O⁶-[(3-methyl)benzyl]guanine

• 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-[(3-methyl)benzyl]guanine
• 英文别名: O6-(m-methylbenzyl)guanine；O6-Substituted Guanine Deriv. 32；6-[(3-methylphenyl)methoxy]-7H-purin-2-amine
• 化学式: C₁₃H₁₃N₅O
• 分子量: 255.279
• InChiKey: WSSNDTDMMVLPHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  89.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  鸟嘌呤 在 溶剂黄146 、 三氯氧磷 作用下， 以 二甲基亚砜 、 1,2-二氯乙烷 、 PEG-2000 为溶剂， 反应 25.83h， 生成 O⁶-[(3-methyl)benzyl]guanine
  参考文献：
  名称：

  Hu, Yu Lin; Ge, Qiang; Lu, Ming, Bulletin of the Chemical Society of Ethiopia, 2010, vol. 24, # 3, p. 425 - 432

  摘要：

  DOI：

文献信息

• Synthesis of PET probe O6-[(3-[11C]methyl)benzyl]guanine by Pd0-mediated rapid C-[11C]methylation toward imaging DNA repair protein O6-methylguanine-DNA methyltransferase in glioblastoma
  作者：Hiroko Koyama、Hiroshi Ikenuma、Hiroshi Toda、Goro Kondo、Masaki Hirano、Masaya Kato、Junichiro Abe、Takashi Yamada、Toshihiko Wakabayashi、Kengo Ito、Atsushi Natsume、Masaaki Suzuki

  DOI：10.1016/j.bmcl.2017.03.045

  日期：2017.5

  majority of glioblastoma multiform. For clinical diagnosis, it is hoped that the MGMT expression level could be determined by a noninvasive method to understand the detailed biological properties of MGMT-specific tumors. We synthesized 11C-labeled O6-[(3-methyl)benzyl]guanine ([11C]mMeBG) as a positron emission tomography probe. Thus, a mixed amine-protected stannyl precursor, N9-(tert-butoxycarbonyl)-O6-

  O6-苄基鸟嘌呤（O6-BG）是O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的底物，在大多数胶质母细胞瘤形式中，它参与化学疗法的耐药性。对于临床诊断，希望可以通过非侵入性方法确定MGMT表达水平，以了解MGMT特异性肿瘤的详细生物学特性。我们合成了11C标记的O6-[（3-甲基）苄基]鸟嘌呤（[11C] mMeBG）作为正电子发射断层扫描探头。因此，在[11C]下将混合的胺保护的苯乙烯前体N9-（叔丁氧基羰基）-O6- [3-（三丁基锡烷基）苄基] -N2-（三氟乙酰基）鸟嘌呤进行快速C- [11C]甲基化。 NMP中的CH3I / [Pd2（dba）3] / P（o-CH3C6H4）3 / CuCl / K2CO3，然后用LiOH / H2O快速脱保护，得到[11C] mMeBG，总放射性为1。
• 11C -LABELED O6 -BENZYLGUANINE, PET PROBE CAPABLE OF VISUALIZING O6 -METHYL GUANINE METHYL-TRANSFERASE ACTIVITY, AND PRODUCTION METHOD OF THE SAME
  申请人：NATIONAL CENTER FOR GERIATRICS AND GERONTOLOGY

  公开号：US20190308974A1

  公开（公告）日：2019-10-10

  An object of the invention is to provide a 11 C-labeled O 6 -benzylguanine capable of obtaining a PET image and a process for producing the same. The 11 C-labeled O 6 -benzylguanine of the invention is represented by the following chemical formula (a). The 11 C-labeled O 6 -benzylguanine is produced by: a coupling step of cross-coupling a methyl iodide labeled with 11 C and the following organotin compound (b) (R 1 represents an alkyl group, and R 2 and R 3 represent a leaving group which can be eliminated with a base.) in the presence of a palladium complex, a phosphine ligand, and cuprous halide in an aprotic lactam; and a desorption step of desorbing the leaving groups R 2 and R 3 of the coupling product obtained by the coupling step with a base.

