2,6-diamino-9-benzylpurine | 7674-36-4

• 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: 2,6-diamino-9-benzylpurine
• 英文别名: 9-Benzylpurine-2,6-diamine；2-amino-9-benzyladenine；9-benzyl-9H-purine-2,6-diamine；9-(phenylmethyl)-9H-purine-2,6-diamine；2,6-Diamino-9-benzylpurin
• CAS: 7674-36-4
• 化学式: C₁₂H₁₂N₆
• 分子量: 240.267
• InChiKey: DRGHOMRXJSSSBT-UHFFFAOYSA-N

物化性质

• 熔点：
  >300 °C
• 沸点：
  596.5±60.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  95.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,6-diamino-9-benzylpurine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 以17 %的产率得到2-amino-9-benzyl-8-bromoadenine
  参考文献：
  名称：

  腺嘌呤衍生物作为酪蛋白激酶 CK1delta 酶的抑制剂

  摘要：

  CK1δ 的过度表达与癌症和神经退行性疾病的发展有关，使得该蛋白的配体非常有希望用于治疗这些疾病的候选药物和/或用于其研究的药理学工具。对内部腺嘌呤衍生物库的筛选活动表明，一些化合物能够抑制 CK1δ 酶亚型，IC 50在低 µM 范围内。对酶的 X 射线结构进行分子对接分析，从而合理设计合成和表征的新型二取代和三取代腺嘌呤。生物学评价表明，新化合物具有中等的CK1δ抑制活性。特别是，在 40 µM 浓度下测试的2-氨基-9-苄基腺嘌呤 ( 12 ) 及其 8-溴衍生物14抑制酶，分别留下约 35% 和 42% 的残余活性。对接研究提供了对这些数据的解释，并为进一步开发这些化合物以获得更有效的 CK1δ 抑制剂提供了建议。

  DOI：

  10.1007/s00044-024-03202-6
• 作为产物：
  描述：

  2-氯-6-氨基嘌呤 在 氨 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2,6-diamino-9-benzylpurine
  参考文献：
  名称：

  Synthesis and structure–Activity relationships of 2-Amino-8-hydroxyadenines as orally active interferon inducing agents

  摘要：

  Recently, we have reported the 8-hydroxyadenine derivatives (2-4) as a novel class of interferon (IFN) inducing agents. In the present study, a series of 8-hydroxyadenines, which possess various amino moieties at the adenine C(2)-position, were synthesized and evaluated for their ability to induce endogenous IFN in comparison to the known active agent, Imiquimod. Among the compounds prepared, compound 9o possessing a 2-methoxyethylamino group at C(2)-position of adenine was found to exhibit potent IFN inducing activity in vivo. Compound 9o induced IFN from the dosage of 0.1 mg/kg, which was 30-fold potent than that of Imiquimod, and showed a good oral bioavailability (F = 81%) (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.09.032

文献信息

• Modulators of toll-like receptor 7
  申请人：Chong S. Lee

  公开号：US20080008682A1

  公开（公告）日：2008-01-10

  The present application provides for a compound of Formula I or II: or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods that include the administration of such compounds with at least one additional active agent.

  本申请提供了一种公式I或II的化合物： 或其药用可接受的盐、溶剂化物和/或酯，包含此类化合物的组合物，包括施用此类化合物的治疗方法和包括与至少一个附加活性剂施用此类化合物的治疗方法。
• Heterocyclic compounds
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：US06329381B1

  公开（公告）日：2001-12-11

  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。
• 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。
• Nucleic Acid Related Compounds. 136. Synthesis of 2-Amino- and 2,6-Diaminopurine Derivatives via Inverse-Electron-Demand Diels-Alder Reactions
  作者：Xiaoyu Lin、Morris J. Robins

  DOI：10.1135/cccc20061029

  日期：——

  Thermal inverse-electron-demand Diels-Alder reactions of 5-aminoimidazoles and 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine (2) with spontaneous retro-Diels-Alder loss of ethyl cyanoformate and elimination of ammonia give 2,6-bis(ethoxycarbonyl)purines. A report that selective alkaline hydrolysis followed by acid-catalyzed decarboxylation gave 6-(ethoxycarbonyl)purine products was not in harmony with known reactions in purine chemistry. Our reinvestigation has shown that the 6-(ethoxycarbonyl) group undergoes preferential base-promoted hydrolysis, as expected, but regioselectivity for attack of hydroxide at the carbonyl group at C6 is not high (relative to hydrolysis of both C2 and C6 esters). The structure of 9-benzyl-2-(ethoxycarbonyl)purine was determined by X-ray crystallography and confirmed by Curtius rearrangement of the azidocarbonyl analogue to give 2-amino-6-benzylpurine. Acid-catalyzed decarboxylation of the 2,6-dicarboxylate formed during hydrolysis gave 9-benzylpurine, and Curtius rearrangement of 2,6-bis(azidocarbonyl)-9-benzylpurine gave 2,6-diamino-9-benzylpurine. Attempted applications of inverse-electron-demand Diels-Alder reactions of 2 with nucleoside derivatives were problematic.

  5-氨基咪唑和2,4,6-三(乙氧羰基)-1,3,5-三嗪的热反向电子需求Diels-Alder反应与乙基氰甲酸乙酯自发性逆Diels-Alder失去和氨的消除反应，形成2,6-双(乙氧羰基)嘌呤。一份报告指出，选择性碱水解后接酸催化脱羧可得到6-(乙氧羰基)嘌呤产物，但与嘌呤化学中已知的反应不一致。我们的再研究表明，6-(乙氧羰基)基团更倾向于碱促水解，但羟基攻击C6羰基的区域选择性并不高（相对于C2和C6酯的水解）。9-苄基-2-(乙氧羰基)嘌呤的结构经X射线晶体学确定，并通过Curtius重排验证了其氮氧羰基类似物的2-氨基-6-苄基嘌呤。在水解过程中形成的2,6-二羧酸酯的酸催化脱羧产生了9-苄基嘌呤，而2,6-双(氮氧羰基)-9-苄基嘌呤的Curtius重排产生了2,6-二氨基-9-苄基嘌呤。尝试使用反向电子需求Diels-Alder反应与核苷衍生物的2进行应用时出现问题。
• [EN] PROCESS FOR THE PREPARATION OF 2-FLUOROADENINE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 2-FLUOROADÉNINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2020263660A1

  公开（公告）日：2020-12-30

  The present invention provides processes for the preparation of 2-fluoroadenine, as well as certain intermediates useful in the preparation of 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine (EFdA): EFdA.

  本发明提供了制备2-氟腺嘌呤的方法，以及制备2'-去氧-4'-C-乙炔基-2-氟腺苷（EFdA）所需的某些中间体：EFdA。

表征谱图