9-benzyl-8-hydroxy-2-pentylaminoadenine

• 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: 9-benzyl-8-hydroxy-2-pentylaminoadenine
• 英文别名: 6-Amino-9-benzyl-8-hydroxy-2-pentylaminopurine；6-amino-9-benzyl-2-(pentylamino)-7H-purin-8-one
• 化学式: C₁₇H₂₂N₆O
• 分子量: 326.401
• InChiKey: QMNJVFQVFJJJDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氯-6-氨基嘌呤 在 盐酸 、 溴 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 9-benzyl-8-hydroxy-2-pentylaminoadenine
  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

• 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。
• Efficient synthesis of 2,9-disubstituted 8-hydroxyadenine derivatives
  作者：Kosaku Hirota、Kazunori Kazaoka、Itaru Niimoto、Hironao Sajiki

  DOI：10.1039/b300557g

  日期：2003.4.14

  An efficient and general method for the synthesis of 2,9-disubstituted 8-hydroxyadenines, which are expected to have various biological activities, was realized. 5-Amino-4-cyano-2-hydroxyimidazoles (1) were prepared from aminomalononitrile and isocyanates as key intermediates. The condensation of 1a with amidines, imidates, guanidine, urea and thioureas afforded 8-hydroxyadenines (2–6) possessing various substituents at the 2-position. Furthermore, selective alkylation of 2-amino- and 2-hydroxyadenines (4 and 6) successively proceeded to give the corresponding 2-alkylamino- and 2-alkoxyadenines (5 and 7), respectively. 2-Alkylthioadenines (15) were prepared by an analogous reaction of 1a with benzoyl isothiocyanate and subsequent S-alkylation. The imidazoles 1 are most useful intermediates for the synthesis of 8-hydroxyadenine derivatives.

  一种高效且通用的方法被实现，用于合成预期具有多种生物活性的2,9-二取代的8-羟基腺苷。5-氨基-4-氰基-2-羟基咪唑（1）是从氨基丙腈和异氰酸酯作为关键中间体制备的。将1a与氨基脲、咪唑、胍、尿素和硫脲缩合，得到在2位具有各种取代基的8-羟基腺苷（2–6）。此外，对2-氨基和2-羟基腺苷（4和6）进行选择性烷基化，顺利实现，分别得到相应的2-烷基氨基和2-烷氧腺苷（5和7）。2-烷基硫腺苷（15）是通过1a与苯甲酰异硫氰酸酯的类似反应以及随后S-烷基化制备的。咪唑类化合物1是合成8-羟基腺苷衍生物最有用的中间体。
• 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。
• Discovery of 8-Hydroxyadenines as a Novel Type of Interferon Inducer
  作者：Kosaku Hirota、Kazunori Kazaoka、Itaru Niimoto、Hiroshi Kumihara、Hironao Sajiki、Yoshiaki Isobe、Haruo Takaku、Masanori Tobe、Haruhisa Ogita、Tetsuhiro Ogino、Shinji Ichii、Ayumu Kurimoto、Hajime Kawakami

  DOI：10.1021/jm0203581

  日期：2002.12.1

  9-Benzyl-8-hydroxyadenine (6) was found to possess interferon-inducing activity in vitro as a lead compound. Although replacement of the 9-benzyl group of 6 did not improve the activity, the introduction of a substituent such as alkyl, alkylthio, alkylamino, and alkoxy groups into the 2-position of the adenine ring resulted in a remarkable increase in the activity. The 2-alkylthio (30-32), 2-butylamino (41), and 2-butoxy (47) analogues indicated the highest activities by oral administration to mice.
• US6329381B1
  申请人：——

  公开号：US6329381B1

  公开（公告）日：2001-12-11