(3,4-Methylendioxybenzoyl)malononitril

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (3,4-Methylendioxybenzoyl)malononitril
• 英文别名: 2-(1,3-Benzodioxole-5-carbonyl)propanedinitrile
• 化学式: C₁₁H₆N₂O₃
• 分子量: 214.18
• InChiKey: OSNKGSPNZCIXAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  83.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3,4-Methylendioxybenzoyl)malononitril 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成 5-Amino-3-benzo[1,3]dioxol-5-yl-1-tert-butyl-1H-pyrazole-4-carbonitrile
  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
• 作为产物：
  描述：

  胡椒酸 在 草酰氯 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (3,4-Methylendioxybenzoyl)malononitril
  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

• SOUTHWICK P. L.; DHAWAN B., J. HETEROCYCL. CHEM. <JHTC-AD>, 1975, 12, NO 6, 1199-1205
  作者：SOUTHWICK P. L.、 DHAWAN B.

  DOI：——

  日期：——
• 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.