O⁶-(4-formylbenzyl)guanine | 152832-97-8

• 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-(4-formylbenzyl)guanine
• 英文别名: O⁶-(p-formylbenzyl)guanine；4-[(2-amino-7H-purin-6-yl)oxymethyl]benzaldehyde
• CAS: 152832-97-8
• 化学式: C₁₃H₁₁N₅O₂
• 分子量: 269.263
• InChiKey: GQUWKGQZTWHIIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  O⁶-(4-formylbenzyl)guanine 在 4-二甲氨基吡啶 、 氢氧化钾 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.0h， 生成 N2,9-bis-(p-anisyldiphenylmethyl)-O6-[4-(2-fluoroethoxymethyl)benzyl]guanine
  参考文献：
  名称：

  Synthesis and preliminary biological evaluation of O6-[4-(2-[18F]fluoroethoxymethyl)benzyl]guanine as a novel potential PET probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase in cancer chemotherapy

  摘要：

  A novel fluorine- 18-labeled O-6 -benzylguanine (O-6-BG) derivative, 0(6)-[4-(2-[F-18]fluoroetboxymethyl)benzyl[guanine (O-6-[F-18]FEMBG, [[F-18]1), has been synthesized for evaluation as a potential positron emission tomography (PET) probe for the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (AGT) in cancer chemotherapy. The appropriate radiolabeling precursor N-2,(9)-bis(p-anisyldiphenylmethyl)-O-6-[4-(hydroxymethyl)benzyl]guanine (6) and reference standard O-6-[4-(2-fluoroethoxymethyl)benzyl]guanine (O-6 -FEMBG, 1) were synthesized from 1,4-benzenedimethanol and 2-amino-6-chloropurine in four or six steps, respectively, with moderate to excellent chemical yields. The target tracer O-6-[F-18]FEMBG was prepared in 20-35% radiochemical yields by reaction of MTr-protected precursor 6 with [F-18]fluoroethyl bromide followed by quick deprotection reaction and purification with a simplified Silica Sep-Pak method. Total synthesis time was 60-70 min from the end of bombardment. Radiochemical purity of the formulated product was >95%, with a specific radioactivity of >1.0 Ci/mu mol at the end of synthesis. The activity of unlabeled O-6-FEMBG was evaluated via an in vitro AGT oligonucleotide assay. Preliminary findings from biological assay indicate that the synthesized analogue has similarly strong inhibiting effect on AGT in comparison with O-6-BG and O-6-4-fluorobenzylguanine (O-6-FBG). The results warrant further in vivo evaluation of O-6-[F-18]FEMBG as a new potential PET probe for AGT. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.061
• 作为产物：
  描述：

  对苯二甲醇 在 吡啶 、 sodium acetate 、 sodium 、 pyridinium chlorochromate 作用下， 反应 24.0h， 生成 O⁶-(4-formylbenzyl)guanine
  参考文献：
  名称：

  Synthesis and preliminary biological evaluation of O6-[4-(2-[18F]fluoroethoxymethyl)benzyl]guanine as a novel potential PET probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase in cancer chemotherapy

