10-Oxo-7,8,9,10-tetrahydropyrido<1,2-b>indazole | 32299-54-0

• 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: 10-Oxo-7,8,9,10-tetrahydropyrido<1,2-b>indazole
• 英文别名: 3,4-dihydro-2H-pyrido[1,2-b]indazol-1-one；3,4-dihydro-2H-pyrido[1,2-b]indazol-1-one
• CAS: 32299-54-0
• 化学式: C₁₁H₁₀N₂O
• 分子量: 186.213
• InChiKey: HEMDNYSCYZXIDJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  34.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  10-Oxo-7,8,9,10-tetrahydropyrido<1,2-b>indazole 在 palladium on activated charcoal Ra-Ni 、 氢气 、 三乙基硼氢化锂 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 24.58h， 生成 1,2,3,4-Tetrahydro-pyrido[1,2-b]indazol-2-ylamine
  参考文献：
  名称：

  融合的氮杂吲哚衍生物：分子设计，合成和体外药理学，可产生优先的多巴胺D3受体激动剂FAUC 725。

  摘要：

  基于分子静电势图相似性的计算研究启动了三环目标化合物1（FAUC 725）和2的合成。针对多巴胺受体亚型D1，D2（长），D2（短），D3和D4的受体结合研究结果表明，氮杂吲哚1的D3亲和力（K（i）= 0.54 nM）与普拉克索铅相似，并且选择性比D2和D4高。有丝分裂发生实验表明D3选择性二丙胺1的实质内在活性。基于（S）-3-PPP的结构，导致测试化合物2的生物等位取代和构象限制无效。

  DOI：

  10.1016/s0960-894x(02)00390-6
• 作为产物：
  描述：

  6-methoxycarbonylhex-5-ynoic acid 在 盐酸 、 水 、 potassium carbonate 、 lithium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 10-Oxo-7,8,9,10-tetrahydropyrido<1,2-b>indazole
  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.
• Phosphodiesterase inhibitors. Part 1: Synthesis and structure–activity relationships of pyrazolopyridine–pyridazinone PDE inhibitors developed from ibudilast
  作者：Robert W. Allcock、Haakon Blakli、Zhong Jiang、Karen A. Johnston、Keith M. Morgan、Georgina M. Rosair、Kazuhiko Iwase、Yasushi Kohno、David R. Adams

  DOI：10.1016/j.bmcl.2011.04.021

  日期：2011.6

  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.
• Fused Azaindole Derivatives: Molecular Design, Synthesis and In Vitro Pharmacology Leading to the Preferential Dopamine D3 Receptor Agonist FAUC 725
  作者：Stefan Löber、Harald Hübner、Peter Gmeiner

  DOI：10.1016/s0960-894x(02)00390-6

  日期：2002.9

  Computational studies based on the similarity of molecular electrostatic potential maps initiated the synthesis of the tricyclic target compounds 1 (FAUC 725) and 2. Receptor binding studies at the dopamine receptor subtypes D1, D2(long), D2(short), D3 and D4 showed that the azaindole 1 revealed D3 affinity (K(i)=0.54 nM) comparable to the lead pramipexole and enhanced selectivity over D2 and D4. Mitogenesis

  基于分子静电势图相似性的计算研究启动了三环目标化合物1（FAUC 725）和2的合成。针对多巴胺受体亚型D1，D2（长），D2（短），D3和D4的受体结合研究结果表明，氮杂吲哚1的D3亲和力（K（i）= 0.54 nM）与普拉克索铅相似，并且选择性比D2和D4高。有丝分裂发生实验表明D3选择性二丙胺1的实质内在活性。基于（S）-3-PPP的结构，导致测试化合物2的生物等位取代和构象限制无效。

表征谱图