5'-azido-5'-deoxy-2',3'-bis-O-triisopropylsilyladenosine | 1401415-28-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-azido-5'-deoxy-2',3'-bis-O-triisopropylsilyladenosine
• 英文别名: 9-[(2R,3R,4R,5R)-5-(azidomethyl)-3,4-bis[tri(propan-2-yl)silyloxy]oxolan-2-yl]purin-6-amine
• CAS: 1401415-28-8
• 化学式: C₂₈H₅₂N₈O₃Si₂
• 分子量: 604.944
• InChiKey: BVINLXAJTFDPEO-ZYWWQZICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.74
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-azido-5'-deoxy-2',3'-bis-O-triisopropylsilyladenosine 在 10% Pd/C 、 氢气 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 168.0h， 生成 1-methyl-3-[[(2R,3R,4R,5R)-5-[6-(phenylcarbamoylamino)purin-9-yl]-3,4-bis[tri(propan-2-yl)silyloxy]oxolan-2-yl]methyl]urea
  参考文献：
  名称：

  Synthesis and SAR of 2′,3′-bis-O-substituted N6, 5′-bis-ureidoadenosine derivatives: Implications for prodrug delivery and mechanism of action

  摘要：

  A series of 2',3'-bis-O-silylated or -acylated derivatives of lead compound 3a (2',3'-bis-O-tert-butyl-dimethylsilyl-5'-deoxy-5'-(N-methylcarbamoyl)amino-N-6-(N-phenylcarbamoyl)adenosine) were prepared and evaluated for antiproliferative activity against a panel of murine and human cancer cell lines (L1210, FM3A, CEM, and HeLa). 2',3'-O-Silyl groups investigated included triethylsilyl (10a), tert-butyldiphenylsilyl (10b), and triisopropylsilyl (10c). 2',3'-O-Acyl groups investigated included acetyl (13a), benzoyl (13b), isobutyryl (13c), butanoyl (13d), pivaloyl (13e), hexanoyl (13f), octanoyl (13g), decanoyl (13h), and hexadecanoyl (13i). IC50 values ranged from 3.0 +/- 0.3 to > 200 mu g/mL, with no improvement relative to lead compound 3a. Derivative 10a was approximately equipotent to 3a, while compounds 13e-g were from three to fivefold less potent, and all other compounds were significantly much less active. A desilylated derivative (5'-deoxy-5'-(N-methylcarbamoyl) amino-N-6-(N-phenylcarbamoyl) adenosine; 5) and several representative derivatives from each subgroup (10a-10c, 13a-13c) were screened for binding affinity for bone morphogenetic protein receptor 1b (BMPR1b). Only compound 5 showed appreciable affinity (K-d = 11.7 +/- 0.5 mu M), consistent with the inference that 3a may act as a prodrug depot form of the biologically active derivative 5. Docking studies (Surflex Dock, Sybyl X 1.3) for compounds 3a and 5 support this conclusion. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.050
• 作为产物：
  描述：

  三异丙基氯硅烷 、 5'-氯-5'-脱氧腺苷 在 sodium azide 、 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 以42%的产率得到5'-azido-5'-deoxy-2',3'-bis-O-triisopropylsilyladenosine
  参考文献：
  名称：

  Synthesis and SAR of 2′,3′-bis-O-substituted N6, 5′-bis-ureidoadenosine derivatives: Implications for prodrug delivery and mechanism of action

  摘要：

  A series of 2',3'-bis-O-silylated or -acylated derivatives of lead compound 3a (2',3'-bis-O-tert-butyl-dimethylsilyl-5'-deoxy-5'-(N-methylcarbamoyl)amino-N-6-(N-phenylcarbamoyl)adenosine) were prepared and evaluated for antiproliferative activity against a panel of murine and human cancer cell lines (L1210, FM3A, CEM, and HeLa). 2',3'-O-Silyl groups investigated included triethylsilyl (10a), tert-butyldiphenylsilyl (10b), and triisopropylsilyl (10c). 2',3'-O-Acyl groups investigated included acetyl (13a), benzoyl (13b), isobutyryl (13c), butanoyl (13d), pivaloyl (13e), hexanoyl (13f), octanoyl (13g), decanoyl (13h), and hexadecanoyl (13i). IC50 values ranged from 3.0 +/- 0.3 to > 200 mu g/mL, with no improvement relative to lead compound 3a. Derivative 10a was approximately equipotent to 3a, while compounds 13e-g were from three to fivefold less potent, and all other compounds were significantly much less active. A desilylated derivative (5'-deoxy-5'-(N-methylcarbamoyl) amino-N-6-(N-phenylcarbamoyl) adenosine; 5) and several representative derivatives from each subgroup (10a-10c, 13a-13c) were screened for binding affinity for bone morphogenetic protein receptor 1b (BMPR1b). Only compound 5 showed appreciable affinity (K-d = 11.7 +/- 0.5 mu M), consistent with the inference that 3a may act as a prodrug depot form of the biologically active derivative 5. Docking studies (Surflex Dock, Sybyl X 1.3) for compounds 3a and 5 support this conclusion. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.050

文献信息

• Synthesis and SAR of 2′,3′-bis-O-substituted N6, 5′-bis-ureidoadenosine derivatives: Implications for prodrug delivery and mechanism of action
  作者：Jadd R. Shelton、Christopher E. Cutler、Megan S. Browning、Jan Balzarini、Matt A. Peterson

  DOI：10.1016/j.bmcl.2012.08.050

  日期：2012.10

  A series of 2',3'-bis-O-silylated or -acylated derivatives of lead compound 3a (2',3'-bis-O-tert-butyl-dimethylsilyl-5'-deoxy-5'-(N-methylcarbamoyl)amino-N-6-(N-phenylcarbamoyl)adenosine) were prepared and evaluated for antiproliferative activity against a panel of murine and human cancer cell lines (L1210, FM3A, CEM, and HeLa). 2',3'-O-Silyl groups investigated included triethylsilyl (10a), tert-butyldiphenylsilyl (10b), and triisopropylsilyl (10c). 2',3'-O-Acyl groups investigated included acetyl (13a), benzoyl (13b), isobutyryl (13c), butanoyl (13d), pivaloyl (13e), hexanoyl (13f), octanoyl (13g), decanoyl (13h), and hexadecanoyl (13i). IC50 values ranged from 3.0 +/- 0.3 to > 200 mu g/mL, with no improvement relative to lead compound 3a. Derivative 10a was approximately equipotent to 3a, while compounds 13e-g were from three to fivefold less potent, and all other compounds were significantly much less active. A desilylated derivative (5'-deoxy-5'-(N-methylcarbamoyl) amino-N-6-(N-phenylcarbamoyl) adenosine; 5) and several representative derivatives from each subgroup (10a-10c, 13a-13c) were screened for binding affinity for bone morphogenetic protein receptor 1b (BMPR1b). Only compound 5 showed appreciable affinity (K-d = 11.7 +/- 0.5 mu M), consistent with the inference that 3a may act as a prodrug depot form of the biologically active derivative 5. Docking studies (Surflex Dock, Sybyl X 1.3) for compounds 3a and 5 support this conclusion. (C) 2012 Elsevier Ltd. All rights reserved.