5-((2-(2-(4-(3-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)propyl)phenoxy)acetamido)ethyl)carbamoyl)-2-(6-(dimethylamino)-3-(dimethylimino)-3Hxanthen-9-yl)benzoate | 1309806-55-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 5-((2-(2-(4-(3-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)propyl)phenoxy)acetamido)ethyl)carbamoyl)-2-(6-(dimethylamino)-3-(dimethylimino)-3Hxanthen-9-yl)benzoate
• 英文别名: 5-[2-[[2-[4-[3-[7-Amino-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-10-yl]propyl]phenoxy]acetyl]amino]ethylcarbamoyl]-2-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoate
• CAS: 1309806-55-0
• 化学式: C₄₈H₄₅N₁₁O₇
• 分子量: 887.955
• InChiKey: UKMXRDZZVDKYFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  66
• 可旋转键数：
  14
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  223
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  4-(3-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)propyl)phenol 在 Sodium tetraborate decahydrate 、 caesium carbonate 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 5-((2-(2-(4-(3-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)propyl)phenoxy)acetamido)ethyl)carbamoyl)-2-(6-(dimethylamino)-3-(dimethylimino)-3Hxanthen-9-yl)benzoate
  参考文献：
  名称：

  Molecular probes for the A2A adenosine receptor based on a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold

  摘要：

  Pyrazolo[4,3-e][1,2,4] triazolo[1,5-c]pyrimidin-5-amine derivatives such as SCH 442416 display high affinity and selectivity as antagonists for the human A(2A) adenosine receptor (AR). We extended ether-linked chain substituents at the p-position of the phenyl group using optimized O-alkylation. The conjugates included an ester, carboxylic acid and amines (for amide condensation), an alkyne (for click chemistry), a fluoropropyl group (for F-18 incorporation), and fluorophore reporter groups (e. g., BODIPY conjugate 14, K-i 15 nM). The potent and A(2A)AR-selective N-aminoethylacetamide 7 and N-[2-(2-aminoethyl)-aminoethyl]acetamide 8 congeners were coupled to polyamidoamine (PAMAM) G3.5 dendrimers, and the multivalent conjugates displayed high A(2A)AR affinity. Theoretical docking of an AlexaFluor conjugate to the receptor X-ray structure highlighted the key interactions between the heterocyclic core and the binding pocket of the A(2A)AR as well as the distal anchoring of the fluorophore. In conclusion, we have synthesized a family of high affinity functionalized congeners as pharmacological probes for studying the A(2A)AR. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.11.082

文献信息

• Molecular probes for the A2A adenosine receptor based on a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold
  作者：T. Santhosh Kumar、Shilpi Mishra、Francesca Deflorian、Lena S. Yoo、Khai Phan、Miklos Kecskés、Angela Szabo、Bidhan Shinkre、Zhan-Guo Gao、William Trenkle、Kenneth A. Jacobson

  DOI：10.1016/j.bmcl.2010.11.082

  日期：2011.5

  Pyrazolo[4,3-e][1,2,4] triazolo[1,5-c]pyrimidin-5-amine derivatives such as SCH 442416 display high affinity and selectivity as antagonists for the human A(2A) adenosine receptor (AR). We extended ether-linked chain substituents at the p-position of the phenyl group using optimized O-alkylation. The conjugates included an ester, carboxylic acid and amines (for amide condensation), an alkyne (for click chemistry), a fluoropropyl group (for F-18 incorporation), and fluorophore reporter groups (e. g., BODIPY conjugate 14, K-i 15 nM). The potent and A(2A)AR-selective N-aminoethylacetamide 7 and N-[2-(2-aminoethyl)-aminoethyl]acetamide 8 congeners were coupled to polyamidoamine (PAMAM) G3.5 dendrimers, and the multivalent conjugates displayed high A(2A)AR affinity. Theoretical docking of an AlexaFluor conjugate to the receptor X-ray structure highlighted the key interactions between the heterocyclic core and the binding pocket of the A(2A)AR as well as the distal anchoring of the fluorophore. In conclusion, we have synthesized a family of high affinity functionalized congeners as pharmacological probes for studying the A(2A)AR. Published by Elsevier Ltd.