2-butoxy-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine

• 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-butoxy-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine
• 英文别名: Methyl3-[(6-amino-2-butoxy-7,8-dihydro-8-oxo-9H-purin-9-yl)methyl]benzeneacetate；methyl 2-[3-[(6-amino-2-butoxy-8-oxo-7H-purin-9-yl)methyl]phenyl]acetate
• 化学式: C₁₉H₂₃N₅O₄
• 分子量: 385.423
• InChiKey: MXILFZWMVNDOIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-butoxy-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以96%的产率得到2-(3-{[6-amino-2-butoxy-8-oxo-7H-purin-9(8H)-yl]methyl}phenyl)acetic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 8-Oxoadenine Derivatives as Toll-like Receptor 7 Agonists Introducing the Antedrug Concept

  摘要：

  Systemic administration of a Toll-like receptor 7 (TLR7) agonist is effective to in suppressing Th2 derived inflammation, however systemic induction of various cytokines such as IL-6, IL-12, and type I interferon (IFN) is observed. This cytokine induction would be expected to cause flu-like symptoms. We have previously reported adenine compounds (3, 4) as interferon inducing agents acting as TLR7 agonists. To identify potent anti-inflammatory compounds without systemic side effects, a labile carboxylic ester as an antedrug functionality onto the N(9)-benzyl group of the adenine was introduced. We found that 9e was a potent TLR7 agonist (EC(50) 50 nM) and rapidly metabolized by human plasma (T(1/2)2.6 min) to the pharmacologically much less active carboxylic acid 16. Intratracheal administration of 9e effectively inhibited allergen-induced airway inflammation without inducing cytokines systemically. Therefore, the TLR7 agonist with antedrug characteristics 9e (SM-324405) is a novel candidate for immunotherapy of allergic diseases.

  DOI：

  10.1021/jm100070n
• 作为产物：
  描述：

  methyl {3-[(6-amino-8-bromo-2-butoxy-9H-purin-9-yl)methyl]phenyl}acetate 在 sodium hydroxide 、 硫酸 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以77%的产率得到2-butoxy-8-hydroxy-9-(3-methoxycarbonylmethylbenzyl)adenine
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 8-Oxoadenine Derivatives as Toll-like Receptor 7 Agonists Introducing the Antedrug Concept

  摘要：

  Systemic administration of a Toll-like receptor 7 (TLR7) agonist is effective to in suppressing Th2 derived inflammation, however systemic induction of various cytokines such as IL-6, IL-12, and type I interferon (IFN) is observed. This cytokine induction would be expected to cause flu-like symptoms. We have previously reported adenine compounds (3, 4) as interferon inducing agents acting as TLR7 agonists. To identify potent anti-inflammatory compounds without systemic side effects, a labile carboxylic ester as an antedrug functionality onto the N(9)-benzyl group of the adenine was introduced. We found that 9e was a potent TLR7 agonist (EC(50) 50 nM) and rapidly metabolized by human plasma (T(1/2)2.6 min) to the pharmacologically much less active carboxylic acid 16. Intratracheal administration of 9e effectively inhibited allergen-induced airway inflammation without inducing cytokines systemically. Therefore, the TLR7 agonist with antedrug characteristics 9e (SM-324405) is a novel candidate for immunotherapy of allergic diseases.

  DOI：

  10.1021/jm100070n

文献信息

• [EN] FUNCTIONAL LIPID DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS LIPIDIQUES FONCTIONNELS ET LEURS UTILISATIONS
  申请人：OHIO STATE INNOVATION FOUNDATION

  公开号：WO2021237055A1

  公开（公告）日：2021-11-25

  The present disclosure relates to compounds, compositions, and methods for delivery of therapeutic, diagnostic, or prophylactic agents (for example, a nucleic acid).

  本公开涉及化合物、组合物和用于传递治疗、诊断或预防性药剂（例如核酸）的方法。
• [EN] IMMUNOTHERAPEUTIC TUMOR TREATMENT METHOD<br/>[FR] MÉTHODE DE TRAITEMENT DE TUMEUR IMMUNOTHÉRAPEUTIQUE
  申请人：NEKTAR THERAPEUTICS

  公开号：WO2018204528A1

  公开（公告）日：2018-11-08

  Provided is a method of administering to a patient having cancer: (a) a 4-1BB agonist; (b) an IL-2Rβ-activating amount of a long-acting, IL-2Rβ-selective agonist; and/or (c) a toll-like receptor agonist, as well as related compositions, kits and compositions.