  摘要：

  A novel fluorine- 18-labeled O-6 -benzylguanine (O-6-BG) derivative, 0(6)-[4-(2-[F-18]fluoroetboxymethyl)benzyl[guanine (O-6-[F-18]FEMBG, [[F-18]1), has been synthesized for evaluation as a potential positron emission tomography (PET) probe for the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (AGT) in cancer chemotherapy. The appropriate radiolabeling precursor N-2,(9)-bis(p-anisyldiphenylmethyl)-O-6-[4-(hydroxymethyl)benzyl]guanine (6) and reference standard O-6-[4-(2-fluoroethoxymethyl)benzyl]guanine (O-6 -FEMBG, 1) were synthesized from 1,4-benzenedimethanol and 2-amino-6-chloropurine in four or six steps, respectively, with moderate to excellent chemical yields. The target tracer O-6-[F-18]FEMBG was prepared in 20-35% radiochemical yields by reaction of MTr-protected precursor 6 with [F-18]fluoroethyl bromide followed by quick deprotection reaction and purification with a simplified Silica Sep-Pak method. Total synthesis time was 60-70 min from the end of bombardment. Radiochemical purity of the formulated product was >95%, with a specific radioactivity of >1.0 Ci/mu mol at the end of synthesis. The activity of unlabeled O-6-FEMBG was evaluated via an in vitro AGT oligonucleotide assay. Preliminary findings from biological assay indicate that the synthesized analogue has similarly strong inhibiting effect on AGT in comparison with O-6-BG and O-6-4-fluorobenzylguanine (O-6-FBG). The results warrant further in vivo evaluation of O-6-[F-18]FEMBG as a new potential PET probe for AGT. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.061

文献信息

• Substituted O6-Benzylguanine Derivatives and Their Inactivation of Human O6-Alkylguanine-DNA Alkyltransferase
  作者：Mi Young Chae、Mark G. McDougall、M. Eileen Dolan、Kristin Swenn、Anthony E. Pegg、Robert C. Moschel

  DOI：10.1021/jm00029a005

  日期：1994.2

  Several new O-6-benzylguanine analogs bearing increasingly bulky substituent groups on the benzene ring or at position 9 were tested for their ability to inactivate the human DNA repair protein, O-6-alkylguanine-DNA alkyltransferase. Substitution on the benzene ring was well tolerated although activity varied considerably with structural changes in groups attached to position 9. For this site, activity was preserved with large or small lipophilic groups while introduction of non-carbohydrate polar groups generally reduced activity regardless of their size.
• Synthesis and preliminary biological evaluation of O6-[4-(2-[18F]fluoroethoxymethyl)benzyl]guanine as a novel potential PET probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase in cancer chemotherapy
  作者：Ji-Quan Wang、Emiko L. Kreklau、Barbara J. Bailey、Leonard C. Erickson、Qi-Huang Zheng

  DOI：10.1016/j.bmc.2005.05.061

  日期：2005.10

  A novel fluorine- 18-labeled O-6 -benzylguanine (O-6-BG) derivative, 0(6)-[4-(2-[F-18]fluoroetboxymethyl)benzyl[guanine (O-6-[F-18]FEMBG, [[F-18]1), has been synthesized for evaluation as a potential positron emission tomography (PET) probe for the DNA repair protein O-6-alkylguanine-DNA alkyltransferase (AGT) in cancer chemotherapy. The appropriate radiolabeling precursor N-2,(9)-bis(p-anisyldiphenylmethyl)-O-6-[4-(hydroxymethyl)benzyl]guanine (6) and reference standard O-6-[4-(2-fluoroethoxymethyl)benzyl]guanine (O-6 -FEMBG, 1) were synthesized from 1,4-benzenedimethanol and 2-amino-6-chloropurine in four or six steps, respectively, with moderate to excellent chemical yields. The target tracer O-6-[F-18]FEMBG was prepared in 20-35% radiochemical yields by reaction of MTr-protected precursor 6 with [F-18]fluoroethyl bromide followed by quick deprotection reaction and purification with a simplified Silica Sep-Pak method. Total synthesis time was 60-70 min from the end of bombardment. Radiochemical purity of the formulated product was >95%, with a specific radioactivity of >1.0 Ci/mu mol at the end of synthesis. The activity of unlabeled O-6-FEMBG was evaluated via an in vitro AGT oligonucleotide assay. Preliminary findings from biological assay indicate that the synthesized analogue has similarly strong inhibiting effect on AGT in comparison with O-6-BG and O-6-4-fluorobenzylguanine (O-6-FBG). The results warrant further in vivo evaluation of O-6-[F-18]FEMBG as a new potential PET probe for AGT. (c) 2005 Elsevier Ltd. All rights reserved.