(2S)-2-((3-(1R)-1-carboxy-2-((1-(S)-5-carboxy-5-(5-(3-iodobenzamido)pentanamido)pentyl-2,5-dioxopyrrolidin-3-yl)thio)ethyl)ureido)pentanedioic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (2S)-2-((3-(1R)-1-carboxy-2-((1-(S)-5-carboxy-5-(5-(3-iodobenzamido)pentanamido)pentyl-2,5-dioxopyrrolidin-3-yl)thio)ethyl)ureido)pentanedioic acid
• 英文别名: (2S)-2-[[(1R)-1-carboxy-2-[1-[(5S)-5-carboxy-5-[5-[(3-iodobenzoyl)amino]pentanoylamino]pentyl]-2,5-dioxopyrrolidin-3-yl]sulfanylethyl]carbamoylamino]pentanedioic acid
• 化学式: C₃₁H₄₀IN₅O₁₃S
• 分子量: 849.655
• InChiKey: SPWXRTXRMWKLDC-RQLHVLPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  51
• 可旋转键数：
  23
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  311
• 氢给体数：
  8
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  5-氨基颉草酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 14.0h， 生成 (2S)-2-((3-(1R)-1-carboxy-2-((1-(S)-5-carboxy-5-(5-(3-iodobenzamido)pentanamido)pentyl-2,5-dioxopyrrolidin-3-yl)thio)ethyl)ureido)pentanedioic acid
  参考文献：
  名称：

  Preparation of Asymmetric Urea Derivatives that Target Prostate-Specific Membrane Antigen for SPECT Imaging

  摘要：

  Prostate-specific membrane antigen (PSMA) has been identified as a diagnostic and therapeutic target for prostate cancer. (S)-2-[3-[(R)-1-Carboxy-2-mercaptoethyl]ureido-pentanedioic acid (Cys-CO-Glu) were used to design novel PSMA targeting probes by nucleophilic conjugate addition between cysteine and maleimide based reagents. 3 ([I-123]IGLCE) was synthesized by this strategy and showed high affinity for PSMA. Results of binding inhibition assays of these derivatives suggested the importance of an aromatic group and succinimide moiety for high affinity. [I-123]3 was evaluated in vivo with PSMA positive LNCaP and PSMA negative PC-3 human prostate cancer xenograft bearing mice. [I-125]3 accumulated in LNCaP tumors but not in PC-3 tumors, and the accumulation was inhibited by 2-(phosphonomethyl)pentanedioic acid (2-PMPA). Use of [I-123]3 provided positive images of LNCaP tumors in single photon emission tomography scans. These results warrant further evaluation of [I-123]3 and its derivatives as radiolabeled probes for the diagnosis of prostate cancer.

  DOI：

  10.1021/jm400895s

文献信息

• Preparation of Asymmetric Urea Derivatives that Target Prostate-Specific Membrane Antigen for SPECT Imaging
  作者：Naoya Harada、Hiroyuki Kimura、Masahiro Ono、Hideo Saji

  DOI：10.1021/jm400895s

  日期：2013.10.24

  Prostate-specific membrane antigen (PSMA) has been identified as a diagnostic and therapeutic target for prostate cancer. (S)-2-[3-[(R)-1-Carboxy-2-mercaptoethyl]ureido-pentanedioic acid (Cys-CO-Glu) were used to design novel PSMA targeting probes by nucleophilic conjugate addition between cysteine and maleimide based reagents. 3 ([I-123]IGLCE) was synthesized by this strategy and showed high affinity for PSMA. Results of binding inhibition assays of these derivatives suggested the importance of an aromatic group and succinimide moiety for high affinity. [I-123]3 was evaluated in vivo with PSMA positive LNCaP and PSMA negative PC-3 human prostate cancer xenograft bearing mice. [I-125]3 accumulated in LNCaP tumors but not in PC-3 tumors, and the accumulation was inhibited by 2-(phosphonomethyl)pentanedioic acid (2-PMPA). Use of [I-123]3 provided positive images of LNCaP tumors in single photon emission tomography scans. These results warrant further evaluation of [I-123]3 and its derivatives as radiolabeled probes for the diagnosis of prostate cancer.