N-((R)-2,3-dihydroxypropyl)-5-((R)-2-(5-fluoro-2-(trifluoromethyl)phenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide | 1260841-43-7

• 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: N-((R)-2,3-dihydroxypropyl)-5-((R)-2-(5-fluoro-2-(trifluoromethyl)phenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
• 英文别名: N-((R)-2,3-dihydroxypropyl)-5-((R)-2-(5-fluoro-2-(trifluoromethyl)phenyl) pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide；N-[(2R)-2,3-dihydroxypropyl]-5-[(2R)-2-[5-fluoro-2-(trifluoromethyl)phenyl]pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide
• CAS: 1260841-43-7
• 化学式: C₂₁H₂₁F₄N₅O₃
• 分子量: 467.423
• InChiKey: IVHDXWQQZJTUMV-CXAGYDPISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (R)-5-(2-(5-fluoro-2-(trifluoromethyl)phenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid 、 (R)-3-氨基-1,2-丙二醇 在 crude material 、 acetonitrile-water 作用下， 以to provide the title compound (34 mg, 73% yield)的产率得到N-((R)-2,3-dihydroxypropyl)-5-((R)-2-(5-fluoro-2-(trifluoromethyl)phenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS

  摘要：

  式(I)的化合物及其盐，其中R1、R2、R3、R4、X、Y和n的含义如规范中所述，是Trk激酶的抑制剂，可用于治疗可以用Trk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。

  公开号：

  US20120108568A1

文献信息

• [EN] SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS<br/>[FR] COMPOSÉS PYRAZOLO[1,5-A]PYRIMIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DES TRK KINASES
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2011006074A1

  公开（公告）日：2011-01-13

  Compounds of Formula (I) and salts thereof in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  式（I）的化合物及其盐，其中R1、R2、R3、R4、X、Y和n的含义如规范中所述，是Trk激酶的抑制剂，并且在治疗可以用Trk激酶抑制剂治疗的疾病中具有用处，如疼痛、癌症、炎症、神经退行性疾病和某些传染病。
• Substituted pyrazolo[1,5-a]pyrimidine compounds as Trk kinase inhibitors
  申请人：Allen Shelley

  公开号：US08791123B2

  公开（公告）日：2014-07-29

  Compounds of Formula (I) and salts thereof in which R1, R2, R3, R4, X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  式(I)的化合物及其盐，其中R1、R2、R3、R4、X、Y和n的含义如说明书所述，是Trk激酶的抑制剂，可用于治疗可通过Trk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。
• Substituted Pyrazolo [1,5-A] Pyrimidine Compounds as TRK Kinase Inhibitors
  申请人：Array BioPharma Inc.

  公开号：US20150031667A1

  公开（公告）日：2015-01-29

  Compounds of Formula I: and salts thereof in which R 1 , R 2 , R 3 , R 4 , X, Y and n have the meanings given in the specification, are inhibitors of Trk kinases and are useful in the treatment of diseases which can be treated with a Trk kinase inhibitor such as pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  公式I的化合物及其盐，其中R1、R2、R3、R4、X、Y和n的含义如说明书所述，是Trk激酶的抑制剂，并可用于治疗可以用Trk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。
• INTERMEDIATE COMPOUNDS FOR THE PREPARATION OFSUBSTITUTED PYRAZOLO[1,5-A]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS
  申请人：Array Biopharma, Inc.

  公开号：EP3299372A1

  公开（公告）日：2018-03-28

  Compounds of Formula II, III and IV, wherein R3, R4, Y and n are defined in the claims.

  式 II、III 和 IV 的化合物，其中 R3、R4、Y 和 n 在权利要求中定义。
• 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。