6-amino-2-(butyloxy)-9-(4-piperidinylmethyl)-7,9-dihydro-8H-purin-8-one hydrochloride | 1208365-56-3

• 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-2-(butyloxy)-9-(4-piperidinylmethyl)-7,9-dihydro-8H-purin-8-one hydrochloride
• 英文别名: 6-amino-2-butoxy-9-(piperidin-4-ylmethyl)-7H-purin-8-one;hydrochloride
• CAS: 1208365-56-3
• 化学式: C₁₅H₂₄N₆O₂*ClH
• 分子量: 356.856
• InChiKey: PANCBMFBNCXZAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  105
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-amino-2-(butyloxy)-9-(4-piperidinylmethyl)-7,9-dihydro-8H-purin-8-one hydrochloride 在 三甲基乙酰氯 吡啶 、 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 6-amino-2-butoxy-9-[N-(2-(1,2-dipalmitoyl-sn-glycero-3-phospho)ethyl)-4-piperidinylmethyl]-8-hydroxypurine
  参考文献：
  名称：

  [EN] LIPIDATED OXOADENINE DERIVATIVES
  [FR] DÉRIVÉS D'OXOADÉNINE LIPIDÉS

  摘要：

  包含氮杂环取代氧代腺嘌呤分子的新型脂质化氧代腺嘌呤，通过共价键连接到磷脂或膦脂的化合物被证明是干扰素-a和其他免疫刺激细胞因子的诱导剂。这些化合物可用作免疫刺激剂和辅助剂。

  公开号：

  WO2011017611A1
• 作为产物：
  描述：

  1-Boc-4-溴甲基哌啶 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.5h， 生成 6-amino-2-(butyloxy)-9-(4-piperidinylmethyl)-7,9-dihydro-8H-purin-8-one hydrochloride
  参考文献：
  名称：

  [EN] LIPIDATED OXOADENINE DERIVATIVES
  [FR] DÉRIVÉS D'OXOADÉNINE LIPIDÉS

  摘要：

  包含氮杂环取代氧代腺嘌呤分子的新型脂质化氧代腺嘌呤，通过共价键连接到磷脂或膦脂的化合物被证明是干扰素-a和其他免疫刺激细胞因子的诱导剂。这些化合物可用作免疫刺激剂和辅助剂。

  公开号：

  WO2011017611A1

文献信息

• [EN] ADENINE DERIVATIVES WHICH ARE USEFUL IN THE TREATMENT OF ALLERGIC DISEASES OR OTHER INFLAMMATORY CONDITIONS<br/>[FR] DÉRIVÉS D'ADÉNINE UTILES POUR TRAITER DES MALADIES ALLERGIQUES OU D'AUTRES PATHOLOGIES INFLAMMATOIRES
  申请人：GLAXOSMITHKLINE BIOLOG SA

  公开号：WO2016075661A1

  公开（公告）日：2016-05-19

  Compounds of formula (I).

  化合物的化学式（I）。
• [EN] NOVEL ADENINE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS D'ADÉNINE
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2010018134A1

  公开（公告）日：2010-02-18

  Compounds of formula (I) wherein R1 is C1-6alkylamino, or C1-6alkoxy; R2 is a group having the structure (II): n is an integer having a value of 1 to 6; Het is a 6-membered saturated heterocycle containing one nitrogen atom wherein Het is attached to the -(CH2)n- moiety at any carbon atom of the heterocycle; R3 is hydrogen, C1-8alkyl, or C3-7cycloalkylC0-6alkyl; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.

  式(I)的化合物中，其中R1是C1-6烷基氨基或C1-6烷氧基；R2是具有结构(II)的基团：n是一个值为1至6的整数；Het是一个含有一个氮原子的6元饱和杂环，其中Het连接到杂环的任何碳原子上的-(CH2)n-基团；R3是氢、C1-8烷基或C3-7环烷基C0-6烷基；以及其盐是人干扰素的诱导剂。诱导人干扰素的化合物可能在治疗各种疾病中有用，例如治疗过敏性疾病和其他炎症性疾病，例如过敏性鼻炎和哮喘，治疗传染性疾病和癌症，并且还可能作为疫苗佐剂有用。
• LIPIDATED OXOADENINE DERIVATIVES
  申请人：GlaxoSmithKline Biologicals S.A.

  公开号：EP3199159A1

  公开（公告）日：2017-08-02

  Novel lipidated oxoadenines comprising a nitrogen heterocyclyl-substituted oxoadenine molecule covalently linked to a phospho- or phosphonolipid are shown to be inducers of interferon-a and other immunostimulatory cytokines. The compounds are useful as immunostimulators and adjuvants.

  新型脂质化氧杂腺嘌呤包括一个与磷脂或磷脂共价连接的氮杂环取代氧杂腺嘌呤分子，已被证明是干扰素-a 和其他免疫刺激细胞因子的诱导剂。这些化合物可用作免疫刺激剂和佐剂。
• Optimization of 8-oxoadenines with toll-like-receptor 7 and 8 activity
  作者：Hélène G. Bazin、Laura S. Bess、Mark T. Livesay、Yufeng Li、Van Cybulski、Shannon M. Miller、David A. Johnson、Jay T. Evans

  DOI：10.1016/j.bmcl.2020.126984

  日期：2020.3

  Toll-like receptors 7 and 8 (TLR7/8) agonists are potent immunostimulants that are attracting considerable interest as vaccine adjuvants. We recently reported the synthesis of a new series of 2-O-butyl-8-oxoadenines substituted at the 9-position with various linkers and N-heterocycles, and showed that TLR7/8 selectivity, potency and cytokine induction could be modulated by varying the alkyl linker length and the N-heterocyclic ring. In the present study, we further optimized the oxoadenine scaffold by investigating the effect of different substituents at the 2-position of the oxoadenine on TLR7/8 potency/selectivity, cytokine induction and DC maturation in human PBMCs. The results show that introducing a 1-(S)-methylbutoxy group at the 2-position of the oxoadenine significantly increased potency for TLR7/8 activity, cytokine induction and DC maturation.
• Structural requirements for TLR7-selective signaling by 9-(4-piperidinylalkyl)-8-oxoadenine derivatives
  作者：Hélène G. Bazin、Yufeng Li、Juhienah K. Khalaf、Sandra Mwakwari、Mark T. Livesay、Jay T. Evans、David A. Johnson

  DOI：10.1016/j.bmcl.2015.01.037

  日期：2015.3

  We report the synthesis and biological evaluation of a new series of 8-oxoadenines substituted at the 9-position with a 4-piperidinylalkyl moiety. In vitro evaluation of the piperidinyl-substituted oxoadenines 3a-g in human TLR7- or TLR8-transfected HEK293 cells and in human PBMCs indicated that TLR7/8 selectivity/potency and cytokine induction can be modulated by varying the length of the alkyl linker. Oxoadenine 3f containing a 5-carbon linker was found to be the most potent TLR7 agonist and IFN alpha inducer in the series whereas 3b possessing a 1-carbon linker was the most potent TLR8 agonist. (C) 2015 Elsevier Ltd. All rights reserved.