O⁶-(5-iodothenyl)guanine | 793035-52-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: O⁶-(5-iodothenyl)guanine
• 英文别名: 6-[(5-iodothiophen-2-yl)methoxy]-7H-purin-2-amine
• CAS: 793035-52-6
• 化学式: C₁₀H₈IN₅OS
• 分子量: 373.177
• InChiKey: GHNFXLRNWZSYBY-UHFFFAOYSA-N

物化性质

• 沸点：
  686.2±65.0 °C(Predicted)
• 密度：
  2.072±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O⁶-(5-iodothenyl)guanine 在 4 A molecular sieve 、 sodium methylate 、 lithium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 (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 碘 、 sodium hydride 、 mercury(II) oxide 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 77.0h， 生成 O⁶-(5-iodothenyl)guanine
  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

文献信息

• MGMT INHIBITOR COMBINATION FOR THE TREATMENT OF NEOPLASTIC DISORDERS
  申请人：Liu Lili

  公开号：US20100093647A1

  公开（公告）日：2010-04-15

  A method of treating a neoplastic disease in a subject includes administering to neoplastic cells of the subject an MGMT inhibitor and at least one of an antimitotic agent or a DNA damaging agent.
• Delivery System for Enhancing Drug Efficacy
  申请人：CLEMSON UNIVERSITY

  公开号：US20130236504A1

  公开（公告）日：2013-09-12

  Disclosed are delivery systems that can be used for treating cancer. The delivery systems include a delivery vehicle in conjunction with a chemo-adjuvant. The chemo-adjuvant can enhance the efficacy of a therapeutic agent that can be delivered in conjunction with the delivery vehicle or can be delivered independently of the delivery vehicle.
• MGMT INHIBITOR COMBINATIONS FOR THE TREATMENT OF NEOPLASTIC DISORDERS
  申请人：Case Western Reserve University

  公开号：US20140296264A1

  公开（公告）日：2014-10-02

  A method of treating a neoplastic disease in a subject includes administering to neoplastic cells of the subject an MGMT inhibitor and at least one of an antimitotic agent or a DNA damaging agent.
• US8791081B2
  申请人：——

  公开号：US8791081B2

  公开（公告）日：2014-07-29
• [EN] DELIVERY SYSTEMS FOR ENHANCING DRUG EFFICACY<br/>[FR] SYSTÈMES D'ADMINISTRATION POUR AMÉLIORER L'EFFICACITÉ D'UN MÉDICAMENT
  申请人：UNIV CLEMSON

  公开号：WO2013134349A1

  公开（公告）日：2013-09-12

  Disclosed are delivery systems that can be used for treating cancer. The delivery systems include a delivery vehicle in conjunction with a chemo-adjuvant. The chemo-adjuvant can enhance the efficacy of a therapeutic agent that can be delivered in conjunction with the delivery vehicle or can be delivered independently of the delivery vehicle.