2-[({2-[(1-{[4-({6-[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-({[hydroxy(sulfanyl)phosphoryl]oxy}methyl)oxolan-3-yl]oxy} (hydroxy)sulfanylidene-phosphanyl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy)-sulfanylidene-phosphanyl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy) sulfanylidene-phosphanyl)oxy]hexyl}carbamoyl)cyclohexyl]methyl}-2,5-dioxopyrrolidin-3-yl)sulfanyl]-1-carboxyethyl}carbamoyl)amino]pentanedioic acid | 1374847-88-7

• 分子结构分类: 有机化合物
• 英文名称: 2-[({2-[(1-{[4-({6-[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-({[hydroxy(sulfanyl)phosphoryl]oxy}methyl)oxolan-3-yl]oxy} (hydroxy)sulfanylidene-phosphanyl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy)-sulfanylidene-phosphanyl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy) sulfanylidene-phosphanyl)oxy]hexyl}carbamoyl)cyclohexyl]methyl}-2,5-dioxopyrrolidin-3-yl)sulfanyl]-1-carboxyethyl}carbamoyl)amino]pentanedioic acid
• CAS: 1374847-88-7
• 化学式: C₅₇H₇₉N₁₉O₂₈P₄S₅
• 分子量: 1762.59
• InChiKey: VFMKDPZIFNESCT-SGVJFSINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.66
• 重原子数：
  113.0
• 可旋转键数：
  39.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  679.35
• 氢给体数：
  17.0
• 氢受体数：
  40.0

反应信息

• 作为反应物：
  描述：

  2-[({2-[(1-{[4-({6-[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-({[hydroxy(sulfanyl)phosphoryl]oxy}methyl)oxolan-3-yl]oxy} (hydroxy)sulfanylidene-phosphanyl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy)-sulfanylidene-phosphanyl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy) sulfanylidene-phosphanyl)oxy]hexyl}carbamoyl)cyclohexyl]methyl}-2,5-dioxopyrrolidin-3-yl)sulfanyl]-1-carboxyethyl}carbamoyl)amino]pentanedioic acid 、 2-bromo-N-(4-fluorobenzyl)acetamide 以 甲醇 为溶剂， 反应 0.5h， 以86.3%的产率得到{[(2R,5R)-5-(6-amino-9H-purin-9-yl)-4-[({[(2R,5R)-5-(6-amino-9H-purin-9-yl)-4-[({[(2R,5R)-5-(6-amino-9H-purin-9-yl)-3-hydroxy-4-{[hydroxy(sulfanylidene)phosphanyl]oxy}oxolan-2-yl]methoxy}(hydroxy)sulfanylidenephosphanyl)oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)sulfanylidenephosphanyl)oxy]-3-hydroxyoxolan-2-yl]methoxy}[({[(4-fluorophenyl)methyl]carbamoyl}methyl)sulfanyl]phosphinic 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：

  (((1S)-1-carboxy-2-((1-((4-(((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)cyclohexyl)methyl)-2,5-dioxopyrrolidin-3-yl)thio)ethyl)carbamoyl)-L-glutamic acid 、 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-[({2-[(1-{[4-({6-[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-5-{[({[(2R,5R)-2-(6-amino-9H-purin-9-yl)-4-hydroxy-5-({[hydroxy(sulfanyl)phosphoryl]oxy}methyl)oxolan-3-yl]oxy} (hydroxy)sulfanylidene-phosphanyl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy)-sulfanylidene-phosphanyl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy) sulfanylidene-phosphanyl)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