1-(2-(4-(2-amino-5-fluoropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-(pyridin-3-yl)-5-(trifluoromethyl)phenyl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(2-(4-(2-amino-5-fluoropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-(pyridin-3-yl)-5-(trifluoromethyl)phenyl)urea
• 英文别名: 1-[2-[4-(2-Amino-5-fluoro-3-pyridyl)phenoxy]pyrimidine-5-yl]-3-[2-(3-pyridyl)-5-(trifluoromethyl)phenyl]urea；1-[2-[4-(2-amino-5-fluoropyridin-3-yl)phenoxy]pyrimidin-5-yl]-3-[2-pyridin-3-yl-5-(trifluoromethyl)phenyl]urea
• 化学式: C₂₈H₁₉F₄N₇O₂
• 分子量: 561.498
• InChiKey: NMYDPHOWOZZONW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  128
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1-(2-(4-(2-amino-5-fluoropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-(pyridin-3-yl)-5-(trifluoromethyl)phenyl)urea 在 盐酸 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 0.17h， 生成 1-{2-[4-(2-amino-5-fluoropyridin-3-yl)phenoxy]pyrimidin-5-yl}-3-[2-(pyridin-3-yl)-5-(trifluoromethyl)phenyl]urea dihydrochioride
  参考文献：
  名称：

  ACID-ADDITION SALT OF Trk-INHIBITING COMPOUND

  摘要：

  为了为Trk相关疾病提供一种预防和/或治疗剂，本发明提供了一种具有选择性Trk抑制活性的化合物，持续抑制NGF血管高渗透性，并且不具有药物相互作用，此外，该化合物在溶解性和对游离碱的吸收性方面表现出色。本发明的化合物具有选择性Trk抑制活性，持续抑制NGF血管高渗透性，不具有药物相互作用，在溶解性和对游离碱的吸收性方面表现出色，因此可作为Trk相关疾病的预防和/或治疗剂。

  公开号：

  US20170240527A1
• 作为产物：
  描述：

  4-羟基苯硼酸频哪醇酯 在 potassium phosphate 、 四(三苯基膦)钯 、 氢气 、 palladium(II) hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 N,N-二甲基乙酰胺 、 水 、 乙酸乙酯 为溶剂， 反应 6.58h， 生成 1-(2-(4-(2-amino-5-fluoropyridin-3-yl)phenoxy)pyrimidin-5-yl)-3-(2-(pyridin-3-yl)-5-(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  ACID-ADDITION SALT OF Trk-INHIBITING COMPOUND

  摘要：

  为了为Trk相关疾病提供一种预防和/或治疗剂，本发明提供了一种具有选择性Trk抑制活性的化合物，持续抑制NGF血管高渗透性，并且不具有药物相互作用，此外，该化合物在溶解性和对游离碱的吸收性方面表现出色。本发明的化合物具有选择性Trk抑制活性，持续抑制NGF血管高渗透性，不具有药物相互作用，在溶解性和对游离碱的吸收性方面表现出色，因此可作为Trk相关疾病的预防和/或治疗剂。

  公开号：

  US20170240527A1

文献信息

• Trk-INHIBITING COMPOUND
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20160000783A1

  公开（公告）日：2016-01-07

  The present invention provides a drug containing a compound having Trk-inhibiting activity as an active ingredient in prophylaxis and/or therapy for Trk-related diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. A compound represented by the general formula (I), wherein all symbols represent the same meanings as described in the specification, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof is useful as a drug component having Trk-inhibiting activity in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

  本发明提供了一种药物，其中包含具有Trk抑制活性的化合物作为预防和/或治疗Trk相关疾病的活性成分，例如疼痛、瘙痒、下尿路功能障碍、哮喘、过敏性鼻炎、炎症性肠病或查加斯病。通式（I）所表示的化合物，其中所有符号都表示规范中描述的相同含义，其盐，N-氧化物，溶剂化物或前药是作为具有Trk抑制活性的药物成分在预防和/或治疗疼痛、瘙痒、下尿路功能障碍、哮喘、过敏性鼻炎、炎症性肠病或查加斯病等疾病中有用的。
• METHOD FOR TREATING CANCER BY COMBINATION OF Trk INHIBITOR AND KINASE INHIBITOR
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP3679932A1

  公开（公告）日：2020-07-15

  An object of the present invention is to provide a combination therapy in which an antitumor effect is enhanced as compared to when a Trk inhibitor or any of various kinase inhibitors is administered alone. A Trk inhibitor, particularly, a compound represented by General Formula (I): wherein all symbols have the same meanings as symbols described in this specification, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof is useful as an active ingredient of a cancer therapeutic agent used in combination with one or more drugs selected from the group consisting of an MEK inhibitor, a CDK4/6 inhibitor, an EGFR inhibitor and a JAK1/2 inhibitor.

