2-(2-furyl)-5-methylthio-7-n-pentylcarbonylamino-[1,2,4]-triazolo[1,5-a]-[1,3,5]triazine | 1227270-11-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(2-furyl)-5-methylthio-7-n-pentylcarbonylamino-[1,2,4]-triazolo[1,5-a]-[1,3,5]triazine
• 英文别名: N-[2-(furan-2-yl)-5-methylsulfanyl-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-yl]hexanamide
• CAS: 1227270-11-2
• 化学式: C₁₅H₁₈N₆O₂S
• 分子量: 346.413
• InChiKey: HWWAJIDHSOUPND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  己酰氯 、 [1,2,4]三唑并[1,5-a][1,3,5]三嗪-7-胺,2-(2-呋喃基)-5-(甲硫基)- 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以70%的产率得到2-(2-furyl)-5-methylthio-7-n-pentylcarbonylamino-[1,2,4]-triazolo[1,5-a]-[1,3,5]triazine
  参考文献：
  名称：

  Synthesis and pharmacological characterization of a new series of 5,7-disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives as adenosine receptor antagonists: A preliminary inspection of ligand–receptor recognition process

  摘要：

  A new series of triazolotriazines variously substituted at the C5 and N7 (5-25) positions was synthesized and fully characterized at the four adenosine receptor (AR) subtypes. In particular, arylacetyl or arylcarbamoyl moieties were introduced at the N7 position, which enhanced affinity at the hA(2B) and hA(3) ARs, respectively, when utilized on the pyrazolo-triazolopyrimidine nucleus as we reported in the past. In general, compounds with a free amino group at the 7 position (5, 6), showed good affinity at the rat (r) A(2A) AR (range 18.3-96.5 nM), while the introduction of a phenylcarbamoyl moiety at the N7 position (12, 19, 24) slightly increased the affinity at the hA3 AR (range 311-633 nM) with respect to the unsubstituted derivatives. The binding profiles of the synthesized analogues seemed to correlate with the substitutions at the C5 and N7 positions. At the hA2B AR, derivative 5, which contained a free amino group at the 7 position, was the most potent (EC50 3.42 mu M) and could represent a starting point for searching new non-xanthine hA2B AR antagonists. Molecular models of the rA(2A) and hA3 ARs were constructed by homology to the recently reported crystallographic structure of the hA(2A) AR. A preliminary receptor-driven structure-activity relationship (SAR) based on the analysis of antagonist docking has been provided. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.02.039

文献信息

• Synthesis and pharmacological characterization of a new series of 5,7-disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives as adenosine receptor antagonists: A preliminary inspection of ligand–receptor recognition process
  作者：Giorgia Pastorin、Stephanie Federico、Silvia Paoletta、Marta Corradino、Francesca Cateni、Barbara Cacciari、Karl-Norbert Klotz、Zhan-Guo Gao、Kenneth A. Jacobson、Giampiero Spalluto、Stefano Moro

  DOI：10.1016/j.bmc.2010.02.039

  日期：2010.4

  A new series of triazolotriazines variously substituted at the C5 and N7 (5-25) positions was synthesized and fully characterized at the four adenosine receptor (AR) subtypes. In particular, arylacetyl or arylcarbamoyl moieties were introduced at the N7 position, which enhanced affinity at the hA(2B) and hA(3) ARs, respectively, when utilized on the pyrazolo-triazolopyrimidine nucleus as we reported in the past. In general, compounds with a free amino group at the 7 position (5, 6), showed good affinity at the rat (r) A(2A) AR (range 18.3-96.5 nM), while the introduction of a phenylcarbamoyl moiety at the N7 position (12, 19, 24) slightly increased the affinity at the hA3 AR (range 311-633 nM) with respect to the unsubstituted derivatives. The binding profiles of the synthesized analogues seemed to correlate with the substitutions at the C5 and N7 positions. At the hA2B AR, derivative 5, which contained a free amino group at the 7 position, was the most potent (EC50 3.42 mu M) and could represent a starting point for searching new non-xanthine hA2B AR antagonists. Molecular models of the rA(2A) and hA3 ARs were constructed by homology to the recently reported crystallographic structure of the hA(2A) AR. A preliminary receptor-driven structure-activity relationship (SAR) based on the analysis of antagonist docking has been provided. (C) 2010 Elsevier Ltd. All rights reserved.