{[(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)-4-[({[6-({4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]cyclohexyl}formamido)hexyl]oxy}(hydroxy)phosphoryl)-oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}phosphonic acid | 1374847-68-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: {[(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)-4-[({[6-({4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]cyclohexyl}formamido)hexyl]oxy}(hydroxy)phosphoryl)-oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}phosphonic acid
• CAS: 1374847-68-3
• 化学式: C₄₈H₆₅N₁₇O₂₅P₄
• 分子量: 1404.04
• InChiKey: SRIPQZQDEDOTTJ-DNGLURHESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.95
• 重原子数：
  94.0
• 可旋转键数：
  29.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  597.76
• 氢给体数：
  12.0
• 氢受体数：
  35.0

反应信息

• 作为反应物：
  描述：

  {[(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)-4-[({[6-({4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]cyclohexyl}formamido)hexyl]oxy}(hydroxy)phosphoryl)-oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}phosphonic acid 、 (S)-2-(3-((S)-5-amino-1-carboxypentyl)ureido)pentanedioic acid 反应 1.0h， 以90%的产率得到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-[(phosphonooxy)methyl]oxolan-3-yl]oxy}(hydroxy)phosphoryl)oxy]methyl}-4-hy-droxyoxolan-3-yl]oxy}(hydroxy)phosphoryl)oxy]methyl}-4-hydroxyoxolan-3-yl]oxy} (hydroxy)phosphoryl)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：

  4-(N-马来酰亚胺基甲基)环己烷-1-羧酸琥珀酰亚胺酯 、 2',5'-oligoadenylate trimer{[(2R,5R)-5-(6-amino-9H-purin-9-yl)-4-[({[2R,5R-5-(6-amino-9H-purin-yl)-4-[({[2R,5R-5-(6-amino-9H-purinyl)-4-({[(6-aminohexyl)oxy](hydroxy)phosphoryl}oxy)-3-hydroxyoxolan-2-yl]-methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}phosphonic acid 以72.8%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)-4-[({[6-({4-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl]cyclohexyl}formamido)hexyl]oxy}(hydroxy)phosphoryl)-oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]-3-hydroxyoxolan-2-yl]methoxy}phosphonic 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