benzyl (2S)-2-[2-[(3S)-3-[[(1R)-2-hydroxy-1-phenylethyl]amino]-4-methoxy-4-oxobutyl]-N-methyl-3-octylanilino]-3-methylbutanoate | 887906-32-3

• 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: benzyl (2S)-2-[2-[(3S)-3-[[(1R)-2-hydroxy-1-phenylethyl]amino]-4-methoxy-4-oxobutyl]-N-methyl-3-octylanilino]-3-methylbutanoate
• CAS: 887906-32-3
• 化学式: C₄₀H₅₆N₂O₅
• 分子量: 644.895
• InChiKey: FEQXNZWFZFJJFA-LYDQXETESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.9
• 重原子数：
  47
• 可旋转键数：
  23
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzyl (2S)-2-[2-[(3S)-3-[[(1R)-2-hydroxy-1-phenylethyl]amino]-4-methoxy-4-oxobutyl]-N-methyl-3-octylanilino]-3-methylbutanoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.32 kPa 条件下， 反应 18.0h， 生成
  参考文献：
  名称：

  Design and Synthesis of 8-Octyl-benzolactam-V9, a Selective Activator for Protein Kinase Cε and η

  摘要：

  Conventional (alpha, beta I, beta II, gamma) and novel (delta, epsilon, eta, theta) protein kinase C (PKC) isozymes are main targets of tumor promoters, such as phorbol esters and indolactam-V ( ILV). We have recently found that 1-hexyl derivatives of indolinelactam-V ( 2, 3), in which the indole ring of ILV was replaced with the indoline ring, showed a binding preference for novel PKCs over conventional PKCs. To develop a new ILV analogue displaying increased synthetic accessibility and improved binding selectivity for novel PKCs, we have designed 8-octyl-benzolactam-V9 ( 4), a simple analogue without the pyrrolidine moiety of 2 and 3. Compound 4 showed significant binding selectivity for isolated C1B domains of novel PKCs. Moreover, 4 translocated PKC epsilon and eta from the cytoplasm to the plasma membrane of HeLa cells at 1 mu M, whereas other PKC isozymes did not respond even at 10 mu M. These results indicate that 4 could be a selective activator for PKC epsilon and eta.

  DOI：

  10.1021/jm050857c
• 作为产物：
  描述：

  2-溴-6-硝基苄溴 在 palladium on activated charcoal 吡啶 、 2,6-二甲基吡啶 、 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium hydroxide 、 copper(l) iodide 、 锂硼氢 、 氯化亚砜 、 硼烷 、 氢气 、 sodium hydride 、 戴斯-马丁氧化剂 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 120.0 ℃ 、101.33 kPa 条件下， 反应 109.67h， 生成 benzyl (2S)-2-[2-[(3S)-3-[[(1R)-2-hydroxy-1-phenylethyl]amino]-4-methoxy-4-oxobutyl]-N-methyl-3-octylanilino]-3-methylbutanoate
  参考文献：
  名称：

  Design and Synthesis of 8-Octyl-benzolactam-V9, a Selective Activator for Protein Kinase Cε and η

  摘要：

  Conventional (alpha, beta I, beta II, gamma) and novel (delta, epsilon, eta, theta) protein kinase C (PKC) isozymes are main targets of tumor promoters, such as phorbol esters and indolactam-V ( ILV). We have recently found that 1-hexyl derivatives of indolinelactam-V ( 2, 3), in which the indole ring of ILV was replaced with the indoline ring, showed a binding preference for novel PKCs over conventional PKCs. To develop a new ILV analogue displaying increased synthetic accessibility and improved binding selectivity for novel PKCs, we have designed 8-octyl-benzolactam-V9 ( 4), a simple analogue without the pyrrolidine moiety of 2 and 3. Compound 4 showed significant binding selectivity for isolated C1B domains of novel PKCs. Moreover, 4 translocated PKC epsilon and eta from the cytoplasm to the plasma membrane of HeLa cells at 1 mu M, whereas other PKC isozymes did not respond even at 10 mu M. These results indicate that 4 could be a selective activator for PKC epsilon and eta.

  DOI：

  10.1021/jm050857c

文献信息

• Design and Synthesis of 8-Octyl-benzolactam-V9, a Selective Activator for Protein Kinase Cε and η
  作者：Yu Nakagawa、Kazuhiro Irie、Ryo C. Yanagita、Hajime Ohigashi、Ken-ichiro Tsuda、Kaori Kashiwagi、Naoaki Saito

  DOI：10.1021/jm050857c

  日期：2006.5.1

  Conventional (alpha, beta I, beta II, gamma) and novel (delta, epsilon, eta, theta) protein kinase C (PKC) isozymes are main targets of tumor promoters, such as phorbol esters and indolactam-V ( ILV). We have recently found that 1-hexyl derivatives of indolinelactam-V ( 2, 3), in which the indole ring of ILV was replaced with the indoline ring, showed a binding preference for novel PKCs over conventional PKCs. To develop a new ILV analogue displaying increased synthetic accessibility and improved binding selectivity for novel PKCs, we have designed 8-octyl-benzolactam-V9 ( 4), a simple analogue without the pyrrolidine moiety of 2 and 3. Compound 4 showed significant binding selectivity for isolated C1B domains of novel PKCs. Moreover, 4 translocated PKC epsilon and eta from the cytoplasm to the plasma membrane of HeLa cells at 1 mu M, whereas other PKC isozymes did not respond even at 10 mu M. These results indicate that 4 could be a selective activator for PKC epsilon and eta.