(S)-2-[(Adamantane-1-carbonyl)-amino]-4-methyl-pentanoic acid methyl ester | 561327-50-2

• 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: (S)-2-[(Adamantane-1-carbonyl)-amino]-4-methyl-pentanoic acid methyl ester
• 英文别名: N-(Tricyclo[3.3.1.13,7]dec-1-ylcarbonyl)-L-leucine methyl ester；methyl (2S)-2-(adamantane-1-carbonylamino)-4-methylpentanoate
• CAS: 561327-50-2
• 化学式: C₁₈H₂₉NO₃
• 分子量: 307.433
• InChiKey: IXNFXTCKUSNASR-URZJAHPPSA-N

物化性质

• 熔点：
  137-138 °C
• 沸点：
  439.0±14.0 °C(Predicted)
• 密度：
  1.107±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-[(Adamantane-1-carbonyl)-amino]-4-methyl-pentanoic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以87%的产率得到(S)-2-[(Adamantane-1-carbonyl)-amino]-4-methyl-pentanoic acid
  参考文献：
  名称：

  Synthesis of 1-Boraadamantaneamine Derivatives with Selective Astrocyte vs C6 Glioma Antiproliferative Activity. A Novel Class of Anti-Hepatitis C Agents with Potential to Bind CD81

  摘要：

  A variety of amine complexes with 1-boraadamatane were synthesized and subsequently evaluated for an antiproliferative effect on CD81-enriched cell lines to provide evidence for binding and activation of CD81. CD81 is a member of the tetraspanin family of membrane proteins found in all cell lineages in the liver. CD81 signals for antiproliferation when bound by antibodies. It is known that the HCV-E2 envelope glycoprotein binds to the CD81 protein. While it is unclear whether virus entry into host cells is directly linked to virus attachment via CD81 for HCV, this step in the viral life cycle has recently proven to be an effective point of attack for other viruses including HIV and rhinoviruses. The aim of the current study concerns the synthesis of amantidine analogues by appending primary amines to 1-boraadamantane to evaluate such compounds for CD81-dependent antiproliferation of CD81-enriched cell lines (astrocyte) vs CD81-deficient cell lines (C6 glioma). If the antiproliferative effect of these amantidine analogues proves to be an effect of binding and activating CD81, then these compounds may have the potential to prevent or treat HCV infections. Each compound's potential for preventive and therapeutic activity stems from the compound's potential to block viral attachment, virus-cell fusion, or virus entry into host cells or to counter potential mechanisms of HCV immune evasion. Out of a library of over 500 compounds, including randomly selected small molecules and rationally designed small molecules, only the 1-boraadamantaneamine compounds and structurally similar analogues display a significant antiproliferative effect on the CD81-enriched astrocytes relative to the CD81-deficient cell lines. In fact, 1-boraadamantane.L-phenylalanine methyl ester complex (5), 1-boraadamantane.ethanolamine complex (8), and (S)-2-[(adamantane-1-carbonyl)amino]-3-phenylpropionic acid (15) show a dose-dependent, astrocyte-selective antiproliferative activity in the concentration range 0.1-10 muM. This is consistent with the binding and activation of CD81 and represents a 2-fold improvement compared to the clinically prescribed anti-HCV agent, amantidine, in the same concentration range. Consequently, the 1-boraadamantaneamine derivatives present a promising lead in the development of small molecules with potential to bind to CD81 and treat HCV infections.

  DOI：

  10.1021/jm020326d
• 作为产物：
  描述：

  1-金刚烷甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 苯 为溶剂， 反应 1.0h， 生成 (S)-2-[(Adamantane-1-carbonyl)-amino]-4-methyl-pentanoic acid methyl ester
  参考文献：
  名称：

  Synthesis of 1-Boraadamantaneamine Derivatives with Selective Astrocyte vs C6 Glioma Antiproliferative Activity. A Novel Class of Anti-Hepatitis C Agents with Potential to Bind CD81

