O6-[4-(aminomethyl)benzyl]guanine hydrochloride | 948903-68-2

• 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-(aminomethyl)benzyl]guanine hydrochloride
• 英文别名: 6-((4-(Aminomethyl)benzyl)oxy)-7H-purin-2-amine hydrochloride；6-[[4-(aminomethyl)phenyl]methoxy]-7H-purin-2-amine;hydrochloride
• CAS: 948903-68-2
• 化学式: C₁₃H₁₄N₆O*ClH
• 分子量: 306.755
• InChiKey: WVICZTNHHXZQRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.39
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-((4-(氨基甲基)苄基)氧基)-7H-嘌呤-2-胺 在 盐酸 作用下， 以 水 为溶剂， 生成 O6-[4-(aminomethyl)benzyl]guanine hydrochloride
  参考文献：
  名称：

  Substitution of Aminomethyl at the Meta-Position Enhances the Inactivation of O⁶-Alkylguanine-DNA Alkyltransferase by O⁶-Benzylguanine

  摘要：

  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.

  DOI：

  10.1021/jm800675p