N2-[2-(2-chlorophenyl)ethyl]-N4-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine | 1375082-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N2-[2-(2-chlorophenyl)ethyl]-N4-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
• 英文别名: 2-N-[2-(2-chlorophenyl)ethyl]-4-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
• CAS: 1375082-23-7
• 化学式: C₁₈H₁₉ClN₆
• 分子量: 354.842
• InChiKey: UEQIBRYPDWTFJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  78.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氨基-5-环丙基-1H-吡唑 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 生成 N2-[2-(2-chlorophenyl)ethyl]-N4-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity against Mycobacterium tuberculosis

  摘要：

  A high-throughput screen against PknB, an essential serine-threonine protein kinase present in Mycobacterium tuberculosis (M. tuberculosis), allowed the identification of an aminoquinazoline inhibitor which was used as a starting point for SAR investigations. Although a significant improvement in enzyme affinity was achieved, the aminoquinazolines showed little or no cellular activity against M. tuberculosis. However, switching to an aminopyrimidine core scaffold and the introduction of a basic amine side chain afforded compounds with nanomolar enzyme binding affinity and micromolar minimum inhibitory concentrations against M. tuberculosis. Replacement of the pyrazole head group with pyridine then allowed equipotent compounds with improved selectivity against a human kinase panel to be obtained. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.107

文献信息

• Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity against Mycobacterium tuberculosis
  作者：Timothy M. Chapman、Nathalie Bouloc、Roger S. Buxton、Jasveen Chugh、Kathryn E.A. Lougheed、Simon A. Osborne、Barbara Saxty、Stephen J. Smerdon、Debra L. Taylor、David Whalley

  DOI：10.1016/j.bmcl.2012.02.107

  日期：2012.5

  A high-throughput screen against PknB, an essential serine-threonine protein kinase present in Mycobacterium tuberculosis (M. tuberculosis), allowed the identification of an aminoquinazoline inhibitor which was used as a starting point for SAR investigations. Although a significant improvement in enzyme affinity was achieved, the aminoquinazolines showed little or no cellular activity against M. tuberculosis. However, switching to an aminopyrimidine core scaffold and the introduction of a basic amine side chain afforded compounds with nanomolar enzyme binding affinity and micromolar minimum inhibitory concentrations against M. tuberculosis. Replacement of the pyrazole head group with pyridine then allowed equipotent compounds with improved selectivity against a human kinase panel to be obtained. (C) 2012 Elsevier Ltd. All rights reserved.