  摘要：

  A variety of amine complexes with 1-boraadamatane were synthesized and subsequently evaluated for an antiproliferative effect on CD81-enriched cell lines to provide evidence for binding and activation of CD81. CD81 is a member of the tetraspanin family of membrane proteins found in all cell lineages in the liver. CD81 signals for antiproliferation when bound by antibodies. It is known that the HCV-E2 envelope glycoprotein binds to the CD81 protein. While it is unclear whether virus entry into host cells is directly linked to virus attachment via CD81 for HCV, this step in the viral life cycle has recently proven to be an effective point of attack for other viruses including HIV and rhinoviruses. The aim of the current study concerns the synthesis of amantidine analogues by appending primary amines to 1-boraadamantane to evaluate such compounds for CD81-dependent antiproliferation of CD81-enriched cell lines (astrocyte) vs CD81-deficient cell lines (C6 glioma). If the antiproliferative effect of these amantidine analogues proves to be an effect of binding and activating CD81, then these compounds may have the potential to prevent or treat HCV infections. Each compound's potential for preventive and therapeutic activity stems from the compound's potential to block viral attachment, virus-cell fusion, or virus entry into host cells or to counter potential mechanisms of HCV immune evasion. Out of a library of over 500 compounds, including randomly selected small molecules and rationally designed small molecules, only the 1-boraadamantaneamine compounds and structurally similar analogues display a significant antiproliferative effect on the CD81-enriched astrocytes relative to the CD81-deficient cell lines. In fact, 1-boraadamantane.L-phenylalanine methyl ester complex (5), 1-boraadamantane.ethanolamine complex (8), and (S)-2-[(adamantane-1-carbonyl)amino]-3-phenylpropionic acid (15) show a dose-dependent, astrocyte-selective antiproliferative activity in the concentration range 0.1-10 muM. This is consistent with the binding and activation of CD81 and represents a 2-fold improvement compared to the clinically prescribed anti-HCV agent, amantidine, in the same concentration range. Consequently, the 1-boraadamantaneamine derivatives present a promising lead in the development of small molecules with potential to bind to CD81 and treat HCV infections.

  DOI：

  10.1021/jm020326d

文献信息

• Synthesis of 1-Boraadamantaneamine Derivatives with Selective Astrocyte vs C6 Glioma Antiproliferative Activity. A Novel Class of Anti-Hepatitis C Agents with Potential to Bind CD81
  作者：Carl E. Wagner、Michael L. Mohler、Gyong Suk Kang、Duane D. Miller、Eldon E. Geisert、Yu-An Chang、Everly B. Fleischer、Kenneth J. Shea

  DOI：10.1021/jm020326d

  日期：2003.7.1

  A variety of amine complexes with 1-boraadamatane were synthesized and subsequently evaluated for an antiproliferative effect on CD81-enriched cell lines to provide evidence for binding and activation of CD81. CD81 is a member of the tetraspanin family of membrane proteins found in all cell lineages in the liver. CD81 signals for antiproliferation when bound by antibodies. It is known that the HCV-E2 envelope glycoprotein binds to the CD81 protein. While it is unclear whether virus entry into host cells is directly linked to virus attachment via CD81 for HCV, this step in the viral life cycle has recently proven to be an effective point of attack for other viruses including HIV and rhinoviruses. The aim of the current study concerns the synthesis of amantidine analogues by appending primary amines to 1-boraadamantane to evaluate such compounds for CD81-dependent antiproliferation of CD81-enriched cell lines (astrocyte) vs CD81-deficient cell lines (C6 glioma). If the antiproliferative effect of these amantidine analogues proves to be an effect of binding and activating CD81, then these compounds may have the potential to prevent or treat HCV infections. Each compound's potential for preventive and therapeutic activity stems from the compound's potential to block viral attachment, virus-cell fusion, or virus entry into host cells or to counter potential mechanisms of HCV immune evasion. Out of a library of over 500 compounds, including randomly selected small molecules and rationally designed small molecules, only the 1-boraadamantaneamine compounds and structurally similar analogues display a significant antiproliferative effect on the CD81-enriched astrocytes relative to the CD81-deficient cell lines. In fact, 1-boraadamantane.L-phenylalanine methyl ester complex (5), 1-boraadamantane.ethanolamine complex (8), and (S)-2-[(adamantane-1-carbonyl)amino]-3-phenylpropionic acid (15) show a dose-dependent, astrocyte-selective antiproliferative activity in the concentration range 0.1-10 muM. This is consistent with the binding and activation of CD81 and represents a 2-fold improvement compared to the clinically prescribed anti-HCV agent, amantidine, in the same concentration range. Consequently, the 1-boraadamantaneamine derivatives present a promising lead in the development of small molecules with potential to bind to CD81 and treat HCV infections.