2-amino-2-(3-fluoro-4-hydroxyphenyl)acetonitrile | 1208237-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2-amino-2-(3-fluoro-4-hydroxyphenyl)acetonitrile
• 英文别名: 2-Amino-2-(3-fluoro-4-hydroxyphenyl)acetonitrile
• CAS: 1208237-24-4
• 化学式: C₈H₇FN₂O
• 分子量: 166.155
• InChiKey: CNELZDXAKSSZQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-2-(3-fluoro-4-hydroxyphenyl)acetonitrile 在 盐酸 、 水 作用下， 反应 5.0h， 以70%的产率得到2-(3-fluoro-4-hydroxyphenyl)glycine hydrochloride
  参考文献：
  名称：

  Bioisosterism of urea-based GCPII inhibitors: Synthesis and structure–activity relationship studies

  摘要：

  We report a strategy based on bioisosterism to improve the physicochemical properties of existing hydrophilic, urea-based GCPII inhibitors. Comprehensive structure-activity relationship studies of the P1' site of ZJ-43- and DCIBzL-based compounds identified several glutamate-free inhibitors with K-i values below 20 nM. Among them, compound 32d (K-i = 11 nM) exhibited selective uptake in GCPII-expressing tumors by SPECT-CT imaging in mice. A novel conformational change of amino acids in the S1' pharmacophore pocket was observed in the X-ray crystal structure of GCPII complexed with 32d. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.061
• 作为产物：
  描述：

  三甲基氰硅烷 、 3-氟-4-羟基苯甲醛 在 氨 作用下， 以 甲醇 为溶剂， 反应 5.17h， 以40%的产率得到2-amino-2-(3-fluoro-4-hydroxyphenyl)acetonitrile
  参考文献：
  名称：

  Bioisosterism of urea-based GCPII inhibitors: Synthesis and structure–activity relationship studies

  摘要：

  We report a strategy based on bioisosterism to improve the physicochemical properties of existing hydrophilic, urea-based GCPII inhibitors. Comprehensive structure-activity relationship studies of the P1' site of ZJ-43- and DCIBzL-based compounds identified several glutamate-free inhibitors with K-i values below 20 nM. Among them, compound 32d (K-i = 11 nM) exhibited selective uptake in GCPII-expressing tumors by SPECT-CT imaging in mice. A novel conformational change of amino acids in the S1' pharmacophore pocket was observed in the X-ray crystal structure of GCPII complexed with 32d. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.061

文献信息

• Bioisosterism of urea-based GCPII inhibitors: Synthesis and structure–activity relationship studies
  作者：Haofan Wang、Youngjoo Byun、Cyril Barinka、Mrudula Pullambhatla、Hyo-eun C. Bhang、James J. Fox、Jacek Lubkowski、Ronnie C. Mease、Martin G. Pomper

  DOI：10.1016/j.bmcl.2009.10.061

  日期：2010.1

  We report a strategy based on bioisosterism to improve the physicochemical properties of existing hydrophilic, urea-based GCPII inhibitors. Comprehensive structure-activity relationship studies of the P1' site of ZJ-43- and DCIBzL-based compounds identified several glutamate-free inhibitors with K-i values below 20 nM. Among them, compound 32d (K-i = 11 nM) exhibited selective uptake in GCPII-expressing tumors by SPECT-CT imaging in mice. A novel conformational change of amino acids in the S1' pharmacophore pocket was observed in the X-ray crystal structure of GCPII complexed with 32d. (C) 2009 Elsevier Ltd. All rights reserved.