4-Ethoxy-3-hydroxybenzonitrile | 203575-69-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-Ethoxy-3-hydroxybenzonitrile
• CAS: 203575-69-3
• 化学式: C₉H₉NO₂
• 分子量: 163.176
• InChiKey: VSCNGPUYCUMFLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Ethoxy-3-hydroxybenzonitrile 在 吡啶 、 diammonium sulfide 、 caesium carbonate 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Development of New Deoxycytidine Kinase Inhibitors and Noninvasive in Vivo Evaluation Using Positron Emission Tomography

  摘要：

  Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest, and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure activity relationship study was carried out Positron Emission Tomography (PET) using F-18-L-1-(2'-deoxy-2':-FluoroArabinofuranosyl) Cytosine (F-18-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC50 = similar to 1-12 nM) using the F-18-L-FAC PET pharmacodynatnic assay identified compounds demonstrating superior in vivo efficacy.

  DOI：

  10.1021/jm400457y

文献信息

• NOVEL BENZOFURAN-4-CARBOXAMIDES
  申请人：Byk Gulden Lomberg Chemische Fabrik GmbH

  公开号：EP0923568A1

  公开（公告）日：1999-06-23
• US6211203B1
  申请人：——

  公开号：US6211203B1

  公开（公告）日：2001-04-03
• [EN] NOVEL BENZOFURAN-4-CARBOXAMIDES<br/>[FR] NOUVEAUX BENZOFURAN-4-CARBOXAMIDES
  申请人：——

  公开号：WO1998007715A1

  公开（公告）日：1998-02-26

  [EN] Compounds of formula (I) in which R1 is 1-2C-alkoxy or 1-2C-alkoxy which is completely or mainly substituted by fluorine, R2 is 1-7C-alkyl, 3-7C-cycloalkyl or 3-7C-cycloalkylmethyl, Ar is phenyl, pyridyl, phenyl which is substituted by R3, R4 and R5 or pyridyl which is substituted by R6, R7, R8 and R9, where R3 is hydroxyl, halogen, cyano, carboxyl, trifluoromethyl, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl, 1-4C-alkylcarbonyl, 1-4C-alkylcarbonyloxy, amino, mono- or di-1-4C-alkylamino or 1-4C-alkylcarbonylamino, R4 is hydrogen, hydroxyl, halogen, amino, trifluoromethyl, 1-4C-alkyl or 1-4C-alkoxy, R5 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy, R6 is hydroxyl, halogen, cyano, carboxyl, 1-4C-alkyl, 1-4C-alkoxy, 1-4C-alkoxycarbonyl or amino, R7 is hydrogen, halogen, amino or 1-4C-alkyl, R8 is hydrogen or halogen and R9 is hydrogen or halogen, the salts of this compound, and the N-oxides of the pyridines and their salts are active bronchial therapeutics.
  [FR] Les composés de la formule (I) où R1 est 1-2C-alkoxy ou 1-2C-alkoxy, qui est entièrement or principalement substitué par la fluorine, R2 est 1-7C-alkyle, 3-7C-cycloalkyle ou 3-7C-cycloalkylméthyle, Ar est phényle, pyridyle, phényle qui est substitué R3, R4 et R5 ou pyridyle qui est substitué par R6, R7, R8 et R9, où est R3 est hydroxyle, halogène, cyano, carboxyle, trifluorométhyle, 1-4C-alkyle, 1-4C-alkoxy, 1-4C-alkoxycarbonyle, 1-4C-alkylcarbonyle, 1-4C-Alkylcarbonyloxy, amino, mono- or di-1-4C-alkylamino ou 1-4C-alkylcarbonylamino, R4 est hydrogène, hydroxyle, halogène, amino, trifluorométhyle, 1-4C-alkyle ou 1-4C-alkoxy, R5 is hydrogène, halogène, 1-4C-alkyle or 1-4C-alkoxy, R6 is hydroxyle, halogène, cyano, carboxyle, 1-4C-alkyle, 1-4C-alkoxy, 1-4C-alkoxycarbonyle ou amino, R7 est hydrogène, halogène, amino ou 1-4C-alkyle, R8 est hydrogène ou halogène et R9 is hydrogène ou halogène, les sels de ce composé, les N-oxydes des pyridines et leurs sels sont des produits à action thérapeutique sur les bronches.
• Development of New Deoxycytidine Kinase Inhibitors and Noninvasive in Vivo Evaluation Using Positron Emission Tomography
  作者：Jennifer M. Murphy、Amanda L. Armijo、Julian Nomme、Chi Hang Lee、Quentin A. Smith、Zheng Li、Dean O. Campbell、Hsiang-I Liao、David A. Nathanson、Wayne R. Austin、Jason T. Lee、Ryan Darvish、Liu Wei、Jue Wang、Ying Su、Robert Damoiseaux、Saman Sadeghi、Michael E. Phelps、Harvey R. Herschman、Johannes Czernin、Anastassia N. Alexandrova、Michael E. Jung、Arnon Lavie、Caius G. Radu

  DOI：10.1021/jm400457y

  日期：2013.9.12

  Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest, and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure activity relationship study was carried out Positron Emission Tomography (PET) using F-18-L-1-(2'-deoxy-2':-FluoroArabinofuranosyl) Cytosine (F-18-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC50 = similar to 1-12 nM) using the F-18-L-FAC PET pharmacodynatnic assay identified compounds demonstrating superior in vivo efficacy.