Protease Inhibitor Resistant Mutants of HIV

  摘要：

  Cyclic urea amides, a novel series of HIV-1 protease (HIV PR) inhibitors, have increased activity against drug-resistant mutants of the HIV PR. The design strategy for these inhibitors is based on the hypotheses that (i) the hydrogen-bonding interactions between the inhibitor and the protease backbone will remain constant for wild-type and mutant enzymes and (ii) inhibitors which are capable of forming many nonbonded interactions, distributed throughout the active site, will experience a lower percent change in binding energy as a result of mutation in the target enzyme than those that form fewer interactions by partial occupation of the active site. The cyclic urea amide, SD146, forms 14 hydrogen bonds and 191 van der Waals contacts to HIV PR. SD146 is a very potent antiviral agent (IC90 = 5.1 nM) against wild-type HIV and maintains the same or improved level of high potency against a range of mutant strains of HIV with resistance to a wide variety of HIV protease inhibitors.

  DOI：

  10.1021/jm960586t

文献信息

• Cyclic Urea Amides:  HIV-1 Protease Inhibitors with Low Nanomolar Potency against both Wild Type and Protease Inhibitor Resistant Mutants of HIV
  作者：Prabhakar K. Jadhav、Paul Ala、Francis J. Woerner、Chong-Hwan Chang、Sena S. Garber、Elizabeth D. Anton、Lee T. Bacheler

  DOI：10.1021/jm960586t

  日期：1997.1.1

  Cyclic urea amides, a novel series of HIV-1 protease (HIV PR) inhibitors, have increased activity against drug-resistant mutants of the HIV PR. The design strategy for these inhibitors is based on the hypotheses that (i) the hydrogen-bonding interactions between the inhibitor and the protease backbone will remain constant for wild-type and mutant enzymes and (ii) inhibitors which are capable of forming many nonbonded interactions, distributed throughout the active site, will experience a lower percent change in binding energy as a result of mutation in the target enzyme than those that form fewer interactions by partial occupation of the active site. The cyclic urea amide, SD146, forms 14 hydrogen bonds and 191 van der Waals contacts to HIV PR. SD146 is a very potent antiviral agent (IC90 = 5.1 nM) against wild-type HIV and maintains the same or improved level of high potency against a range of mutant strains of HIV with resistance to a wide variety of HIV protease inhibitors.