5,6-diamino-1-benzyl-3-propyl-1H-pyrimidine-2,4-dione | 200557-55-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5,6-diamino-1-benzyl-3-propyl-1H-pyrimidine-2,4-dione
• 英文别名: 5,6-diamino-1-benzyl-3-propylpyrimidine-2,4(1H,3H)-dione；1-benzyl-3-propyl-5,6-diamino-uracil；5,6-diamino-1-benzyl-3-propylpyrimidine-2,4-dione
• CAS: 200557-55-7
• 化学式: C₁₄H₁₈N₄O₂
• 分子量: 274.323
• InChiKey: IKKRCMAXZREWHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-diamino-1-benzyl-3-propyl-1H-pyrimidine-2,4-dione 在 palladium on activated charcoal sodium hydroxide 、 ammonium formate 、 sodium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.75h， 生成 8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine
  参考文献：
  名称：

  A₁ Adenosine Receptor Antagonists as Ligands for Positron Emission Tomography (PET) and Single-Photon Emission Tomography (SPET)

  摘要：

  The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A(1) adenosine receptor (A(1)AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-ii, fluorine-18, or radioiodine will not alter affinity for the A(1)AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [H-3]CPX to the A(1)AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the K-i of antagonism was greater than or equal to 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A(1)AR.

  DOI：

  10.1021/jm9705465
• 作为产物：
  描述：

  6-amino-1-benzyl-5-nitroso-3-propylpyrimidine-2,4(1H,3H)-dione 在 ammonium hydroxide 、 sodium dithionite 作用下， 以 水 为溶剂， 以92%的产率得到5,6-diamino-1-benzyl-3-propyl-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  亚型选择性荧光拮抗剂在人类细胞中腺苷A 1受体研究中的开发与应用

  摘要：

  腺苷A 1受体（A 1 AR）是一种G蛋白偶联受体（GPCR），可为包括充血性心力衰竭，心动过速和神经性疼痛在内的多种疾病提供重要的治疗机会。A 1 AR选择性荧光配体的发展将增强我们对A 1 AR药理学基础的亚细胞机制的理解，从而促进更有效和选择性疗法的发展。在此，我们报告A 1系列小说的设计，合成和应用基于8功能化的双环[2.2.2]辛基黄嘌呤和3功能化的8（金刚烷-1-基）黄嘌呤支架的AR选择性荧光探针。这些荧光偶联物允许使用NanoBRET定量动力学和平衡配体结合参数，并通过共聚焦成像和全内反射荧光（TIRF）显微镜观察活细胞中特定受体的分布模式。这样，本文所述的新颖的A 1 AR-选择性荧光拮抗剂可以与一系列基于荧光的技术结合应用，以促进对活细胞中A 1 AR分子药理学和信号传导的理解。

  DOI：

  10.1021/acs.jmedchem.0c02067

文献信息

• Novel adenosine A3 receptor modulators
  申请人：Baraldi Giovanni Pier

  公开号：US20060178385A1

  公开（公告）日：2006-08-10

  A class of novel antagonists for the adenosine A 3 receptor are disclosed. These compounds are useful as therapeutic agents for a number of diseases and medical conditions that are mediated by the A 3 receptor. The compounds of this invention are also useful as diagnostic agents for the A 3 receptor.

  本发明揭示了一类新型的腺苷A3受体拮抗剂。这些化合物可用作治疗多种由A3受体介导的疾病和医疗状况的治疗剂。本发明的这些化合物还可用作A3受体的诊断试剂。
• Adenosine A3 receptor modulators
  申请人：King Pharmaceuticals Research and Development, Inc.

  公开号：US07435740B2

  公开（公告）日：2008-10-14

  A class of novel antagonists for the adenosine A3 receptor are disclosed. These compounds are useful as therapeutic agents for a number of diseases and medical conditions that are mediated by the A3 receptor. The compounds of this invention are also useful as diagnostic agents for the A3 receptor.

  本发明揭示了一类新型的腺苷A3受体拮抗剂。这些化合物可用作治疗许多由A3受体介导的疾病和医疗状况的治疗剂。本发明的化合物也可用作A3受体的诊断剂。
• ——
  作者：

  DOI：——

  日期：——
• New Pyrrolo[2,1-<i>f</i>]purine-2,4-dione and Imidazo[2,1-<i>f</i>]purine-2,4-dione Derivatives as Potent and Selective Human A₃ Adenosine Receptor Antagonists
  作者：Pier Giovanni Baraldi、Delia Preti、Mojgan Aghazadeh Tabrizi、Francesca Fruttarolo、Romeo Romagnoli、Naser Abdel Zaid、Allan R. Moorman、Stefania Merighi、Katia Varani、Pier Andrea Borea

  DOI：10.1021/jm058008c

  日期：2005.7.1

  Compounds presenting an additional fused ring on the xanthine nucleus have been reported to exhibit antagonistic activity with various levels of affinity and selectivity toward the four adenosine receptors subtypes A(1) A(2A), A(2B), and A(3). This paper reports synthesis and biological evaluation of new 1-benzyl-3-propyl-IH,6H-pyrrolo[2,1-f]purine-2,4-diones and 1-benzyl-3propyl- 1H,8H-imidazo [2, 1-f] purine-2,4-diones, among which we identified potent and selective A(3) adenosine receptors antagonists. In particular, 1-benzyl-7-methyl-3-propyl-IH,8H-imidazo[2,1-f]purine-2,4-dione (11e) shows a K-i (hA(3)) value from binding assay of 0.8 nM.
• US7435740B2
  申请人：——

  公开号：US7435740B2

  公开（公告）日：2008-10-14