9-benzyl-8-bromo-2-butoxy-9H-purine-6-amine | 226907-88-6

• 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-bromo-2-butoxy-9H-purine-6-amine
• 英文别名: 9-benzyl-8-bromo-2-butoxyadenine；6-Amino-9-benzyl-8-bromo-2-butoxypurine；9-benzyl-8-bromo-2-butoxypurin-6-amine
• CAS: 226907-88-6
• 化学式: C₁₆H₁₈BrN₅O
• 分子量: 376.256
• InChiKey: QCJNWNYJINQKLE-UHFFFAOYSA-N

物化性质

• 熔点：
  141-142 °C
• 沸点：
  584.8±60.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  78.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-benzyl-8-bromo-2-butoxy-9H-purine-6-amine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以94%的产率得到9-benzyl-2-n-butoxyadenine
  参考文献：
  名称：

  Synthesis and biological evaluation of 2,8-disubstituted 9-benzyladenines: discovery of 8-mercaptoadenines as potent interferon-inducers

  摘要：

  Recently, we have identified 9-benzyl-8-hydroxyadenines bearing an appropriate substituent (a butoxy, propylthio or butylamino group) at the 2-position as potent interferon (IFN)-inducers. Herein we report the design, synthesis, and IFN-inducing activity of 8-substituted 9-benzyladenines possessing such an appropriate substituent at the 2-position. Introduction of the appropriate substituent into the 2-position of the adenine nucleus gave rise to expression of the activity even in 9-benzyladenines bearing no hydroxyl group at the 8-position. An amino group at the 6-position and a hydroxyl or thiol group carrying an acidic proton at the 8-position are required to express excellent IFN-inducing activity. 9-Benzyl-2-butoxy-8-mercaptoadenine (9) indicated the most potent activity with MEC of 0.001 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00234-7
• 作为产物：
  描述：

  5-氨基-1-苄基-1H-咪唑-4-甲腈 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 97.17h， 生成 9-benzyl-8-bromo-2-butoxy-9H-purine-6-amine
  参考文献：
  名称：

  Efficient synthesis of 2,9-disubstituted 8-hydroxyadenine derivatives

  摘要：

  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。

  DOI：

  10.1039/b300557g

文献信息

• Facile syntheses of functionalized toll-like receptor 7 agonists
  作者：Babatope Akinbobuyi、Matthew R. Byrd、Charles A. Chang、Mysa Nguyen、Zacharie J. Seifert、Anne-Laure Flamar、Gerard Zurawski、Katherine C. Upchurch、SangKon Oh、Stephen H. Dempsey、Thomas J. Enke、John Le、Hunter J. Winstead、José R. Boquín、Robert R. Kane

  DOI：10.1016/j.tetlet.2014.11.126

  日期：2015.1

  Protein conjugates of toll-like receptor 7 agonists have been shown to elicit powerful immune responses. In order to facilitate our studies in this area our group has developed efficient syntheses for a number of functionalized derivatives that retain immune stimulatory activity.

  Toll样受体7激动剂的蛋白结合物已显示出引发强大的免疫反应。为了促进我们在这一领域的研究，我们小组已经开发出了许多保留免疫刺激活性的功能化衍生物的有效合成方法。
• 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 and immunostimulatory activity of substituted TLR7 agonists
  作者：Babatope Akinbobuyi、Lei Wang、Katherine C. Upchurch、Matthew R. Byrd、Charles A. Chang、Jeremy M. Quintana、Rachel E. Petersen、Zacharie J. Seifert、José R. Boquin、SangKon Oh、Robert R. Kane

  DOI：10.1016/j.bmcl.2016.07.049

  日期：2016.9

  Fifteen new substituted adenines were synthesized as potential TLR7 agonists. These compounds, along with 9 previously reported compounds, were analyzed for TLR7 activity and for the selective stimulation of B cell proliferation. Several functionalized derivatives exhibit significant activity, suggesting their potential for use as vaccine adjuvants.

  合成了十五种新的取代腺嘌呤作为潜在的TLR7激动剂。分析了这些化合物以及9种先前报道的化合物的TLR7活性和B细胞增殖的选择性刺激。几种功能化的衍生物表现出显着的活性，表明它们可用作疫苗佐剂的潜力。
• 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。
• Substituted purine derivative
  申请人：SUMITOMO DAINIPPON PHARMA CO., LTD.

  公开号：US10703755B2

  公开（公告）日：2020-07-07

  The present invention relates to a substituted purine derivative of formula (1) wherein R1 is alkoxy or the like, R2 is alkyl or the like, Ring Q1 is aryl or the like, W1 is alkylene or the like, Ring Q2 is aromatic carbocyclyl or the like, n is 1-4, R3 is hydrogen atom or the like, X1 is single bond or the like, W2 is alkylene or the like, and R4 is hydrogen atom or the like, or a pharmaceutically acceptable salt thereof, which has a potent inhibitory effect against TLR7, and thereby is useful for treating autoimmune disease.

  本发明涉及式(1)的取代嘌呤衍生物，其中R1是烷氧基或类似物，R2是烷基或类似物，环Q1是芳基或类似物，W1是亚烷基或类似物，环Q2是芳香族羰基或类似物，n是1-4、R3 是氢原子或类似物，X1 是单键或类似物，W2 是亚烷基或类似物，R4 是氢原子或类似物，或其药学上可接受的盐，对 TLR7 具有强效抑制作用，因此可用于治疗自身免疫性疾病。