5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

• 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: 5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
• 英文别名: 5-(2-(2,5-Difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide；5-[2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide
• 化学式: C₁₇H₁₅F₂N₅O
• 分子量: 343.336
• InChiKey: JBTQGTQNCVBRNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  76.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide 在 一水合肼 、 溶剂黄146 作用下， 反应 4.0h， 生成 5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-(5-methyl-1H-1,2,4-triazol-3-yl)pyrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  FUSED RING HETEROARYL COMPOUNDS AND THEIR USE AS TRK INHIBITORS

  摘要：

  该披露提供了由化学式I或其药用可接受的盐、溶剂化合物、多型体、酯、互变异构体或前药表示的新型化合物。这些化合物可用作Trk的抑制剂，并且在治疗疼痛、癌症、炎症、神经退行性疾病和某些传染病方面是有用的。 在化合物I的某些化合物中，Q为—CH═CR3C(O)NR4R5，—C≡CC(O)NR4R5，或...

  公开号：

  US20160168156A1
• 作为产物：
  描述：

  LOXO101的中间体 在 甲醇 、 sodium tetrahydroborate 、 硫酸 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  FUSED RING HETEROARYL COMPOUNDS AND THEIR USE AS TRK INHIBITORS

  摘要：

  该披露提供了由化学式I或其药用可接受的盐、溶剂化合物、多型体、酯、互变异构体或前药表示的新型化合物。这些化合物可用作Trk的抑制剂，并且在治疗疼痛、癌症、炎症、神经退行性疾病和某些传染病方面是有用的。 在化合物I的某些化合物中，Q为—CH═CR3C(O)NR4R5，—C≡CC(O)NR4R5，或...

  公开号：

  US20160168156A1

文献信息

• SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS TRK KINASE INHIBITORS
  申请人：Allen Shelley

  公开号：US20120108568A1

  公开（公告）日：2012-05-03

  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.

  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。
• 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。
• METHOD OF DIAGNOSING A CANCER FOR A TREATMENT WITH A TRK INHIBITOR
  申请人：Loxo Oncology, Inc.

  公开号：EP3722441A1

  公开（公告）日：2020-10-14

  A variety of different point mutations in NTRK1, NTRK2, and NTRK3 were identified in biopsy samples from a subjects having a variety of different cancers. Provided herein are methods of treating a subject having a cancer, methods of selecting a treatment including a therapeutically effective amount of a Trk inhibitor for a subject, 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 a cancer, methods of determining a subject's risk for developing a cancer, and methods of assisting in the diagnosis of cancer that are based on the identification of a subject having a cell that has at least one of the point mutations in NTRK1, NTRK2, and/or NTRK3, or the determination that a subject has a cell that has at least one of the point mutations in NTRK1, NTRK2, and/or NTRK3. Also provided are kits that allow for the detection of at least one of the point mutations in NTRK1, NTRK2, and/or NTRK3.

  在患有各种不同癌症的受试者的活检样本中发现了NTRK1、NTRK2和NTRK3的各种不同点突变。本文提供了治疗癌症受试者的方法、为受试者选择包括治疗有效量的Trk抑制剂的治疗方法、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的疗效的方法、确定受试者罹患癌症风险的方法，以及辅助诊断癌症的方法，这些方法的基础是鉴定受试者的细胞具有 NTRK1、NTRK2 和/或 NTRK3 中的至少一种点突变，或确定受试者的细胞具有 NTRK1、NTRK2 和/或 NTRK3 中的至少一种点突变。还提供了可检测 NTRK1、NTRK2 和/或 NTRK3 中至少一种点突变的试剂盒。
• Substituted pyrazolo[1,5-a]pyrimidine compounds as Trk kinase inhibitors
  申请人：Array BioPharma, Inc.

  公开号：US10251889B2

  公开（公告）日：2019-04-09

  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： 及其盐类，其中 R1、R2、R3、R4、X、Y 和 n 具有说明书中给出的含义，是 Trk 激酶的抑制剂，可用于治疗可使用 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。