2-amino-6-(3-iodobenzyloxy)-9-(octyltetra-O-benzoyl-β-D-glucopyranoside)purine | 875584-35-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-amino-6-(3-iodobenzyloxy)-9-(octyltetra-O-benzoyl-β-D-glucopyranoside)purine
• 英文别名: [(2R,3R,4S,5R,6R)-6-[8-[2-amino-6-[(3-iodophenyl)methoxy]purin-9-yl]octoxy]-3,4,5-tribenzoyloxyoxan-2-yl]methyl benzoate
• CAS: 875584-35-3
• 化学式: C₅₄H₅₂IN₅O₁₁
• 分子量: 1073.94
• InChiKey: BZXJVUKBCNXMPN-NERDCTGJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.7
• 重原子数：
  71
• 可旋转键数：
  26
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  203
• 氢给体数：
  1
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  2-amino-6-(3-iodobenzyloxy)-9-(octyltetra-O-benzoyl-β-D-glucopyranoside)purine 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以64%的产率得到2-amino-6-(3-iodobenzyloxy)-9-(octyl-β-D-glucopyranoside)purine
  参考文献：
  名称：

  Synthesis of ¹³¹I-Labeled Glucose-Conjugated Inhibitors of O⁶-Methylguanine-DNA Methyltransferase (MGMT) and Comparison with Nonconjugated Inhibitors as Potential Tools for in Vivo MGMT Imaging

  摘要：

  O-6-Substituted guanine derivatives are powerful agents used for tumor cell sensitization by inhibition of the DNA repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT). To provide targeted accumulation of MGMT inhibitors in tumor tissue as well as tools for in vivo imaging, we synthesized iodinated C-8-alkyl-linked glucose conjugates of 2-amino-6-(5-iodothenyl)-9H-purine (O-6-(5-iodothenyl) guanine, ITG) and 2-amino-6-(3-iodobenzyloxy)-9H-purine (O-6-(5-iodobenzyl) guanine, IBG). These compounds have MGMT inhibitor constants (IC50 values) of 0.8 and 0.45 mu M for ITGG and IBGG, respectively, as determined in HeLa S3 cells after 2-h incubation with inhibitor. To substantiate that the I-131-(hetero)arylmethylene group at the O-6-position of guanine is transferred to MGMT, both the glucose conjugated inhibitors ITGG and IBGG and the corresponding nonglucose conjugated compounds ITG and IBG were labeled with iodine-131. The radioiodinations of all compounds with [I-131]I- were performed with radiochemical yields of > 70% for the destannylation of the corresponding tri-n-butylstannylated precursors. The binding ability of [I-131]ITGG, [(131)]IBGG, [I-131]ITG, and [I-131]IBG to purified MGMT was tested. All radioactive compounds were substrates for MGMT, as demonstrated using a competitive repair assay. The newly synthesized radioactive inhibitors were utilized to study ex vivo biodistribution in mice, and the tumor-to-blood ratio of tissue uptake of [I-131]IBG and [I-131]IBGG was determined to be 0.24 and 0.76 after 0.5 h, respectively.

  DOI：

  10.1021/jm050588q
• 作为产物：
  描述：

  2,3,4,6-tetra-O-benzoylglucosyl bromide 在 4 A molecular sieve 、 三氟化硼乙醚 、 lithium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 110.0h， 生成 2-amino-6-(3-iodobenzyloxy)-9-(octyltetra-O-benzoyl-β-D-glucopyranoside)purine
  参考文献：
  名称：

  Synthesis of ¹³¹I-Labeled Glucose-Conjugated Inhibitors of O⁶-Methylguanine-DNA Methyltransferase (MGMT) and Comparison with Nonconjugated Inhibitors as Potential Tools for in Vivo MGMT Imaging

  摘要：

  O-6-Substituted guanine derivatives are powerful agents used for tumor cell sensitization by inhibition of the DNA repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT). To provide targeted accumulation of MGMT inhibitors in tumor tissue as well as tools for in vivo imaging, we synthesized iodinated C-8-alkyl-linked glucose conjugates of 2-amino-6-(5-iodothenyl)-9H-purine (O-6-(5-iodothenyl) guanine, ITG) and 2-amino-6-(3-iodobenzyloxy)-9H-purine (O-6-(5-iodobenzyl) guanine, IBG). These compounds have MGMT inhibitor constants (IC50 values) of 0.8 and 0.45 mu M for ITGG and IBGG, respectively, as determined in HeLa S3 cells after 2-h incubation with inhibitor. To substantiate that the I-131-(hetero)arylmethylene group at the O-6-position of guanine is transferred to MGMT, both the glucose conjugated inhibitors ITGG and IBGG and the corresponding nonglucose conjugated compounds ITG and IBG were labeled with iodine-131. The radioiodinations of all compounds with [I-131]I- were performed with radiochemical yields of > 70% for the destannylation of the corresponding tri-n-butylstannylated precursors. The binding ability of [I-131]ITGG, [(131)]IBGG, [I-131]ITG, and [I-131]IBG to purified MGMT was tested. All radioactive compounds were substrates for MGMT, as demonstrated using a competitive repair assay. The newly synthesized radioactive inhibitors were utilized to study ex vivo biodistribution in mice, and the tumor-to-blood ratio of tissue uptake of [I-131]IBG and [I-131]IBGG was determined to be 0.24 and 0.76 after 0.5 h, respectively.

  DOI：

  10.1021/jm050588q