5-[1-[(2R)-3-amino-2-hydroxypropyl]-5-methylpyrazol-3-yl]-2-chloro-N-[(1-hydroxycycloheptyl)methyl]benzamide;hydrochloride | 1333869-91-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-[1-[(2R)-3-amino-2-hydroxypropyl]-5-methylpyrazol-3-yl]-2-chloro-N-[(1-hydroxycycloheptyl)methyl]benzamide;hydrochloride
• CAS: 1333869-91-2
• 化学式: C₂₂H₃₁ClN₄O₃*ClH
• 分子量: 471.427
• InChiKey: WABOPISTAPYJDC-UNTBIKODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  113
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-[1-(3-amino-2-hydroxy-propyl)-5-methyl-1H-pyrazol-3-yl]-2-chloro-N-(1-hydroxy-cycloheptylmethyl)-benzamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 5-[1-(3-amino-2-hydroxy-propyl)-5-methyl-1H-pyrazol-3-yl]-2-chloro-N-(1-hydroxy-cycloheptylmethyl)-benzamide hydrochloride 、 5-[1-[(2R)-3-amino-2-hydroxypropyl]-5-methylpyrazol-3-yl]-2-chloro-N-[(1-hydroxycycloheptyl)methyl]benzamide;hydrochloride
  参考文献：
  名称：

  Discovery, synthesis and SAR of azinyl- and azolylbenzamides antagonists of the P2X7 receptor

  摘要：

  The discovery, of a series of 2-Cl-5-heteroaryl-benzamide antagonists of the P2X(7) receptor via parallel medicinal chemistry is described. Initial analogs suffered from poor metabolic stability and low Vd(ss). Multi parametric optimization led to identification of pyrazole 39 as a viable lead with excellent potency and oral bioavailability. Further attempts to improve the low Vd(ss) of 39 via introduction of amines led to analogs 40 and 41 which maintained the favorable pharmacology profile of 39 and improved Vd(ss) after iv dosing. But these analogs suffered from poor oral absorption, probably driven by poor permeability. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.117