6-Amino-9-benzyl-2-(2-hydroxyethoxy)-9H-purin-6-amine | 226908-63-0

• 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: 6-Amino-9-benzyl-2-(2-hydroxyethoxy)-9H-purin-6-amine
• 英文别名: 6-Amino-9-benzyl-2-(2-hydroxyethoxy)purine；2-(6-amino-9-benzylpurin-2-yl)oxyethanol
• CAS: 226908-63-0
• 化学式: C₁₄H₁₅N₅O₂
• 分子量: 285.305
• InChiKey: CSFHWRGFZLDTMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  99.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-Amino-9-benzyl-2-(2-hydroxyethoxy)-9H-purin-6-amine 在 盐酸 、 溴 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 6-Amino-9-benzyl-8-hydroxy-2-(2-hydroxyethoxy)purine
  参考文献：
  名称：

  Synthesis and evaluation of 2-substituted 8-hydroxyadenines as potent interferon inducers with improved oral bioavailabilities

  摘要：

  In order to create novel compounds which possess potent interferon (IFN) inducing activities with excellent oral bioavailabilities, a series of 8-hydroxyadenines, which have various alkoxy or alkylthio moieties at the adenine C(2)-position, were synthesized and evaluated. The introduction of hydrophobic groups was not considered to be effective for potentiating the IFN-inducing activity, but several compounds having hydrophilic groups were effective. Among the compounds tested, compound 13f induced IFN from the dosage of 0.03 mg/kg, which was approximately 100-fold more potent than that of Imiquimod, and showed an excellent oral bioavailability (F = 40%) which was 10-fold improved over 5, a lead compound (F = 4%). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.12.008
• 作为产物：
  描述：

  9-苄基-2-氯腺嘌呤 在 sodium 作用下， 以 水 、 乙二醇 为溶剂， 以70%的产率得到6-Amino-9-benzyl-2-(2-hydroxyethoxy)-9H-purin-6-amine
  参考文献：
  名称：

  Heterocyclic compounds

  摘要：

  本发明涉及以下通式（I）的杂环化合物：其中X是硫原子、氧原子或—NR3—（R3可能通过氮原子与R1形成杂环环或取代杂环环），R1是烷基、取代烷基、芳基、取代芳基、杂环基或取代杂环基，R2是氢原子、卤原子等；或其药学上可接受的盐和干扰素诱导剂、抗病毒剂、抗癌剂和免疫性疾病治疗剂，包括化合物（I）或其药学上可接受的盐作为活性成分。

  公开号：

  US06329381B1

文献信息

• Synthesis of Acyclic Nucleotide Analogues Derived from N3-Substituted Isoguanine
  作者：Petr Alexander、Antonín Holý、Miloš Buděšínský、Milena Masojídková

  DOI：10.1135/cccc20001713

  日期：——

  Reaction of 9-benzyl-6-[(dimethylamino)methylidene]amino}purin-2(3H)-one (7) with ethylene carbonate gave a mixture of 9-benzyl-2-(2-hydroxyethoxy)purin-6-amine (10) and 2-amino-9-benzyl-3-(2-hydroxyethyl)purin-2(3H)-one (11). This mixture reacted with diisopropyl (tosyloxymethyl)phosphonate in the presence of NaH followed by catalytic hydrogenation and bromotrimethylsilane treatment to afford isomeric 6-amino-3-[2-(phosphonomethoxy)ethyl]purin-2(3H)-one (3) and 2-[2-(phosphonomethoxy)ethoxy]purin- 6-amine (15). Similar treatment of compound7with tritylglycidol gave two isomeric 2-hydroxy-3-(trityloxy)propyl derivatives18,20which were subsequently condensed with diisopropyl (tosyloxymethyl)phosphonate to afford protected diester intermediates21and22; these compounds were transformed by hydrogenolysis and ester cleavage with bromotrimethylsilane to the isomeric 6-amino-3-[3-hydroxy-2-(phosphonomethoxy)propyl]- purin-2(3H)-one (2) and 2-[3-hydroxy-2-(phosphonomethoxy)propoxy]purin-6-amine (24). None of the free phosphonates2,3,15or24exhibited any antiviral or cytostatic activity.

  9-苄基-6-[(二甲基氨基)甲基亚胺]氨基}嘌呤-2(3H)-酮 (7) 与碳酸乙烯酯反应生成了9-苄基-2-(2-羟基乙氧基)嘌呤-6-胺 (10) 和 2-氨基-9-苄基-3-(2-羟乙基)嘌呤-2(3H)-酮 (11) 的混合物。这个混合物在NaH存在下与异丙基(对甲苯磺酰氧甲基)磷酸二异丙酯反应，随后进行催化氢化和溴三甲基硅烷处理，得到异构体的6-氨基-3-[2-(磷酸甲氧基)乙基]嘌呤-2(3H)-酮 (3) 和 2-[2-(磷酸甲氧基)乙氧基]嘌呤-6-胺 (15)。对化合物7 进行类似处理，与三苯甲氧基环氧丙醇反应得到两种异构体的2-羟基-3-(三苯甲氧基)丙基衍生物18、20，随后与异丙基(对甲苯磺酰氧甲基)磷酸二异丙酯缩合形成保护二酯中间体21和22；这些化合物经过氢解和溴三甲基硅烷酯酯解反应转化为异构体的6-氨基-3-[3-羟基-2-(磷酸甲氧基)丙基]-嘌呤-2(3H)-酮 (2) 和 2-[3-羟基-2-(磷酸甲氧基)丙氧基]嘌呤-6-胺 (24)。任何自由磷酸酯2、3、15或24都没有表现出任何抗病毒或抗细胞增殖活性。
• NOVEL HETEROCYCLIC COMPOUNDS
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：EP1035123A1

  公开（公告）日：2000-09-13

  The present invention relates to a heterocyclic compound of the following general formula (I): wherein X is sulfur atom, oxygen atom or -NR3- (R3 may form a heterocyclic ring or a substituted heterocyclic ring with R1 via the nitrogen atom), R1 is alkyl group, substituted alkyl group, aryl group, substituted aryl group, heterocyclic group or substituted heterocyclic group, and R2 is hydrogen atom, halogen atom etc.; or its pharmaceutically acceptable salt and interferon inducers, antiviral agents, anticancer agents and therapeutic agents for immunologic diseases comprising the compound (I) or its pharmaceutically acceptable salt as active ingredients.

  本发明涉及以下通式(I)的杂环化合物： 其中 X 是硫原子、氧原子或-NR3-（R3 可通过氮原子与 R1 形成杂环或取代的杂环）、 R1 是烷基、取代的烷基、芳基、取代的芳基、杂环基或取代的杂环基，以及 R2 是氢原子、卤素原子等； 或其药学上可接受的盐，以及干扰素诱导剂、抗病毒剂、抗癌剂和以化合物（I）或其药学上可接受的盐为活性成分的免疫疾病治疗剂。
• US6329381B1
  申请人：——

  公开号：US6329381B1

  公开（公告）日：2001-12-11