(R,S)-α-cyano-3-phenoxyphenylacetonitrile | 897445-61-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R,S)-α-cyano-3-phenoxyphenylacetonitrile
• 英文别名: α-cyano-3-phenoxyphenylacetonitrile；2-(3-Phenoxyphenyl)propanedinitrile
• CAS: 897445-61-3
• 化学式: C₁₅H₁₀N₂O
• 分子量: 234.257
• InChiKey: GDAGSFYVJCPBEQ-UHFFFAOYSA-N

物化性质

• 沸点：
  384.5±32.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  56.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  硫酸二甲酯 、 (R,S)-α-cyano-3-phenoxyphenylacetonitrile 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 生成 2-(Methoxy(3-phenoxyphenyl)methylene)malononitrile
  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：

  3-苯氧基苯甲酸 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 (R,S)-α-cyano-3-phenoxyphenylacetonitrile
  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

• Preparation of mixtures of cypermethrin or cyfluthrin isomers enriched
  申请人：FMC Corporation

  公开号：US05028731A1

  公开（公告）日：1991-07-02

  A mixture of isomers of cypermethrin or cyfluthrin enriched in the more insecticidally active c.sub.2 or t.sub.2 isomer, or both, is prepared by adding .alpha.-hydroxy-3-phenoxyphenylacetonitrile or its 4-fluoro analog to a refluxing solution of 3-(2,2-dichloroethenyl)-2-2-dimethylcyclopropanecarbonyl chloride in a hydrocarbon solvent boiling in the range of about 75.degree. to 115.degree. C. in an inert atmosphers, without an acid acceptor being present in the reaction mixture. The product is recovered by washing the reaction mixture with aqueous base.

  将氯氰菊酯或氟氰菊酯的异构体混合物富集在更具杀虫活性的c.sub.2或t.sub.2异构体中，或两者兼有，通过将α-羟基-3-苯氧基苯乙腈或其4-氟代物加入至3-(2,2-二氯乙烯基)-2-2-二甲基环丙烷羧酰氯的回流溶液中，在沸点约为75°C至115°C的烃溶剂中，在惰性气氛下进行反应，反应混合物中不含酸受体。通过用碱性水洗涤反应混合物来回收产物。
• Beyond U0126. Dianion chemistry leading to the rapid synthesis of a series of potent MEK inhibitors
  作者：John Wityak、Frank W. Hobbs、Daniel S. Gardner、Joseph B. Santella、Joseph J. Petraitis、Jung-Hui Sun、Margaret F. Favata、Andrea J. Daulerio、Kurumi Y. Horiuchi、Robert A. Copeland、Peggy A. Scherle、Bruce D. Jaffe、James M. Trzaskos、Ronald L. Magolda、George L. Trainor、John V. Duncia

  DOI：10.1016/j.bmcl.2004.01.012

  日期：2004.3

  Employing phenylmalonitrile dianion chemistry, a large number of analogues of MEK inhibitor lead SH053 (IC50 = 140 nM) were rapidly synthesized leading to single digit nM inhibitors, displaying submicromolar AP-1 transcription inhibition in COS-7 cells. Compound 41, exhibiting a MEK IC50 = 12 nM showed ip activity in a TPA-induced car edema model with an ED50 = 5 mg/kg. (C) 2004 Elsevier Ltd. All rights reserved.
• PREPARATION OF MIXTURES OF CYPERMETHRIN OR CYFLUTHRIN ISOMERS ENRICHED IN MORE ACTIVE SPECIES
  申请人：FMC CORPORATION

  公开号：EP0500572A1

  公开（公告）日：1992-09-02
• EP0500572A4
  申请人：——

  公开号：EP0500572A4

  公开（公告）日：1992-10-07
• US5028731A
  申请人：——

  公开号：US5028731A

  公开（公告）日：1991-07-02