N-(2-(2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy)-acetamido)ethyl)hept-6-ynamide | 1309666-81-6

• 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: N-(2-(2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy)-acetamido)ethyl)hept-6-ynamide
• CAS: 1309666-81-6
• 化学式: C₂₈H₃₆N₆O₅
• 分子量: 536.631
• InChiKey: HPTNINKAVJSSDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.18
• 重原子数：
  39.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  140.11
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  6-庚炔酸 、 3,7-二乙基-9-(4-(N-2-氨基乙基甲酰氨基甲氧基))苯基黄嘌呤 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以72%的产率得到N-(2-(2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenoxy)-acetamido)ethyl)hept-6-ynamide
  参考文献：
  名称：

  [EN] METHANOCARBA ADENOSINE DERIVATIVES AND DENDRIMER CONJUGATES THEREOF
  [FR] DÉRIVÉS DE MÉTHANOCARBA-ADÉNOSINE ET CONJUGUÉS DE DENDRIMÈRE DE CEUX-CI

  摘要：

  揭示了(N)-methanocarba腺嘌呤核苷，例如，化学式(I)所示的腺苷受体A3激动剂，包括这种核苷的药物组合物，以及这些核苷的使用方法，其中A、a、R2和R3如规范中定义。这些核苷被考虑用于治疗多种疾病，例如炎症、心脏缺血、中风、哮喘、糖尿病和心律失常。还揭示了包括树枝状聚合物和一个或多个配体的共轭物，这些配体是G蛋白偶联受体（GPCR）超家族受体的激动剂或拮抗剂的功能化同系物。这种共轭物有潜力用作双激动剂、双拮抗剂或激动剂/拮抗剂组合物。

  公开号：

  WO2011068978A1

文献信息

• GPCR Ligand Dendrimer (GLiDe) Conjugates: Adenosine Receptor Interactions of a Series of Multivalent Xanthine Antagonists
  作者：Angela Kecskés、Dilip K. Tosh、Qiang Wei、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1021/bc1005812

  日期：2011.6.15

  Previously, G protein-coupled receptor (GPCR) agonists were tethered from polyamidoamine (PAMAM) dendrimers to provide high receptor affinity and selectivity. Here, we prepared GPCR ligand-dendrimer (GLiDe) conjugates from a potent adenosine receptor (AR) antagonist; such agents are of interest for treating Parkinson's disease, asthma, and other conditions. Xanthine amine congener (XAC) was appended with an alkyne group on an extended C8 substituent for coupling by Cu(I)-catalyzed click chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. These conjugates also contained triazole-linked PEG groups (8 or 22 moieties per 64 terminal positions) for increasing water-solubility and optionally prosthetic groups for spectroscopic characterization and affinity labeling. Human AR binding affinity increased progressively with the degree of xanthine substitution to reach K-i values in the nanomolar range. The order of affinity of each conjugate was hA(2A)AR > hA(3)AR > hA(1)AR, while the corresponding monomer was ranked hA(2A)AR > hA(1)AR >= hA(3)AR. The antagonist activity of the most potent conjugate 14 (34 xanthines per dendrimer) was examined at the G(i)-coupled A(1)AR Conjugate 14 at 100 nM right-shifted the AR agonist concentration-response curve in a cyclic AMP functional assay in a parallel manner, but at 10 nM (lower than its K-i value), it significantly suppressed the maximal agonist effect in calcium mobilization. This is the first systematic probing of a potent AR antagonist tethered on a dendrinier and its activity as a function of variable loading.