ethyl 5-amino-4-oxo-3-(4-(trifluoromethylsulfonyloxy)phenyl)-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate | 1062292-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩哒嗪类
• 英文名称: ethyl 5-amino-4-oxo-3-(4-(trifluoromethylsulfonyloxy)phenyl)-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate
• 英文别名: Ethyl 5-amino-4-oxo-3-(4-(trifluoromethylsulfonyloxy)phenyl)-3,4-dihydro-thieno[3,4-d]pyridazine-1-carboxylate；ethyl 5-amino-4-oxo-3-[4-(trifluoromethylsulfonyloxy)phenyl]thieno[3,4-d]pyridazine-1-carboxylate
• CAS: 1062292-71-0
• 化学式: C₁₆H₁₂F₃N₃O₆S₂
• 分子量: 463.415
• InChiKey: OBLPMIOAEQMPMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  165
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  N-苯基双(三氟甲烷磺酰)亚胺 、 ethyl 5-amino-3-(4-hydroxyphenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 在 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 0.1h， 以100%的产率得到ethyl 5-amino-4-oxo-3-(4-(trifluoromethylsulfonyloxy)phenyl)-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate
  参考文献：
  名称：

  2-Aminothienopyridazines as Novel Adenosine A₁ Receptor Allosteric Modulators and Antagonists

  摘要：

  A pharmacophore-based screen identified 32 compounds including ethyl 5-amino-3-(4-tert-butylphenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate (8) as a new allosteric modulator of the adenosine A(1) receptor (A(1)AR). On the basis of this lead, various derivatives were prepared and evaluated for activity at the human A(1)AR. A number of the test compounds allosterically stabilized agonist-receptor-G protein ternary complexes in dissociation kinetic assays, but were found to be more potent as antagonists in subsequent functional assays of ERK1/2 phosphorylation. Additional experiments on the most potent antagonist, 13b, investigating A(1)AR-mediated [S-35]GTP gamma S binding and [H-3]CCPA equilibrium binding confirmed its antagonistic mode of action and also identified inverse agonism. This study has thus identified a new class of A(1)AR antagonists that can also recognize the receptor's allosteric site with lower potency.

  DOI：

  10.1021/jm800557d

文献信息

• 2-Aminothienopyridazines as Novel Adenosine A₁ Receptor Allosteric Modulators and Antagonists
  作者：Gemma N. Ferguson、Celine Valant、James Horne、Heidi Figler、Bernard L. Flynn、Joel Linden、David K. Chalmers、Patrick M. Sexton、Arthur Christopoulos、Peter J. Scammells

  DOI：10.1021/jm800557d

  日期：2008.10.9

  A pharmacophore-based screen identified 32 compounds including ethyl 5-amino-3-(4-tert-butylphenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate (8) as a new allosteric modulator of the adenosine A(1) receptor (A(1)AR). On the basis of this lead, various derivatives were prepared and evaluated for activity at the human A(1)AR. A number of the test compounds allosterically stabilized agonist-receptor-G protein ternary complexes in dissociation kinetic assays, but were found to be more potent as antagonists in subsequent functional assays of ERK1/2 phosphorylation. Additional experiments on the most potent antagonist, 13b, investigating A(1)AR-mediated [S-35]GTP gamma S binding and [H-3]CCPA equilibrium binding confirmed its antagonistic mode of action and also identified inverse agonism. This study has thus identified a new class of A(1)AR antagonists that can also recognize the receptor's allosteric site with lower potency.