[(2R,3R,4S,5R,6R)-6-[8-[2-amino-6-[(5-iodothiophen-2-yl)methoxy]purin-9-yl]octoxy]-3,4,5-tribenzoyloxyoxan-2-yl]methyl benzoate | 875584-27-3

• 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: [(2R,3R,4S,5R,6R)-6-[8-[2-amino-6-[(5-iodothiophen-2-yl)methoxy]purin-9-yl]octoxy]-3,4,5-tribenzoyloxyoxan-2-yl]methyl benzoate
• CAS: 875584-27-3
• 化学式: C₅₂H₅₀IN₅O₁₁S
• 分子量: 1079.97
• InChiKey: SETGUTCXJWAUOC-LJKMPDPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.5
• 重原子数：
  70
• 可旋转键数：
  26
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  231
• 氢给体数：
  1
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4S,5R,6R)-6-[8-[2-amino-6-[(5-iodothiophen-2-yl)methoxy]purin-9-yl]octoxy]-3,4,5-tribenzoyloxyoxan-2-yl]methyl benzoate 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以56%的产率得到(2R,3R,4S,5S,6R)-2-[8-[2-amino-6-[(5-iodothiophen-2-yl)methoxy]purin-9-yl]octoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
  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-噻吩甲醇 在 4 A molecular sieve 、 碘 、 lithium hydride 、 sodium hydride 、 mercury(II) oxide 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 101.0h， 生成 [(2R,3R,4S,5R,6R)-6-[8-[2-amino-6-[(5-iodothiophen-2-yl)methoxy]purin-9-yl]octoxy]-3,4,5-tribenzoyloxyoxan-2-yl]methyl benzoate
  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