4-benzyloxy-3-cyanobenzoyl chloride | 556836-18-1

• 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: 4-benzyloxy-3-cyanobenzoyl chloride
• 英文别名: 3-Cyano-4-phenylmethoxybenzoyl chloride
• CAS: 556836-18-1
• 化学式: C₁₅H₁₀ClNO₂
• 分子量: 271.703
• InChiKey: BKRBCMKVXBEYBL-UHFFFAOYSA-N

物化性质

• 熔点：
  100-102 °C
• 沸点：
  451.7±35.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  50.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-benzyloxy-3-cyanobenzoyl chloride 在 吡啶 、 四(三苯基膦)钯 、 potassium fluoride dihydrate 、 palladium 10% on activated carbon 、 水 、 氢气 、 三乙胺 、 sodium hydroxide 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 80.0 ℃ 、344.75 kPa 条件下， 反应 18.0h， 生成 2-氰基-4-联苯羧酸
  参考文献：
  名称：

  Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5

  摘要：

  Based on SAR in the alkyne class of mGlu5 receptor negative allosteric modulators and a set of amide-based positive allosteric modulators, optimized substitution of the aryl 'b' ring was used to create substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides. Results from an mGlu5 receptor functional assay, using calcium fluorescence, revealed varying efficacies and potencies that provide evidence that subtle changes in compounds within a close structural class can have marked effects on functional activity including switches in modes of efficacy (i.e., negative to positive allosteric modulation). Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.12.110
• 作为产物：
  描述：

  3-氰基-4-氟苯甲酸 在 氯化亚砜 、 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 生成 4-benzyloxy-3-cyanobenzoyl chloride
  参考文献：
  名称：

  Dual Aromatase−Steroid Sulfatase Inhibitors

  摘要：

  By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.

  DOI：

  10.1021/jm061462b

文献信息

• Structure−Activity Relationships Comparing <i>N</i>-(6-Methylpyridin-yl)-Substituted Aryl Amides to 2-Methyl-6-(substituted-arylethynyl)pyridines or 2-Methyl-4-(substituted-arylethynyl)thiazoles as Novel Metabotropic Glutamate Receptor Subtype 5 Antagonists
  作者：Santosh S. Kulkarni、Mu-Fa Zou、Jianjing Cao、Jeffrey R. Deschamps、Alice L. Rodriguez、P. Jeffrey Conn、Amy Hauck Newman

  DOI：10.1021/jm900172f

  日期：2009.6.11

  The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in anxiety, depression, pain, mental retardation, and addiction. The potent and selective noncompetitive mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP, 1) has been a critically important tool used to further elucidate the role of mGluR5 in these CNS disorders. In an effort to provide novel and structurally diverse selective mGluR5 antagonists, we previously described a set of analogues with moderate activity wherein the alkyne bond was replaced with an amide group. In the present report, extended series of both amide and alkyne-based ligands were synthesized. MGluR5 binding and functional data were obtained that identified (1) several novel alkynes with comparable affinities to 1 at mGluR5 (e.g., 10 and 20-23), but (2) most structural variations to the amide template were not well tolerated, although a few potent amides were discovered (e.g., 55 and 56). Several of these novel analogues show drug-like physical properties (e.g., cLogP range = 2-5) that support their use for in vivo investigation into the role of mGluR5 in CNS disorders.
• Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5
  作者：Mu-Fa Zou、Jianjing Cao、Alice L. Rodriguez、P. Jeffrey Conn、Amy Hauck Newman

  DOI：10.1016/j.bmcl.2010.12.110

  日期：2011.5

  Based on SAR in the alkyne class of mGlu5 receptor negative allosteric modulators and a set of amide-based positive allosteric modulators, optimized substitution of the aryl 'b' ring was used to create substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides. Results from an mGlu5 receptor functional assay, using calcium fluorescence, revealed varying efficacies and potencies that provide evidence that subtle changes in compounds within a close structural class can have marked effects on functional activity including switches in modes of efficacy (i.e., negative to positive allosteric modulation). Published by Elsevier Ltd.
• Dual Aromatase−Steroid Sulfatase Inhibitors
  作者：L. W. Lawrence Woo、Christian Bubert、Oliver B. Sutcliffe、Andrew Smith、Surinder K. Chander、Mary F. Mahon、Atul Purohit、Michael J. Reed、Barry V. L. Potter

  DOI：10.1021/jm061462b

  日期：2007.7.1

  By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.