  提供一种治疗癌症患者的方法：(a) 4-1BB激动剂；(b)长效、选择性激活IL-2Rβ的激动剂的IL-2Rβ激活剂量；和/或(c)类似于toll样受体的激动剂，以及相关的组合物、套装和组合物。
• Novel adenine compound and use thereof
  申请人：Isobe Yoshiaki

  公开号：US20060052403A1

  公开（公告）日：2006-03-09

  A drug for topically administration which is effective as an antiallergic agent. The drug for topically administration contains as an active ingredient an adenine compound represented by the general formula (1): [wherein ring A represents a 6 to 10 membered, mono or bicyclic, aromatic hydrocarbon or a 5 to 10 membered, mono or bicyclic, aromatic heterocycle containing one to three heteroatoms selected among 0 to 2 nitrogen atoms, 0 or 1 oxygen atom, and 0 or 1 sulfur atom; n is an integer of 0 to 2; m is an integer of 0 to 2; R represents halogeno, (un)substituted alkyl, etc.; X 1 represents oxygen, sulfur, NR 1 (R 1 represents hydrogen or alkyl), or a single bond; Y 1 represents a single bond, alkylene, etc.; Y 2 represents a single bond, alkylene, etc.; Z represents alkylene; and at least one of Q 1 and Q 2 represents —COOR 10 (wherein R 10 represents (un)substituted alkyl, etc.), etc.] or a pharmaceutically acceptable salt of the compound.

  一种适用于局部给药的药物，作为抗过敏剂有效。该药物含有一种腺嘌呤化合物作为活性成分，该化合物由通式（1）表示：[其中环A表示6-10个成员、单环或双环、芳香烃或含有1-3个杂原子（选自0-2个氮原子、0或1个氧原子和0或1个硫原子）的5-10个成员、单环或双环、芳香杂环；n为0-2的整数；m为0-2的整数；R表示卤素、（未）取代的烷基等；X1表示氧、硫、NR1（R1表示氢或烷基）或单键；Y1表示单键、亚烷基等；Y2表示单键、亚烷基等；Z表示亚烷基；Q1和Q2中至少一个表示—COOR10（其中R10表示（未）取代的烷基等），等等]或该化合物的药学上可接受的盐。
• 8-Oxoadenine Compound
  申请人：Ogita Haruhisa

  公开号：US20070225303A1

  公开（公告）日：2007-09-27

  An 8-oxoadenine compound useful as an immuno-modulator having specific activity against Th1/Th2, specifically a prophylactic and therapeutic agent for a topical application for allergic diseases, viral diseases and cancers, which is represented by the following formula (1): wherein A is a group of a formula represented by the formula (2): wherein R 2 is a substituted or unsubstituted alkyl group and so on, R 3 is hydrogen atom or an alkyl group, R is a halogen atom and so on, n is 0˜2, X 1 is oxygen atom, Z is straight or branched chain alkylene, and R 1 is an alkyl group which is optionally substituted by hydroxy group, an alkoxy group, alkoxycarbonyl group and so on, or its pharmaceutically acceptable salt.

  一种8-氧腺嘌呤化合物，可用作免疫调节剂，对Th1 / Th2具有特定活性，特别是用于过敏性疾病，病毒性疾病和癌症的局部应用的预防和治疗剂，其化学式（1）如下：其中A是由式（2）表示的式的基团：其中R2是取代或未取代的烷基基团等，R3是氢原子或烷基基团，R是卤素原子等，n为0〜2，X1为氧原子，Z为直链或支链烷基，R1为烷基基团，可选地由羟基基团，烷氧基基团，烷氧羰基基团等取代，或其药学上可接受的盐。
• 9-Substituted 8-oxoadenine compound
  申请人：Kurimoto Ayumu

  公开号：US20070190071A1

  公开（公告）日：2007-08-16

  The present invention provides an 8-oxoadenine compound having immunemodulating activities such as an interferon inducing activity and useful as an antiviral agent and antiallergic agent, which is represented by the following formula (1): [wherein the ring A represents a 6-10 membered aromatic carbocyclic ring and the like, R represents a halogen atom, an alkyl group and the like, n represents an integer of 0-2, Z 1 represents alkylene, X 2 represents oxygen atom, sulfur atom, SO 2 , NR 5 , CO, CONR 5 , NR 5 CO and the like, Y 1 , Y 2 and Y 3 represent independently a single bond or an alkylene group, X 1 represents oxygen atom, sulfur atom, NR 4 (R 4 is hydrogen atom or an alkyl group) or a single bond, R 2 represents a substituted or unsubstituted alkyl group, R 1 represents hydrogen atom, hydroxy group, an alkoxy group, an alkoxycarbonyl group or a haloalkyl group] or its pharmaceutically acceptable salt.

  本发明提供了一种具有免疫调节活性的8-氧腺嘌呤化合物，例如干扰素诱导活性，并且可用作抗病毒剂和抗过敏剂，其化学式如下（1）所示：[其中，环A代表6-10个成员的芳香环烷基环等，R代表卤素原子，烷基等，n代表0-2的整数，Z1代表烷基，X2代表氧原子，硫原子，SO2，NR5，CO，CONR5，NR5CO等，Y1，Y2和Y3独立地代表单键或烷基，X1代表氧原子，硫原子，NR4（R4为氢原子或烷基）或单键，R2代表取代或未取代的烷基，R1代表氢原子，羟基，烷氧基，烷氧羰基或卤代烷基]或其药学上可接受的盐。