tert-butyl 3-(3-((3S,4R)-1-(2-methoxyethyl)-4-phenyl-3-yl)ureido)-2-phenyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate | 1414552-26-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl 3-(3-((3S,4R)-1-(2-methoxyethyl)-4-phenyl-3-yl)ureido)-2-phenyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate
• 英文别名: US10323022, Example 79；tert-butyl 3-[[(3S,4R)-1-(2-methoxyethyl)-4-phenylpyrrolidin-3-yl]carbamoylamino]-2-phenyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5-carboxylate
• CAS: 1414552-26-3
• 化学式: C₃₀H₃₈N₆O₄
• 分子量: 546.67
• InChiKey: JVBOZNNCWCAOQT-UKILVPOCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-(3-((3S,4R)-1-(2-methoxyethyl)-4-phenyl-3-yl)ureido)-2-phenyl-4,6-dihydropyrrolo[3,4-c]pyrazole-5(2H)-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 1.5h， 生成 1-(5-acetyl-2-phenyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)-3-((3S,4R)-1-(2-methoxyethyl)-4-phenylpyrrolodon-3-yl)urea
  参考文献：
  名称：

  [EN] PYRROLIDINYL UREA AND PYRROLIDINYL THIOUREA COMPOUNDS AS TRKA KINASE INHIBITORS
  [FR] COMPOSÉS DE PYRROLIDINYLE-URÉE ET DE PYRROLIDINYLE THIOURÉE EN TANT QU'INHIBITEURS DE KINASE TRKA

  摘要：

  公开号：

  WO2012158413A3

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。
• 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：The Regents of The University of Colorado, A Body Corporate

  公开号：EP3368039A1

  公开（公告）日：2018-09-05