  该发明的目的是提供一种能够获得PET图像的11C标记的O6-苄基鸟嘌呤以及其生产方法。该发明的11C标记的O6-苄基鸟嘌呤由以下化学式(a)表示。该发明的11C标记的O6-苄基鸟嘌呤通过以下步骤生产：在无水环酰胺中，在钯配合物、膦配体和卤化亚铜的存在下，通过交叉偶联11C标记的碘甲烷和以下的有机锡化合物(b)（其中R1代表烷基，R2和R3代表能够通过碱消除的离开基团）进行偶联步骤；以及通过碱脱除偶联步骤获得的偶联产物的离开基团R2和R3的脱附步骤。
• 11C -labeled 06 -benzylguanine, pet probe capable of visualizing 06-methyl guanine methyl-transferase activity, and production method of the same
  申请人：NATIONAL CENTER FOR GERIATRICS AND GERONTOLOGY

  公开号：US10981913B2

  公开（公告）日：2021-04-20

  An object of the invention is to provide a 11C-labeled O6-benzylguanine capable of obtaining a PET image and a process for producing the same. The 11C-labeled O6-benzylguanine of the invention is represented by the following chemical formula (a). The 11C-labeled O6-benzylguanine is produced by: a coupling step of cross-coupling a methyl iodide labeled with 11C and the following organotin compound (b) (R1 represents an alkyl group, and R2 and R3 represent a leaving group which can be eliminated with a base) in the presence of a palladium complex, a phosphine ligand, and cuprous halide in an aprotic lactam; and a desorption step of desorbing the leaving groups R2 and R3 of the coupling product obtained by the coupling step with a base.

  本发明的目的是提供一种能够获得 PET 图像的 11C 标记 O6-苄基鸟嘌呤及其生产工艺。 本发明的 11C 标记 O6-苄基鸟嘌呤由以下化学式（a）表示。 11C 标记的 O6-苄基鸟嘌呤是通过以下方法制得的：在钯络合物、膦配体和卤化亚铜的存在下，在非沸腾内酰胺中，将标记有 11C 的甲基碘和下列有机锡化合物（b）（R1 代表烷基，R2 和 R3 代表可使用碱消除的离去基团）进行交叉偶联的偶联步骤；以及使用碱对偶联步骤得到的偶联产物的离去基团 R2 和 R3 进行解吸的解吸步骤。
• Substitution of Aminomethyl at the Meta-Position Enhances the Inactivation of <i>O</i>⁶-Alkylguanine-DNA Alkyltransferase by <i>O</i>⁶-Benzylguanine
  作者：Gary T. Pauly、Natalia A. Loktionova、Qingming Fang、Sai Lakshmana Vankayala、Wayne C. Guida、Anthony E. Pegg

  DOI：10.1021/jm800675p

  日期：2008.11.27

  O-6-Benzylguanine is an irreversible inactivator of O-6-alkylguanine-DNA alkyltransferase currently in clinical trials to overcome alkyltransferase-mediated resistance to certain cancer chemotherapeutic alkylating agents. In order to produce more soluble alkyltransferase inhibitors, we have synthesized three aminomethyl-substituted O-6-benzylguanines and the three methyl analogs and found that the substitution of aminomethyl at the meta-position greatly enhances inactivation of alkyltransferase, whereas para-substitution has little effect and ortho-substitution virtually eliminates activity. Molecular modeling of their interactions with alkyltransferase provided a molecular explanation for these results. The square of the correlation coefficient (R-2) obtained between E-model scores (obtained from GLIDE XP/QPLD docking calculations) vs log(ED50) values via a linear regression analysis was 0.96. The models indicate that the ortho-substitution causes a steric clash interfering with binding, whereas the meta-aminomethyl substitution allows an interaction of the amino group to generate an additional hydrogen bond with the protein.
• Probing the ATP Ribose-Binding Domain of Cyclin-Dependent Kinases 1 and 2 with <i>O</i>⁶-Substituted Guanine Derivatives
  作者：Ashleigh E. Gibson、Christine E. Arris、Johanne Bentley、F. Thomas Boyle、Nicola J. Curtin、Thomas G. Davies、Jane A. Endicott、Bernard T. Golding、Sharon Grant、Roger J. Griffin、Philip Jewsbury、Louise N. Johnson、Veronique Mesguiche、David R. Newell、Martin E. M. Noble、Julie A. Tucker、Hayley J. Whitfield

  DOI：10.1021/jm020056z

  日期：2002.8.1

  O-6-Substituted guanines are adenosine 5'-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B I and CDK2/cyclin A, the O-6 substituent occupying the kinase ribose binding site. Fifty-eight O-6-substituted guanines were prepared to probe the ribose pocket, and the structures of four representative compounds bound to monomeric CDK2 were determined by X-ray crystallography. Optimum binding occurs with a moderately sized aliphatic 06 substituent that packs tightly against the hydrophobic patch presented by the glycine loop, centered on Val18, an interaction promoted by the conformational restraints imposed in a cyclohexylmethyl or cyclohexenylmethyl ring. Structure-based design generated (R)-(2-amino-9H-purin-6-yloxymethyl)pyrrolidin-2-one (56), which reproduces the reported hydrogen bonds formed between ATP and Asp86 and Gln131 but failed to improve inhibitory potency. Thus, the parent compound O-6-cyclohexylmethylguanine (NU2058, 25) is the preferred starting point for exploring other areas of the kinase active site.