(S)-2-(3-((S)-5-(6-(4-(4-(4-acetylpiperazin-1-yl)phenyl)piperazin-1-yl)-N-(4-bromobenzyl)nicotinamido)-1-carboxypentyl)ureido)pentanedioic acid

• 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)-5-(6-(4-(4-(4-acetylpiperazin-1-yl)phenyl)piperazin-1-yl)-N-(4-bromobenzyl)nicotinamido)-1-carboxypentyl)ureido)pentanedioic acid
• 英文别名: (2S)-2-[[(1S)-5-[[6-[4-[4-(4-acetylpiperazin-1-yl)phenyl]piperazin-1-yl]pyridine-3-carbonyl]-[(4-bromophenyl)methyl]amino]-1-carboxypentyl]carbamoylamino]pentanedioic acid
• 化学式: C₄₁H₅₁BrN₈O₉
• 分子量: 879.808
• InChiKey: AQMMDCVVJLFRNY-PXLJZGITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  59
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  216
• 氢给体数：
  5
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  1-(4-碘苯基)哌嗪 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 potassium tert-butylate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 58.5h， 生成 (S)-2-(3-((S)-5-(6-(4-(4-(4-acetylpiperazin-1-yl)phenyl)piperazin-1-yl)-N-(4-bromobenzyl)nicotinamido)-1-carboxypentyl)ureido)pentanedioic acid
  参考文献：
  名称：

  Design of Highly Potent Urea-Based, Exosite-Binding Inhibitors Selective for Glutamate Carboxypeptidase II

  摘要：

  We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward, GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.

  DOI：

  10.1021/acs.jmedchem.5b00278

文献信息

• Design of Highly Potent Urea-Based, Exosite-Binding Inhibitors Selective for Glutamate Carboxypeptidase II
  作者：Jan Tykvart、Jiří Schimer、Andrej Jančařík、Jitka Bařinková、Václav Navrátil、Jana Starková、Karolína Šrámková、Jan Konvalinka、Pavel Majer、Pavel Šácha

  DOI：10.1021/acs.jmedchem.5b00278

  日期：2015.5.28

  We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward, GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.