1-((3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)-3-(3-(imisazo[1,2-a]pyridin-5-yl)-1-methyl-1H-pyrazol-5-yl)urea | 1414551-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 1-((3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)-3-(3-(imisazo[1,2-a]pyridin-5-yl)-1-methyl-1H-pyrazol-5-yl)urea
• 英文别名: Pyrrolidinyl urea derivative 13；1-[(3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl]-3-(5-imidazo[1,2-a]pyridin-5-yl-2-methylpyrazol-3-yl)urea
• CAS: 1414551-92-0
• 化学式: C₂₅H₂₇F₂N₇O₂
• 分子量: 495.532
• InChiKey: SRPJIAHTEPDSEX-LAUBAEHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  88.7
• 氢给体数：
  2
• 氢受体数：
  7

文献信息

• PYRROLIDINYL UREA, PYRROLIDINYL THIOUREA AND PYRROLIDINYL GUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
  申请人：Allen Shelley

  公开号：US20150166564A1

  公开（公告）日：2015-06-18

  Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R 1 , R 2 , R a , R b , R c , R d , X, Y, B, and Ring C are as defined herein, and wherein the Y—B moiety and the NH—C(═X)—NH moiety are in the trans configuration, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  化合物I的公式：或其立体异构体、互变异构体、药学上可接受的盐、溶剂或前药，其中R1、R2、Ra、Rb、Rc、Rd、X、Y、B和环C的定义如本文所述，其中Y-B基团和NH-C（═X）-NH基团处于反式构象，是TrkA激酶的抑制剂，可用于治疗可以通过TrkA激酶抑制剂治疗的疾病，例如疼痛、癌症、炎症、神经退行性疾病和某些传染病。
• Pyrrolidinyl urea, pyrrolidinyl thiourea and pyrrolidinyl guanidine compounds as TrkA kinase inhibitors
  申请人：Array BioPharma Inc.

  公开号：US10323022B2

  公开（公告）日：2019-06-18

  Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R1, R2, Ra, Rb, Rc, Rd, X, Y, B, and Ring C are as defined herein, and wherein the Y—B moiety and the NH—C(═X)—NH moiety are in the trans configuration, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  式 I 的化合物： 或其立体异构体、同系物、或其药学上可接受的盐、或其溶剂或原药，其中 R1、R2、Ra、Rb、Rc、Rd、X、Y、B 和环 C 如本文所定义，且其中 Y-B 分子和 NH-C(═X)-NH 分子为反式构型、是 TrkA 激酶的抑制剂，可用于治疗可使用 TrkA 激酶抑制剂治疗的疾病，如疼痛、癌症、炎症、神经退行性疾病和某些传染性疾病。
• Point mutations in TRK inhibitor-resistant cancer and methods relating to the same
  申请人：Loxo Oncology, Inc.

  公开号：US10370727B2

  公开（公告）日：2019-08-06

  Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment for a subject having a cancer, methods of selecting a subject having a cancer for a treatment that does not include a Trk inhibitor, methods of determining the likelihood that a subject having a cancer will have a positive response to a treatment with a Trk inhibitor, methods of predicting the efficacy of a Trk inhibitor in a subject having cancer, methods of determining a subject's risk for developing a Trk inhibitor-resistant cancer, and methods of determining the presence of a Trk inhibitor-resistant cancer in a subject, based on the detection of a cell from a sample from the subject that has at least one of the the point mutations in NTRK1 and/or NTRK2 and/or NTRK3.

  本文提供了治疗癌症受试者的方法、为癌症受试者选择治疗方法的方法、为不包括Trk抑制剂的治疗方法选择癌症受试者的方法、确定癌症受试者对Trk抑制剂治疗产生阳性反应的可能性的方法、预测Trk抑制剂对癌症受试者疗效的方法、确定受试者罹患Trk抑制剂抗性癌症风险的方法，以及根据从受试者样本中检测到的细胞具有NTRK1和/或NTRK2和/或NTRK3中至少一种点突变，确定受试者存在Trk抑制剂抗性癌症的方法。
• Nitrogen-containing heterocycle and carbocycle derivatives having TrkA inhibitory activity
  申请人：Shionogi & Co., Ltd.

  公开号：US10781210B2

  公开（公告）日：2020-09-22

  The present invention provides a compound having TrkA inhibitory activity, or a pharmaceutically acceptable salt thereof. The present invention relates to a compound represented by Formula (I): wherein ═X is ═O or the like, R5 and R5A are hydrogen atoms or the like, —A— is —NR1— or the like, B is substituted or unsubstituted aromatic carbocyclyl or the like, R1 is substituted or unsubstituted alkyl or the like, R2 is a hydrogen atom or the like, —W— is —CH2— or the like, —WA— is —CH2— or the like, R13 is substituted or unsubstituted aromatic carbocyclyl or the like, R14 is substituted or unsubstituted aromatic heterocyclyl or the like, R15 is substituted or unsubstituted alkyl or the like, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the same.

  本发明提供了一种具有 TrkA 抑制活性的化合物或其药学上可接受的盐。本发明涉及一种由式（I）代表的化合物： 其中═X是═O或类似物，R5和R5A是氢原子或类似物，-A-是-NR1-或类似物，B是取代或未取代的芳香族羰基或类似物，R1是取代或未取代的烷基或类似物，R2是氢原子或类似物，-W-是-CH2-或类似物、-WA-是- -或类似物，R13是取代或未取代的芳香族碳环或类似物，R14是取代或未取代的芳香族杂环或类似物，R15是取代或未取代的烷基或类似物，或其药学上可接受的盐，以及含有这些物质的药物组合物。
• NITROGEN-CONTAINING HETEROCYCLE AND CARBOCYCLE DERIVATIVES HAVING TRKA INHIBITORY ACTIVITY
  申请人：Shionogi & Co., Ltd.

  公开号：EP3412663B1

  公开（公告）日：2022-09-07