1-(1',4-dimethyl-1-phenyl-1H,1'H-[3,4'-bipyrazole]-5-yl)-3-((3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)urea | 1414561-35-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(1',4-dimethyl-1-phenyl-1H,1'H-[3,4'-bipyrazole]-5-yl)-3-((3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)urea
• 英文别名: 1-(1',4-dimethyl-1-phenyl-1H,1'H-[3,4'-bipyrazol]-5-yl)-3-((3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)urea；US10323022, Example 444；1-[(3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl]-3-[4-methyl-5-(1-methylpyrazol-4-yl)-2-phenylpyrazol-3-yl]urea
• CAS: 1414561-35-5
• 化学式: C₂₈H₃₁F₂N₇O₂
• 分子量: 535.597
• InChiKey: UNINZQZAQYZEJM-WIOPSUGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  89.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(1',4-dimethyl-1-phenyl-1H,1'H-[3,4'-bipyrazole]-5-yl)-3-((3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)pyrrolidin-3-yl)urea 在 actinomycetes 、 水 作用下， 以 二甲基亚砜 为溶剂， 反应 72.0h， 以75%的产率得到1-[(3S,4R)-4-(3,4-difluorophenyl)-1-(2-methoxyethyl)-1-oxidopyrrolidin-1-ium-3-yl]-3-[4-methyl-5-(1-methylpyrazol-4-yl)-2-phenylpyrazol-3-yl]urea
  参考文献：
  名称：

  HETEROCYCLE AND CARBOCYCLE DERIVATIVES HAVING TRKA INHIBITORY ACTIVITY

  摘要：

  本发明涉及一种由式（I）表示的化合物：其中-L-为—C(═X)—，或类似的，—Z—为—NR5—，或类似的，—ZA—为—NR5A—，或类似的，—W—为—C(R8R9)n-，—WA—为—C(R3R4)m-，B为取代或未取代的芳香环烃基，或类似的，Y为键，或类似的，环C为取代或未取代的芳香杂环，或类似的，R2为氢原子，或类似的，或其药学上可接受的盐，或包括其的药物组成。

  公开号：

  US20170240512A1

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。
• Heterocycle and carbocycle derivatives having TRKA inhibitory activity
  申请人：Shionogi & Co., Ltd.

  公开号：US10532985B2

  公开（公告）日：2020-01-14

  The present invention relates to a compound represented by Formula (I): wherein -L- is —C(═X)—, or the like, —Z— is —NR5—, or the like, —ZA— is —NR5A—, or the like, —W— is —C(R8R9)n-, —WA— is —C(R3R4)m-, B is substituted or unsubstituted aromatic carbocyclyl, or the like, Y is a bond, or the like, the ring C is a substituted or unsubstituted aromatic heterocycle, or the like, R2 is a hydrogen atom, or the like, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising thereof.

  本发明涉及一种由式（I）表示的化合物： 其中-L-是-C(═X)-，或类似物，-Z-是-NR5-，或类似物，-ZA-是-NR5A-，或类似物，-W-是-C(R8R9)n-，-WA-是-C(R3R4)m-，B是取代或未取代的芳香族碳环，或类似物、Y 是键，或类似物，环 C 是取代或未取代的芳香杂环，或类似物，R2 是氢原子，或类似物，或其药学上可接受的盐，或由其组成的药物组合物。
• Point mutations in TRK inhibitor-resistant cancer and methods relating to the same
  申请人：Loxo Oncology, Inc.

  公开号：US10655186B2

  公开（公告）日：2020-05-19

  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 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、根据从具有 NTRK1 和/或 NTRK2 和/或 NTRK3 中至少一种点突变的受试者样本中检测到的细胞，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 Trk 抑制剂抗性癌症的风险的方法，以及确定受试者中存在 Trk 抑制剂抗性癌症的方法。
• PYRROLIDINYL UREA, PYRROLIDINYL THIOUREA AND PYRROLIDINYL GUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS
  申请人：Array Biopharma, Inc.

  公开号：EP2712358B1

  公开（公告）日：2016-12-21
• POINT MUTATIONS IN TRK INHIBITOR-RESISTANT CANCER AND METHODS RELATING TO THE SAME
  申请人：Loxo Oncology, Inc.

  公开号：US20170260589A1

  公开（公告）日：2017-09-14

  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.