5-amino-3-(4-bromophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylic acid | 1221069-58-4

• 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: 5-amino-3-(4-bromophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylic acid
• 英文别名: 5-amino-3-(4-bromophenyl)-4-oxothieno[3,4-d]pyridazine-1-carboxylic acid
• CAS: 1221069-58-4
• 化学式: C₁₃H₈BrN₃O₃S
• 分子量: 366.195
• InChiKey: AOPYIVKMZDGKOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-amino-3-(4-bromophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylic acid 、 异丙胺 在 BOP reagent 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 4.0h， 以68%的产率得到5-amino-3-(4-bromophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide
  参考文献：
  名称：

  Discovery of Brain-Penetrant, Orally Bioavailable Aminothienopyridazine Inhibitors of Tau Aggregation

  摘要：

  Agents capable of preventing the misfolding and sequestration of the microtubule-stabilizing protein tau into insoluble fibrillar aggregates hold considerable promise for the prevention and/or treatment of neurodegenerative tauopathies such as Alzheimer's disease. Because tauopathies are characterized by amyloidosis that is restricted to the central nervous system (CNS), plausible candidate compounds for in vivo evaluation must both prevent tau fibrillization and achieve significant brain levels. Recently, we reported the discovery of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors and now describe a series of new analogues that are both effective inhibitors of tau fibrillization and display significant brain-to-plasma exposure ratios after administration to mice. Further, two of the most promising examples, 15 and 16, were found to reach significant brain exposure levels following oral administration. Taken together, these results suggest that examples from the ATPZ class hold promise as candidates for in vivo efficacy studies in animal models of neurodegenerative tauopathies.

  DOI：

  10.1021/jm100138f
• 作为产物：
  描述：

  ethyl 5-amino-3-(4-bromophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 以77%的产率得到5-amino-3-(4-bromophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylic acid
  参考文献：
  名称：

  Discovery of Brain-Penetrant, Orally Bioavailable Aminothienopyridazine Inhibitors of Tau Aggregation

  摘要：

  Agents capable of preventing the misfolding and sequestration of the microtubule-stabilizing protein tau into insoluble fibrillar aggregates hold considerable promise for the prevention and/or treatment of neurodegenerative tauopathies such as Alzheimer's disease. Because tauopathies are characterized by amyloidosis that is restricted to the central nervous system (CNS), plausible candidate compounds for in vivo evaluation must both prevent tau fibrillization and achieve significant brain levels. Recently, we reported the discovery of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors and now describe a series of new analogues that are both effective inhibitors of tau fibrillization and display significant brain-to-plasma exposure ratios after administration to mice. Further, two of the most promising examples, 15 and 16, were found to reach significant brain exposure levels following oral administration. Taken together, these results suggest that examples from the ATPZ class hold promise as candidates for in vivo efficacy studies in animal models of neurodegenerative tauopathies.

  DOI：

  10.1021/jm100138f

文献信息

• AMINOTHIENOPYRIDAZINE INHIBITORS OF TAU ASSEMBLY
  申请人：Ballatore Carlo

  公开号：US20130029983A1

  公开（公告）日：2013-01-31

  The present invention is directed to methods of inhibiting a tauopathy in a patient by administration of a compound of formula I: Novel aminothienopyridazine compounds are also described.

  本发明涉及通过给予I型化合物来抑制患者的tau病变的方法：还描述了新的氨基噻吩吡嗪化合物。
• [EN] AMINOTHIENOPYRIDAZINE INHIBITORS OF TAU ASSEMBLY<br/>[FR] INHIBITEURS AMINOTHIÉNOPYRIDAZINIQUES DE L'ASSEMBLAGE DES MICROTUBULES SOUS L'EFFET DE LA PROTÉINE TAU
  申请人：UNIV PENNSYLVANIA

  公开号：WO2011037985A1

  公开（公告）日：2011-03-31

  The present invention is directed to methods of inhibiting a tauopathy in a patient by administration of a compound of formula (I): Novel aminothienopyridazine compounds are also described.
• Discovery of Brain-Penetrant, Orally Bioavailable Aminothienopyridazine Inhibitors of Tau Aggregation
  作者：Carlo Ballatore、Kurt R. Brunden、Francesco Piscitelli、Michael J. James、Alex Crowe、Yuemang Yao、Edward Hyde、John Q. Trojanowski、Virginia M.-Y. Lee、Amos B. Smith

  DOI：10.1021/jm100138f

  日期：2010.5.13

  Agents capable of preventing the misfolding and sequestration of the microtubule-stabilizing protein tau into insoluble fibrillar aggregates hold considerable promise for the prevention and/or treatment of neurodegenerative tauopathies such as Alzheimer's disease. Because tauopathies are characterized by amyloidosis that is restricted to the central nervous system (CNS), plausible candidate compounds for in vivo evaluation must both prevent tau fibrillization and achieve significant brain levels. Recently, we reported the discovery of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors and now describe a series of new analogues that are both effective inhibitors of tau fibrillization and display significant brain-to-plasma exposure ratios after administration to mice. Further, two of the most promising examples, 15 and 16, were found to reach significant brain exposure levels following oral administration. Taken together, these results suggest that examples from the ATPZ class hold promise as candidates for in vivo efficacy studies in animal models of neurodegenerative tauopathies.