[3-[4-[3-[4-[3-(Aminomethyl)phenyl]piperidine-1-carbonyl]phenyl]buta-1,3-diynyl]phenyl]-[4-[3-(aminomethyl)phenyl]piperidin-1-yl]methanone | 1374037-19-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [3-[4-[3-[4-[3-(Aminomethyl)phenyl]piperidine-1-carbonyl]phenyl]buta-1,3-diynyl]phenyl]-[4-[3-(aminomethyl)phenyl]piperidin-1-yl]methanone
• CAS: 1374037-19-0
• 化学式: C₄₂H₄₂N₄O₂
• 分子量: 634.821
• InChiKey: IKFRMOBETBLTOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  48
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [3-[4-[3-[4-[3-(Aminomethyl)phenyl]piperidine-1-carbonyl]phenyl]buta-1,3-diynyl]phenyl]-[4-[3-(aminomethyl)phenyl]piperidin-1-yl]methanone 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 以100%的产率得到[3-[4-[3-[4-[3-(Aminomethyl)phenyl]piperidine-1-carbonyl]phenyl]butyl]phenyl]-[4-[3-(aminomethyl)phenyl]piperidin-1-yl]methanone
  参考文献：
  名称：

  Dimerization of β-tryptase inhibitors, does it work for both basic and neutral P1 groups?

  摘要：

  The tetrameric folding of beta-tryptase and the pair-wise distribution of its substrate binding sites offer a unique opportunity for development of inhibitors that span two adjacent binding sites. A series of dimeric inhibitors with two basic P1 moieties was discovered using this design strategy and exhibited tight-binder characteristics. Using the same strategy, an attempt was made to design and synthesize dimeric inhibitors with two neutral-P1 groups in hope to exploit the dimeric binding mode to achieve a starting point for further optimization. The unsuccessful attempt, however, demonstrated the important role played by Ala190 in neutral-P1 binding and casted further doubt on the possibility of developing neutral-P1 inhibitors for beta-tryptase. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.021
• 作为产物：
  描述：

  3-乙炔基苯甲酸 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 [3-[4-[3-[4-[3-(Aminomethyl)phenyl]piperidine-1-carbonyl]phenyl]buta-1,3-diynyl]phenyl]-[4-[3-(aminomethyl)phenyl]piperidin-1-yl]methanone
  参考文献：
  名称：

  Dimerization of β-tryptase inhibitors, does it work for both basic and neutral P1 groups?

  摘要：

  The tetrameric folding of beta-tryptase and the pair-wise distribution of its substrate binding sites offer a unique opportunity for development of inhibitors that span two adjacent binding sites. A series of dimeric inhibitors with two basic P1 moieties was discovered using this design strategy and exhibited tight-binder characteristics. Using the same strategy, an attempt was made to design and synthesize dimeric inhibitors with two neutral-P1 groups in hope to exploit the dimeric binding mode to achieve a starting point for further optimization. The unsuccessful attempt, however, demonstrated the important role played by Ala190 in neutral-P1 binding and casted further doubt on the possibility of developing neutral-P1 inhibitors for beta-tryptase. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.021

文献信息

• Dimerization of β-tryptase inhibitors, does it work for both basic and neutral P1 groups?
  作者：Guyan Liang、Yong Mi Choi-Sledeski、Xin Chen、Yong Gong、Eric W. MacMillan、Joseph Tsay、Keith Sides、Jennifer Cairns、Berndt Kulitzscher、David J. Aldous、Isabelle Morize、Henry W. Pauls

  DOI：10.1016/j.bmcl.2012.01.021

  日期：2012.5

  The tetrameric folding of beta-tryptase and the pair-wise distribution of its substrate binding sites offer a unique opportunity for development of inhibitors that span two adjacent binding sites. A series of dimeric inhibitors with two basic P1 moieties was discovered using this design strategy and exhibited tight-binder characteristics. Using the same strategy, an attempt was made to design and synthesize dimeric inhibitors with two neutral-P1 groups in hope to exploit the dimeric binding mode to achieve a starting point for further optimization. The unsuccessful attempt, however, demonstrated the important role played by Ala190 in neutral-P1 binding and casted further doubt on the possibility of developing neutral-P1 inhibitors for beta-tryptase. (C) 2012 Elsevier Ltd. All rights reserved.