  本发明的目的是提供一种联合疗法，与单独使用Trk抑制剂或各种激酶抑制剂中的任何一种相比，该疗法的抗肿瘤效果更强。Trk抑制剂，特别是通式(I)所代表的化合物： 其中所有符号与本说明书中描述的符号具有相同的含义，其盐、其 N-氧化物、其溶液或其原药可作为癌症治疗剂的活性成分，与选自 MEK 抑制剂、CDK4/6 抑制剂、表皮生长因子受体抑制剂和 JAK1/2 抑制剂组成的组中的一种或多种药物联合使用。
• UREA DERIVATIVES AS TRK-INHIBITING COMPOUNDS
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：EP3800183A1

  公开（公告）日：2021-04-07

  The present invention provides a drug containing a compound having Trk-inhibiting activity as an active ingredient in prophylaxis and/or therapy for Trk-related diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. A compound represented by the general formula (I): wherein all symbols represent the same meanings as described in the specification, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof is useful as a drug component having Trk-inhibiting activity in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

  本发明提供了一种含有具有 Trk 抑制活性的化合物的药物，作为预防和/或治疗 Trk 相关疾病（如疼痛、瘙痒、下尿路功能障碍、哮喘、过敏性鼻炎、炎症性肠病或南美锥虫病）的活性成分。通式 (I) 所代表的化合物： 其中所有符号代表的含义与说明书中描述的相同、 其盐、其 N-氧化物、其溶解物或其原药可用作具有 Trk 抑制活性的药物成分，用于预防和/或治疗疼痛、瘙痒、下尿路功能障碍、哮喘、过敏性鼻炎、炎症性肠病或南美锥虫病等疾病。
• Trk-inhibiting compound
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US10300060B2

  公开（公告）日：2019-05-28

  The present invention provides a drug containing a compound having Trk-inhibiting activity as an active ingredient in prophylaxis and/or therapy for Trk-related diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. A compound represented by the general formula (I), wherein all symbols represent the same meanings as described in the specification, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof is useful as a drug component having Trk-inhibiting activity in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease.

  本发明提供了一种含有具有Trk-抑制活性的化合物的药物，作为预防和/或治疗Trk相关疾病（如疼痛、瘙痒、下尿路功能障碍、哮喘、过敏性鼻炎、炎症性肠病或南美锥虫病）的活性成分。通式(I)（其中所有符号代表与说明书所述相同的含义）代表的化合物、其盐、其 N-氧化物、其溶解物或其原药可作为具有 Trk 抑制活性的药物成分，用于预防和/或治疗疼痛、瘙痒、下尿路功能障碍、哮喘、过敏性鼻炎、炎症性肠病或南美锥虫病等疾病。
• Acid-addition salt of Trk-inhibiting compound
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US10399959B2

  公开（公告）日：2019-09-03

  In order to provide a prophylactic and/or therapeutic agent for Trk-related diseases, the present invention provides a compound which has a selective Trk-inhibiting activity and persistently inhibits NGF vascular hyper permeability and does not have a drug interaction and in addition thereto, is excellent in solubility and absorbability against free bases. The compound of the present invention has a selective Trk-inhibiting activity and persistently inhibits NGF vascular hyper permeability and does not have a drug interaction and is excellent in solubility and absorbability against free bases, and is therefore useful as a prophylactic and/or therapeutic agent for Trk-related diseases.

  为了提供一种预防和/或治疗 Trk 相关疾病的药物，本发明提供了一种化合物，该化合物具有选择性 Trk 抑制活性，可持续抑制 NGF 血管高渗透性，且无药物相互作用，此外，该化合物对游离碱的溶解性和可吸收性极佳。本发明的化合物具有选择性Trk-抑制活性，可持续抑制NGF血管高渗透性，且无药物相互作用，对游离碱的溶解性和吸收性极佳，因此可作为预防和/或治疗Trk相关疾病的药物。