2-[(2S,6S)-6-benzyl-2-[3-(diaminomethylideneamino)propyl]-3,8,14-trioxo-1,4,7-triazacyclotetradec-4-yl]acetamide | 1245141-42-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 2-[(2S,6S)-6-benzyl-2-[3-(diaminomethylideneamino)propyl]-3,8,14-trioxo-1,4,7-triazacyclotetradec-4-yl]acetamide
• CAS: 1245141-42-7
• 化学式: C₂₄H₃₇N₇O₄
• 分子量: 487.602
• InChiKey: DHNWGZWKCRADTR-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  186
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  庚二酸 、 Fmoc-甘氨酸 、 allyl (S)-(1-oxo-3-phenylpropan-2-yl)carbamate 、 Fmoc-Pbf-L-精氨酸 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以2.1%的产率得到2-[(2S,6S)-6-benzyl-2-[3-(diaminomethylideneamino)propyl]-3,8,14-trioxo-1,4,7-triazacyclotetradec-4-yl]acetamide
  参考文献：
  名称：

  Rational conversion of noncontinuous active region in proteins into a small orally bioavailable macrocyclic drug-like molecule: The HIV-1 CD4:gp120 paradigm

  摘要：

  Rational conversion of noncontinuous active regions of proteins into a small orally bioavailable molecule is crucial for the discovery of new drugs based on inhibition of protein-protein interactions. We developed a method that utilizes backbone cyclization as an intermediate step for conversion of the CD4 noncontinuous active region into small macrocyclic molecules. We demonstrate that this method is feasible by preparing small inhibitor for human immunodeficiency virus infection. The lead compound, CG-1, proved orally available in the rat model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.053

文献信息

• Rational conversion of noncontinuous active region in proteins into a small orally bioavailable macrocyclic drug-like molecule: The HIV-1 CD4:gp120 paradigm
  作者：Mattan Hurevich、Avi Swed、Salim Joubran、Shira Cohen、Noam S. Freeman、Elena Britan-Rosich、Laurence Briant-Longuet、Martine Bardy、Christian Devaux、Moshe Kotler、Amnon Hoffman、Chaim Gilon

  DOI：10.1016/j.bmc.2010.04.053

  日期：2010.8

  Rational conversion of noncontinuous active regions of proteins into a small orally bioavailable molecule is crucial for the discovery of new drugs based on inhibition of protein-protein interactions. We developed a method that utilizes backbone cyclization as an intermediate step for conversion of the CD4 noncontinuous active region into small macrocyclic molecules. We demonstrate that this method is feasible by preparing small inhibitor for human immunodeficiency virus infection. The lead compound, CG-1, proved orally available in the rat model. (C) 2010 Elsevier Ltd. All rights reserved.