1-[4-Methoxy-3-[(tetrahydro-3-furanyl)oxy]phenyl]ethanone | 1092388-65-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-Methoxy-3-[(tetrahydro-3-furanyl)oxy]phenyl]ethanone
• 英文别名: 1-[4-methoxy-3-(oxolan-3-yloxy)phenyl]ethanone
• CAS: 1092388-65-2
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: RUKOULJOAKXVNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[4-Methoxy-3-[(tetrahydro-3-furanyl)oxy]phenyl]ethanone 在 溴 作用下， 以 氯仿 为溶剂， 生成
  参考文献：
  名称：

  Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors

  摘要：

  An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.01.057
• 作为产物：
  描述：

  3-羟基四氢呋喃 、 4-甲氧基-3-羟基苯乙酮 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 16.0h， 生成 1-[4-Methoxy-3-[(tetrahydro-3-furanyl)oxy]phenyl]ethanone
  参考文献：
  名称：

  Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors

  摘要：

  An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.01.057

文献信息

• Pyrazolone Derivative
  申请人：Gomi Noriaki

  公开号：US20100324091A1

  公开（公告）日：2010-12-23

  A pyrazolone derivative represented by formula (I) below: wherein R 1 to R 3 are the same as defined in claims; or an optical isomer, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is provided. The novel pyrazolone derivative according to the present invention has a PAI-1 production inhibitory activity, a tissue fibrosis inhibitory activity, and a fibrolytic activity, and is effective for preventing and/or treating tissue fibrotic diseases (lung fibrosis, kidney fibrosis, etc.) and diseases of which a pathological thrombus becomes the cause, such as ischemic cardiac diseases (cardiac infarction and angina pectoris), atrial thrombus, lung embolism, deep thrombophlebitis, disseminated intravascular clotting, ischemic brain diseases (brain infarction, brain hemorrhage), and arterial sclerosis. In addition, a pharmaceutical agent for preventing and/or treating the disease conditions or the symptoms mediated by plasminogen activator inhibitor-1, comprising the novel pyrazolone derivative according to the present invention is also provided.

  本发明提供了一种由以下式（I）表示的吡唑酮衍生物：其中，R1至R3与权利要求中定义的相同；或其光学异构体、药学上可接受的盐或其水合物或溶剂化物。根据本发明，这种新型的吡唑酮衍生物具有PAI-1生产抑制活性、组织纤维化抑制活性和纤溶活性，对于预防和/或治疗组织纤维化疾病（肺纤维化、肾脏纤维化等）以及由病理性血栓引起的疾病（缺血性心脏病（心肌梗死和心绞痛）、心房血栓、肺栓塞、深静脉血栓性炎症、弥漫性血管内凝血、缺血性脑疾病（脑梗死、脑出血）和动脉硬化）非常有效。此外，本发明还提供了一种用于预防和/或治疗由纤溶酶原激活剂抑制物-1介导的疾病状况或症状的药物制剂，其包括根据本发明的新型吡唑酮衍生物。
• PYRAZOLONE DERIVATIVE
  申请人：Kowa Company, Ltd.

  公开号：EP2172458A1

  公开（公告）日：2010-04-07

  A pyrazolone derivative represented by formula (I) below: wherein R1 to R3 are the same as defined in claims; or an optical isomer, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof is provided. The novel pyrazolone derivative according to the present invention has a PAI-1 production inhibitory activity, a tissue fibrosis inhibitory activity, and a fibrolytic activity, and is effective for preventing and/or treating tissue fibrotic diseases (lung fibrosis, kidney fibrosis, etc.) and diseases of which a pathological thrombus becomes the cause, such as ischemic cardiac diseases (cardiac infarction and angina pectoris), atrial thrombus, lung embolism, deep thrombophlebitis, disseminated intravascular clotting, ischemic brain diseases (brain infarction, brain hemorrhage), and arterial sclerosis. In addition, a pharmaceutical agent for preventing and/or treating the disease conditions or the symptoms mediated by plasminogen activator inhibitor-1, comprising the novel pyrazolone derivative according to the present invention is also provided.

  下式（I）所代表的吡唑酮衍生物： 其中 R1 至 R3 与权利要求中定义的相同；或其光学异构体、药学上可接受的盐或其水合物或溶液。根据本发明的新型吡唑酮衍生物具有 PAI-1 生成抑制活性、组织纤维化抑制活性和纤维分解活性，可有效预防和/或治疗组织纤维化疾病（肺纤维化、肾纤维化等）和病理血栓形成疾病。例如缺血性心脏病（心肌梗塞和心绞痛）、心房血栓、肺栓塞、深部血栓性静脉炎、弥散性血管内凝血、缺血性脑部疾病（脑梗塞、脑出血）和动脉硬化。此外，还提供了一种用于预防和/或治疗由纤溶酶原激活剂抑制剂-1介导的疾病症状的药剂，其中包含根据本发明的新型吡唑酮衍生物。
• PHARMAZEUTISCHE PRÄPARATE
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP0198919A1

  公开（公告）日：1986-10-29
• US5783591A
  申请人：——

  公开号：US5783591A

  公开（公告）日：1998-07-21
• US5998453A
  申请人：——

  公开号：US5998453A

  公开（公告）日：1999-12-07