N2,9-bis-(p-anisyldiphenylmethyl)-O6-(4-formylbenzyl)guanine | 868682-28-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N2,9-bis-(p-anisyldiphenylmethyl)-O6-(4-formylbenzyl)guanine
• 英文别名: N^2,9-bis-(p-anisyldiphenylmethyl)-O⁶-(4-formylbenzyl)guanine
• CAS: 868682-28-4
• 化学式: C₅₃H₄₃N₅O₄
• 分子量: 813.956
• InChiKey: BZCYDLHZVARXQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.48
• 重原子数：
  62.0
• 可旋转键数：
  15.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  100.39
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N2,9-bis-(p-anisyldiphenylmethyl)-O6-(4-formylbenzyl)guanine 在 盐酸 、 氢氧化钾 、 sodium tetrahydroborate 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 3.33h， 生成 6-[[4-(2-fluoroethoxymethyl)phenyl]methoxy]-7H-purin-2-amine
  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 、 4-二甲氨基吡啶 、 sodium acetate 、 sodium 、 三乙胺 、 pyridinium chlorochromate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 N2,9-bis-(p-anisyldiphenylmethyl)-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