(S)-2-(3-((S)-carboxy(4-hydroxyphenyl)methyl)ureido)-6-(4-iodobenzamido)hexanoic acid | 1348765-55-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-(3-((S)-carboxy(4-hydroxyphenyl)methyl)ureido)-6-(4-iodobenzamido)hexanoic acid
• 英文别名: N~2~-{[(S)-Carboxy(4-Hydroxyphenyl)methyl]carbamoyl}-N~6~-(4-Iodobenzoyl)-L-Lysine；(2S)-2-[[(S)-carboxy-(4-hydroxyphenyl)methyl]carbamoylamino]-6-[(4-iodobenzoyl)amino]hexanoic acid
• CAS: 1348765-55-8
• 化学式: C₂₂H₂₄IN₃O₇
• 分子量: 569.353
• InChiKey: GVEULWULTXBFPM-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  165
• 氢给体数：
  6
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (2,5-二氧代吡咯烷-1-基)4-碘苯甲酸酯 、 (2S,6S)-6-(tert-butoxycarbonyl)-2-(4-hydroxyphenyl)-14,14-dimethyl-4,12-dioxo-13-oxa-3,5,11-triazapentadecanoic acid 在 三氟乙酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 (S)-2-(3-((S)-carboxy(4-hydroxyphenyl)methyl)ureido)-6-(4-iodobenzamido)hexanoic acid
  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.