2-[3-(2-{1-[4-(6-{[2-(6-aminopurin-9-yl)-4-hydroxy-5-thiophosphonooxymethyltetrahydrofuran-3-yloxy]hydroxythiophosphoryloxy}hexylcarbamoyl)cyclohexylmethyl]-2,5-dioxopyrrolidin-3-ylsulfanyl}-1-carboxyethyl)ureido]pentanedioic acid | 1374847-87-6

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 2-[3-(2-{1-[4-(6-{[2-(6-aminopurin-9-yl)-4-hydroxy-5-thiophosphonooxymethyltetrahydrofuran-3-yloxy]hydroxythiophosphoryloxy}hexylcarbamoyl)cyclohexylmethyl]-2,5-dioxopyrrolidin-3-ylsulfanyl}-1-carboxyethyl)ureido]pentanedioic acid
• CAS: 1374847-87-6
• 化学式: C₃₇H₅₅N₉O₁₈P₂S₃
• 分子量: 1072.04
• InChiKey: QNTYUWYZYCVEER-ZESFMDLTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.75
• 重原子数：
  69.0
• 可旋转键数：
  27.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  403.81
• 氢给体数：
  11.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  2-[3-(2-{1-[4-(6-{[2-(6-aminopurin-9-yl)-4-hydroxy-5-thiophosphonooxymethyltetrahydrofuran-3-yloxy]hydroxythiophosphoryloxy}hexylcarbamoyl)cyclohexylmethyl]-2,5-dioxopyrrolidin-3-ylsulfanyl}-1-carboxyethyl)ureido]pentanedioic acid 、 2-bromo-N-(4-fluorobenzyl)acetamide 以 甲醇 为溶剂， 反应 0.5h， 以91.3%的产率得到2-[({2-[(1-{[4-({6-[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-[({[({[(4-fluorophenyl)methyl]carbamoyl}methyl)sulfanyl](hydroxy)phosphoryl}oxy)methyl]-4-hydroxyoxolan-3-yl]oxy}(hydroxy)sulfanylidenephosphanyl)oxy]hexyl} carbamoyl)cyclohexyl]methyl}-2,5-dioxopyrrolidin-3-yl)sulfanyl]-1-carboxyethyl} carbamoyl)amino]pentanedioic acid
  参考文献：
  名称：

  Structure-Activity Relationships of 2′,5′-Oligoadenylate Analogue Modifications of Prostate-Specific Membrane Antigen (PSMA) Antagonists

  摘要：

  Prostate-specific membrane antigen (PSMA) is an ideal biomarker for prostate cancer. A previously reported 2-5A conjugate RBI1033 (3) showed binding affinity more than 10 times higher than the parent urea-based compound (S)-2-(3-((S)-5-amino-1-carboxypentyl) ureido) pentanedioic acid (1). The purpose of this work is to further optimize the structure of 3 to identify highly selective ligands of PSMA. It was found that conjugates having 2-5A in their structure showed extraordinary improved binding affinity to PSMA compared with compound 1. Removal of 2-5A significantly reduced its biological activity. The results will provide a path to agents for targeted imaging and treatment of prostate cancer.

  DOI：

  10.1080/15257770.2012.671988
• 作为产物：
  描述：

  (S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido)pentanedioic acid 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-[3-(2-{1-[4-(6-{[2-(6-aminopurin-9-yl)-4-hydroxy-5-thiophosphonooxymethyltetrahydrofuran-3-yloxy]hydroxythiophosphoryloxy}hexylcarbamoyl)cyclohexylmethyl]-2,5-dioxopyrrolidin-3-ylsulfanyl}-1-carboxyethyl)ureido]pentanedioic acid
  参考文献：
  名称：

  Structure-Activity Relationships of 2′,5′-Oligoadenylate Analogue Modifications of Prostate-Specific Membrane Antigen (PSMA) Antagonists

  摘要：

  Prostate-specific membrane antigen (PSMA) is an ideal biomarker for prostate cancer. A previously reported 2-5A conjugate RBI1033 (3) showed binding affinity more than 10 times higher than the parent urea-based compound (S)-2-(3-((S)-5-amino-1-carboxypentyl) ureido) pentanedioic acid (1). The purpose of this work is to further optimize the structure of 3 to identify highly selective ligands of PSMA. It was found that conjugates having 2-5A in their structure showed extraordinary improved binding affinity to PSMA compared with compound 1. Removal of 2-5A significantly reduced its biological activity. The results will provide a path to agents for targeted imaging and treatment of prostate cancer.

  DOI：

  10.1080/15257770.2012.671988