methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate | 1418287-59-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate
• 英文别名: Methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate；methyl 4-chloro-1-[2-[4-(trifluoromethoxy)phenoxy]ethyl]pyrrolo[3,2-c]pyridine-2-carboxylate
• CAS: 1418287-59-8
• 化学式: C₁₈H₁₄ClF₃N₂O₄
• 分子量: 414.768
• InChiKey: PQSJMXFDRNKYNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate 在 二(三叔丁基膦)钯 、 potassium trimethylsilonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 4-(2-fluoropyridin-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid potassium salt
  参考文献：
  名称：

  [EN] TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
  [FR] INHIBITEURS DE LA KINASE TRKA, COMPOSITIONS EN CONTENANT ET MÉTHODES ASSOCIÉES

  摘要：

  本发明涉及式I和la化合物，它们是原肌球蛋白相关激酶（Trk）家族蛋白激酶抑制剂，因此可用于治疗疼痛、炎症、癌症、再狭窄、动脉粥样硬化、银屑病、血栓形成、与脱髓鞘或髓鞘形成障碍相关的疾病、紊乱、损伤或功能障碍，或与神经生长因子（NGF）受体TrkA异常活性相关的疾病或紊乱。

  公开号：

  WO2013009582A1
• 作为产物：
  描述：

  对三氟甲氧基苯酚 在 sodium hydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 76.0h， 生成 methyl 4-chloro-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylate
  参考文献：
  名称：

  [EN] TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
  [FR] INHIBITEURS DE LA KINASE TRKA, COMPOSITIONS EN CONTENANT ET MÉTHODES ASSOCIÉES

  摘要：

  本发明涉及式I和la化合物，它们是原肌球蛋白相关激酶（Trk）家族蛋白激酶抑制剂，因此可用于治疗疼痛、炎症、癌症、再狭窄、动脉粥样硬化、银屑病、血栓形成、与脱髓鞘或髓鞘形成障碍相关的疾病、紊乱、损伤或功能障碍，或与神经生长因子（NGF）受体TrkA异常活性相关的疾病或紊乱。

  公开号：

  WO2013009582A1

文献信息

• TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF
  申请人：Hanney Barbara

  公开号：US20140155413A1

  公开（公告）日：2014-06-05

  The present invention is directed to compounds of formula I and 1a: which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

  本发明涉及公式I和1a的化合物，它们是肌动蛋白相关激酶（Trk）家族蛋白激酶抑制剂，因此在治疗疼痛、炎症、癌症、再狭窄、动脉粥样硬化、银屑病、血栓形成、与失髓鞘或脱髓鞘有关的疾病、紊乱、损伤或功能障碍，或与神经生长因子（NGF）受体TrkA的异常活动有关的疾病或紊乱的治疗中有用。
• Substituted pyrrolo[3,2-c]pyridines as TrkA kinase inhibitors
  申请人：Hanney Barbara

  公开号：US09102673B2

  公开（公告）日：2015-08-11

  The present invention is directed to compounds of formula I and Ia: which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

  本发明涉及式I和Ia化合物：它们是肌动蛋白相关激酶（Trk）家族蛋白激酶抑制剂，因此在治疗疼痛、炎症、癌症、再狭窄、动脉硬化、银屑病、血栓形成、与失髓鞘化或脱髓鞘化有关的疾病、疾病、损伤或功能障碍或与神经生长因子（NGF）受体TrkA的异常活动有关的疾病或疾病中有用。
• Maximizing Diversity from a Kinase Screen: Identification of Novel and Selective pan-Trk Inhibitors for Chronic Pain
  作者：Shawn J. Stachel、John M. Sanders、Darrell A. Henze、Mike T. Rudd、Hua-Poo Su、Yiwei Li、Kausik K. Nanda、Melissa S. Egbertson、Peter J. Manley、Kristen L. G. Jones、Edward J. Brnardic、Ahren Green、Jay A. Grobler、Barbara Hanney、Michael Leitl、Ming-Tain Lai、Vandna Munshi、Dennis Murphy、Keith Rickert、Daniel Riley、Alicja Krasowska-Zoladek、Christopher Daley、Paul Zuck、Stephanie A. Kane、Mark T. Bilodeau

  DOI：10.1021/jm5006429

  日期：2014.7.10

  We have identified several series of small molecule inhibitors of TrkA with unique binding modes. The starting leads were chosen to maximize the structural and binding mode diversity derived from a high throughput screen of our internal compound collection. These leads were optimized for potency and selectivity employing a structure based drug design approach adhering to the principles of ligand efficiency to maximize binding affinity without overly relying on lipophilic interactions. This endeavor resulted in the identification of several small molecule pan-Trk inhibitor series that exhibit high selectivity for TrkA/B/C versus a diverse panel of kinases. We have also demonstrated efficacy in both inflammatory and neuropathic pain models upon oral dosing. Herein we describe the identification process, hit-to-lead progression, and binding profiles of these selective pan-Trk kinase inhibitors.
• US9102673B2
  申请人：——

  公开号：US9102673B2

  公开（公告）日：2015-08-11
• [EN] TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF<br/>[FR] INHIBITEURS DE LA KINASE TRKA, COMPOSITIONS EN CONTENANT ET MÉTHODES ASSOCIÉES
  申请人：MERCK SHARP & DOHME

  公开号：WO2013009582A1

  公开（公告）日：2013-01-17

  The present invention is directed to compounds of formula I and la: which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

  本发明涉及式I和la化合物，它们是原肌球蛋白相关激酶（Trk）家族蛋白激酶抑制剂，因此可用于治疗疼痛、炎症、癌症、再狭窄、动脉粥样硬化、银屑病、血栓形成、与脱髓鞘或髓鞘形成障碍相关的疾病、紊乱、损伤或功能障碍，或与神经生长因子（NGF）受体TrkA异常活性相关的疾病或紊乱。