1-{4-[6-amino-5-(4-chlorophenyl)pyridin-3-yl]phenyl}cyclopentanecarboxylic acid | 2007910-37-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-{4-[6-amino-5-(4-chlorophenyl)pyridin-3-yl]phenyl}cyclopentanecarboxylic acid
• 英文别名: 1-{4-[6-Amino-5-(4-Chlorophenyl)pyridin-3-Yl]phenyl}cyclopentane-1-Carboxylic Acid；1-[4-[6-amino-5-(4-chlorophenyl)pyridin-3-yl]phenyl]cyclopentane-1-carboxylic acid
• CAS: 2007910-37-2
• 化学式: C₂₃H₂₁ClN₂O₂
• 分子量: 392.885
• InChiKey: VHQILBJBMFWZGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-溴苯基)环戊烷甲腈 在 四(三苯基膦)钯 、 硫酸 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 24.0h， 生成 1-{4-[6-amino-5-(4-chlorophenyl)pyridin-3-yl]phenyl}cyclopentanecarboxylic acid
  参考文献：
  名称：

  2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety

  摘要：

  Studies have linked the serine-threonine kinase MAP4K4 to the regulation of a number of biological processes and/or diseases, including diabetes, cancer, inflammation, and angiogenesis. With a majority of the members of our lead series (e.g., 1) suffering from time-dependent inhibition (TDI) of CYP3A4, we sought design avenues that would eliminate this risk. One such approach arose from the observation that carboxylic acid-based intermediates employed in our discovery efforts retained high MAP4K4 inhibitory potency and were devoid of the TDI risk. The medicinal chemistry effort that led to the discovery of this central nervous system-impaired inhibitor together with its preclinical safety profile is described.

  DOI：

  10.1021/acs.jmedchem.8b00152

文献信息

• 2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety
  作者：Robert L. Dow、Mark Ammirati、Scott W. Bagley、Samit K. Bhattacharya、Leonard Buckbinder、Christian Cortes、Ayman F. El-Kattan、Kristen Ford、Gary B. Freeman、Cristiano R. W. Guimarães、Shenping Liu、Mark Niosi、Athanasia Skoura、David Tess

  DOI：10.1021/acs.jmedchem.8b00152

  日期：2018.4.12

  Studies have linked the serine-threonine kinase MAP4K4 to the regulation of a number of biological processes and/or diseases, including diabetes, cancer, inflammation, and angiogenesis. With a majority of the members of our lead series (e.g., 1) suffering from time-dependent inhibition (TDI) of CYP3A4, we sought design avenues that would eliminate this risk. One such approach arose from the observation that carboxylic acid-based intermediates employed in our discovery efforts retained high MAP4K4 inhibitory potency and were devoid of the TDI risk. The medicinal chemistry effort that led to the discovery of this central nervous system-impaired inhibitor together with its preclinical safety profile is described.