| 545380-40-3

• 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
• CAS: 545380-40-3
• 化学式: C₃₆H₄₂N₂O₅
• 分子量: 582.74
• InChiKey: FXQYJSACAXDRTO-OLUZHXLYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.36
• 重原子数：
  43.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  76.15
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 sodium hydroxide 、 WSC*HCl 、 1-羟基苯并三唑 作用下， 以 甲醇 、 氯仿 为溶剂， 生成
  参考文献：
  名称：

  Identification of a Novel 4-Aminomethylpiperidine Class of M₃ Muscarinic Receptor Antagonists and Structural Insight into Their M₃ Selectivity

  摘要：

  Identification of a novel class of potent and highly selective M-3 muscarinic antagonists is described. First, the structure-activity relationship in the cationic amine core of our previously reported triphenylpropionamide class of M-3 selective antagonists was explored by a small diamine library constructed in solid phase. This led to the identification of M-3 antagonists with a novel piperidine pharmacophore and significantly improved subtype selectivity from a previously reported class. Successive modification on the terminal triphenylpropionamide part of the newly identified class gave 14a as a potent M-3 selective antagonist that had > 100-fold selectivity versus the M-1, M-2, M-4, and M-5 receptors (M-3: K-i = 0.30 nM, M-1/M-3 = 570-fold, M-2/M-3 = 1600-fold, M-4/M-3 = 140-fold, M-5/M-3 = 12000-fold). The possible rationale for its extraordinarily higher subtype selectivity than reported M-3 antagonists was hypothesized by sequence alignment of multiple muscarinic receptors and a computational docking of 14a into transmembrane domains of M-3 receptors.

  DOI：

  10.1021/jm051205r
• 作为产物：
  描述：

  (4R)-(叔丁氧基)-1-(苯甲氧羰基)-L-脯氨酸 在 palladium dihydroxide 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 氯仿 为溶剂， 生成
  参考文献：
  名称：

  Identification of novel muscarinic M3 selective antagonists with a conformationally restricted Hyp-Pro spacer

  摘要：

  The identification of potent and selective muscarinic M-3 antagonists that are based on the recently discovered triphenylpropioamide derivative, 1, and have a unique amino acid spacer group is described. The introduction of a hydroxyproline-proline group to the spacer site and the use of a propyl or cyclopropylmethyl group as the piperidine N-substituent led to the discovery of the novel M-3 selective antagonists [8c, 8g; K-i < 2 nM (M-3), M-1/M-3 > 700-fold, M-2/M-3 > 180-fold], which have a more rigid structure than 1. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00843-0