methyl 1-oxo-3,4-dihydro-2H-pyrido[1,2-b]indazole-2-carboxylate | 1312815-67-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: methyl 1-oxo-3,4-dihydro-2H-pyrido[1,2-b]indazole-2-carboxylate
• CAS: 1312815-67-0
• 化学式: C₁₃H₁₂N₂O₃
• 分子量: 244.25
• InChiKey: MJTKIASKNAJMOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  60.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-oxo-3,4-dihydro-2H-pyrido[1,2-b]indazole-2-carboxylate 在 水 、 sodium hydride 、 lithium hydroxide 、 lithium hexamethyldisilazane 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 水 、 溶剂黄146 为溶剂， 生成 4-Benzyl-7-methyl-3,4,11,12-tetrazatetracyclo[8.7.0.02,7.012,17]heptadeca-1(17),2,10,13,15-pentaen-5-one
  参考文献：
  名称：

  Phosphodiesterase inhibitors. Part 1: Synthesis and structure–activity relationships of pyrazolopyridine–pyridazinone PDE inhibitors developed from ibudilast

  摘要：

  Ibudilast [1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one] is a nonselective phosphodiesterase inhibitor used clinically to treat asthma. Efforts to selectively develop the PDE3- and PDE4-inhibitory activity of ibudilast led to replacement of the isopropyl ketone by a pyridazinone heterocycle. Structure-activity relationship exploration in the resulting 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazin-3(2H)-ones revealed that the pyridazinone lactam functionality is a critical determinant for PDE3-inhibitory activity, with the nitrogen preferably unsubstituted. PDE4 inhibition is strongly promoted by introduction of a hydrophobic substituent at the pyridazinone N(2) centre and a methoxy group at C-70 in the pyrazolopyridine. Migration of the pyridazinone ring connection from the pyrazolopyridine 30-centre to C-40 strongly enhances PDE4 inhibition. These studies establish a basis for development of potent PDE4-selective and dual PDE3/4-selective inhibitors derived from ibudilast. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.021
• 作为产物：
  描述：

  dimethyl hept-2-ynedioate 在 potassium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 1-oxo-3,4-dihydro-2H-pyrido[1,2-b]indazole-2-carboxylate
  参考文献：
  名称：

  Phosphodiesterase inhibitors. Part 1: Synthesis and structure–activity relationships of pyrazolopyridine–pyridazinone PDE inhibitors developed from ibudilast

  摘要：

  Ibudilast [1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one] is a nonselective phosphodiesterase inhibitor used clinically to treat asthma. Efforts to selectively develop the PDE3- and PDE4-inhibitory activity of ibudilast led to replacement of the isopropyl ketone by a pyridazinone heterocycle. Structure-activity relationship exploration in the resulting 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazin-3(2H)-ones revealed that the pyridazinone lactam functionality is a critical determinant for PDE3-inhibitory activity, with the nitrogen preferably unsubstituted. PDE4 inhibition is strongly promoted by introduction of a hydrophobic substituent at the pyridazinone N(2) centre and a methoxy group at C-70 in the pyrazolopyridine. Migration of the pyridazinone ring connection from the pyrazolopyridine 30-centre to C-40 strongly enhances PDE4 inhibition. These studies establish a basis for development of potent PDE4-selective and dual PDE3/4-selective inhibitors derived from ibudilast. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.021

文献信息

• Factor IXa inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10351558B2

  公开（公告）日：2019-07-16

  The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels. The compounds are selective Factor IXa inhibitors.

  本发明提供了一种式I化合物和包含一种或多种所述化合物的药物组合物，以及使用所述化合物治疗或预防不稳定型心绞痛、难治性心绞痛、心肌梗塞、短暂性脑缺血发作、心房颤动、血栓性中风、栓塞性中风、深静脉血栓形成、弥散性血管内凝血、眼部纤维蛋白堆积、再通血管的再闭塞或再狭窄的方法。这些化合物是选择性因子 IXa 抑制剂。
• Factor IXa Inhibitors
  申请人：MENG Dongfang

  公开号：US20180022747A1

  公开（公告）日：2018-01-25

  The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels. The compounds are selective Factor IXa inhibitors.