[5-(1,3-diallyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]acetic acid | 574005-50-8

• 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: [5-(1,3-diallyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]acetic acid
• 英文别名: 2-[5-(1,3-diallyl-xanthin-8-yl)-1-methyl-pyrazol-3-yl)oxyacetic acid；2-[5-[2,6-dioxo-1,3-bis(prop-2-enyl)-7H-purin-8-yl]-1-methylpyrazol-3-yl]oxyacetic acid
• CAS: 574005-50-8
• 化学式: C₁₇H₁₈N₆O₅
• 分子量: 386.367
• InChiKey: MKIOOTWHAUZAFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [5-(1,3-diallyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]acetic acid 在 palladium on activated charcoal 超重氢 、 1-羟基苯并三唑 、 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， 反应 4.0h， 生成 [3H]-MRE 2029F20
  参考文献：
  名称：

  [3H]-MRE 2029-F20, a selective antagonist radioligand for the human A2B adenosine receptors

  摘要：

  MRE 2029-F20 [N-benzo[1,3]dioxol-5-yl-2-[5-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]-acetamide] is a selective antagonist ligand of A(2B) adenosine receptors. For use as a radioligand, 1,3-diallyl-xanthine, the precursor of [H-3]-MRE 2029-F20, was synthesized, and tritiated on the allyl groups. [H-3]-MRE 2029-F20 bound to human A(2B) receptors expressed in CHO cells showed a K-D value of 1.65 +/- 0.10 nM and B-max value of 36 +/- 4 fmol/mg protein. [H-3]-MRE2029-F20 represents a useful tool for the pharmacological characterization of human A(2)B adenosine receptor subtype. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.084
• 作为产物：
  描述：

  1,3-二烯丙基-5,6-二氨基尿苷盐酸 在 sodium hydroxide 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 [5-(1,3-diallyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]acetic acid
  参考文献：
  名称：

  [3H]-MRE 2029-F20, a selective antagonist radioligand for the human A2B adenosine receptors

  摘要：

  MRE 2029-F20 [N-benzo[1,3]dioxol-5-yl-2-[5-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-1-methyl-1H-pyrazol-3-yloxy]-acetamide] is a selective antagonist ligand of A(2B) adenosine receptors. For use as a radioligand, 1,3-diallyl-xanthine, the precursor of [H-3]-MRE 2029-F20, was synthesized, and tritiated on the allyl groups. [H-3]-MRE 2029-F20 bound to human A(2B) receptors expressed in CHO cells showed a K-D value of 1.65 +/- 0.10 nM and B-max value of 36 +/- 4 fmol/mg protein. [H-3]-MRE2029-F20 represents a useful tool for the pharmacological characterization of human A(2)B adenosine receptor subtype. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.084

文献信息

• Design, Synthesis, and Biological Evaluation of New 8-Heterocyclic Xanthine Derivatives as Highly Potent and Selective Human A_2B Adenosine Receptor Antagonists
  作者：Pier Giovanni Baraldi、Mojgan Aghazadeh Tabrizi、Delia Preti、Andrea Bovero、Romeo Romagnoli、Francesca Fruttarolo、Naser Abdel Zaid、Allan R. Moorman、Katia Varani、Stefania Gessi、Stefania Merighi、Pier Andrea Borea

  DOI：10.1021/jm0309654

  日期：2004.3.1

  in radioligand binding assays at human (h) A(1), A(2A), A(2B), and A(3) ARs. We introduced several heterocycles, such as pyrazole, isoxazole, pyridine, and pyridazine, at the 8-position of the xanthine nucleus and we have also investigated different spacers (substituted acetamide, oxyacetamide, and urea moieties) on the heterocycle introduced. Various groups at the 3- and 4-positions of phenylacetamide

  在这里，我们报告8杂环取代的黄嘌呤作为有效和选择性A（2B）腺苷受体拮抗剂的合成。探索了黄嘌呤与重组人A（2B）腺苷受体（ARs）结合在HEK-293细胞（HEK-A（2B））和其他AR亚型中的结构活性关系（SAR）。合成的化合物在纳摩尔浓度范围内显示出A（2B）腺苷受体亲和力，并且在人类（h）A（1），A（2A），A（2B）和A（3）的放射性配体结合测定中评估了良好的选择性水平AR。我们在黄嘌呤核的8位引入了几个杂环，例如吡唑，异恶唑，吡啶和哒嗪，我们还研究了所引入杂环上的不同间隔基（取代的乙酰胺，氧乙酰胺和脲部分）。研究了苯基乙酰胺部分的3位和4位上的各种基团。这项研究使我们能够确定衍生物2-（3,4-二甲氧基苯基）-N- [5-（2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin- 8-基）-1-甲基-1H-吡唑-3-基]乙酰胺（29
• 8-Heteroaryl xanthine adenosine A2B receptor antagonists
  申请人：——

  公开号：US20030207879A1

  公开（公告）日：2003-11-06

  The present invention relates generally to compounds of formula (IA): (IA) 1 the preparation thereof, pharmaceutical formulations thereof, and their use in medicine as potent or selective A 2B adenosine receptor antagonists and their uses for treating asthma, autoimmune diseases and retinal vascular diseases.

  本发明总体上涉及公式（IA）的化合物：(IA)1，其制备方法、药物制剂及其在医学中的应用，作为强效或选择性的A2B腺苷受体拮抗剂，以及用于治疗哮喘、自身免疫疾病和视网膜血管疾病的用途。
• 8-heteroaryl xanthine adenosine A2B receptor antagonists
  申请人：King Pharmaceuticals Research and Development, Inc.

  公开号：US07335655B2

  公开（公告）日：2008-02-26

  The present invention relates generally to compounds of formula (I): wherein X is a five or six-membered heteroaromatic ring, containing one to four heteroatoms, selected from nitrogen, oxygen, or sulfur, provided that at least one heteroatom is nitrogen; and G1 and G2 are independently CH or N. The present invention also relates to the preparation of the compounds, pharmaceutical formulations thereof, and their use in medicine as potent or selective A2B adenosine receptor antagonists and their uses for treating asthma, autoimmune diseases and retinal vascular diseases.

  本发明涉及一般式（I）的化合物：其中X是一个含有一到四个杂原子的五元或六元杂芳环，所述杂原子选自氮、氧或硫，但至少有一个杂原子是氮；G1和G2是独立的CH或N。本发明还涉及该化合物的制备、药物配方以及其在医学上作为强效或选择性A2B腺苷受体拮抗剂的应用，以及其用于治疗哮喘、自身免疫性疾病和视网膜血管疾病的用途。
• 8-HETEROARYL XANTHINE ADENOSINE A SB 2B /SB RECEPTOR ANTAGONISTS
  申请人：King Pharmaceuticals Research and Development Inc.

  公开号：EP1469856A2

  公开（公告）日：2004-10-27
• EP1469856A4
  申请人：——

  公开号：EP1469856A4

  公开（公告）日：2005-06-22