1-Tert-butyl-3-[(3-chloro-2-fluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine | 956026-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 1-Tert-butyl-3-[(3-chloro-2-fluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 956026-08-7
• 化学式: C₁₆H₁₇ClFN₅
• 分子量: 333.796
• InChiKey: GBHGMHXJCONSRT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氯-2-氟苯乙酸 在 草酰氯 、 sodium hydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 1-Tert-butyl-3-[(3-chloro-2-fluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii

  摘要：

  Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.

  DOI：

  10.1021/jm4001314

文献信息

• MODULATION OF PROTEIN TRAFFICKING
  申请人：Bulawa Christine Ellen

  公开号：US20100331297A1

  公开（公告）日：2010-12-30

  Compounds and compositions are provided for treatment or amelioration of one or more disorders characterized by defects in protein trafficking. A method of treating a disorder characterized by impaired protein trafficking includes administering to a subject or contacting a cell with a compound of Formula I: [formula here] or pharmaceutically acceptable salts or derivatives thereof.

  本发明提供用于治疗或改善由蛋白质运输缺陷所特征的一个或多个疾病的化合物和组合物。一种治疗由蛋白质运输受损所特征的疾病的方法包括向受试者施用或与细胞接触化合物I的药物或其药学上可接受的盐或衍生物。[公式在此]
• Optimizing Small Molecule Inhibitors of Calcium-Dependent Protein Kinase 1 to Prevent Infection by Toxoplasma gondii
  作者：Sebastian Lourido、Chao Zhang、Michael S. Lopez、Keliang Tang、Jennifer Barks、Qiuling Wang、Scott A. Wildman、Kevan M. Shokat、L. David Sibley

  DOI：10.1021/jm4001314

  日期：2013.4.11

  Toxoplasma gondii is sensitive to bulky pyrazolo [3,4-d] pyrimidine (PP) inhibitors due to the presence of a Gly gatekeeper in the essential calcium dependent protein kinase 1 (CDPK1). Here we synthesized a number of new derivatives of 3-methyl-benzyl-PP (3-MB-PP, or 1). The potency of PP analogues in inhibiting CDPK1 enzyme activity in vitro (low nM IC50 values) and blocking parasite growth in host cell monolayers in vivo (low mu M EC50 values) were highly correlated and occurred in a CDPK1-specific manner. Chemical modification of the PP scaffold to increase half-life in the presence of microsomes in vitro led to identification of compounds with enhanced stability while retaining activity. Several of these more potent compounds were able to prevent lethal infection with T. gondii in the mouse model. Collectively, the strategies outlined here provide a route for development of more effective compounds for treatment of toxoplasmosis and perhaps related parasitic diseases.