2-(difluoromethoxy)-4-(4-methylpiperazin-1-yl)aniline | 1817793-27-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(difluoromethoxy)-4-(4-methylpiperazin-1-yl)aniline
• CAS: 1817793-27-3
• 化学式: C₁₂H₁₇F₂N₃O
• 分子量: 257.283
• InChiKey: KNAXUMBCKMZXGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(difluoromethoxy)-4-(4-methylpiperazin-1-yl)aniline 、 3-((2,5-dichloropyrimidin-4-yl)amino)thiophene-2-carboxamide 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 16.0h， 以87%的产率得到3-((5-chloro-2-((2-(difluoromethoxy)-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)thiophene-2-carboxamide
  参考文献：
  名称：

  [EN] THIENYL AND CYCLOALKYL AMINOPYRIMIDINE COMPOUNDS AS INHIBITORS OF NUAK KINASES, COMPOSITIONS AND USES THEREOF
  [FR] COMPOSÉS THIÉNYL ET CYCLOALKYL AMINOPYRIMIDINES UTILISÉS COMME INHIBITEURS DE KINASES NUAK, COMPOSITIONS ET UTILISATIONS DE CEUX-CI

  摘要：

  本申请涉及式（I）化合物或其药学上可接受的盐、溶剂或前药，以及包含这些化合物或其药学上可接受的盐、溶剂或前药的组合物，以及在治疗可通过抑制或阻断NUAK激酶来治疗的疾病、紊乱或病况方面的各种用途，例如癌症和纤维化。

  公开号：

  WO2022147620A1

文献信息

• [EN] PROGNOSTIC BIOMARKERS FOR TTK INHIBITOR CHEMOTHERAPY<br/>[FR] BIOMARQUEURS PRONOSTIQUES POUR CHIMIOTHÉRAPIE BASÉE SUR UN INHIBITEUR DE TTK
  申请人：NETHERLANDS TRANSLATIONAL RES CENTER B V

  公开号：WO2016166255A1

  公开（公告）日：2016-10-20

  The present invention provides a method for identifying a tumor - in a human individual or in an animal - that is susceptible to treatment with a TTK inhibitor, said method comprising: a] providing a sample of a tumor; b] determining the presence of a mutated CTNNB1 gene in said tumor sample, wherein said mutation is located in exon 3 of CTNNB1 and whereby the presence of a mutated CTNNB1 gene indicates that the tumor is susceptible to treatment with a TTK inhibitor. In an alternative aspect, step b] of the above defined method is replaced by the step of determining the presence of a mutated CTNNB1 protein in said tumor sample, wherein said mutation is located in exon 3 of CTNNB1 and whereby the presence of a mutated CTNNB1 protein indicates that the tumor is susceptible to treatment with a TTK inhibitor. In a further alternative, step b] comprises determining an altered expression of a CTNNB1 regulated gene, whereby an altered expression of a CTNNB1 regulated gene indicates that the tumor is susceptible to treatment with a TTK inhibitor.

  本发明提供了一种用于识别易受TTK抑制剂治疗的人体或动物肿瘤的方法，所述方法包括：a] 提供肿瘤样本；b] 确定肿瘤样本中是否存在突变的CTNNB1基因，其中所述突变位于CTNNB1的第3外显子中，并且存在突变的CTNNB1基因表明肿瘤易受TTK抑制剂治疗。在另一种方面，上述定义方法的步骤b] 被替换为确定肿瘤样本中是否存在突变的CTNNB1蛋白，其中所述突变位于CTNNB1的第3外显子中，并且存在突变的CTNNB1蛋白表明肿瘤易受TTK抑制剂治疗。在进一步的替代方案中，步骤b] 包括确定CTNNB1调控基因的表达改变，其中CTNNB1调控基因的表达改变表明肿瘤易受TTK抑制剂治疗。
• [EN] ISOINDOLINONE AMINOPYRIMIDINE COMPOUNDS AS INHIBITORS OF NUAK KINASES, COMPOSITIONS AND USES THEREOF<br/>[FR] COMPOSÉS D'AMINOPYRIMIDINE D'ISOINDOLINONE EN TANT QU'INHIBITEURS DE KINASES NUAK, LEURS COMPOSITIONS ET UTILISATIONS
  申请人：ONTARIO INSTITUTE FOR CANCER RES OICR

  公开号：WO2022147622A1

  公开（公告）日：2022-07-14

  The present application relates to compounds of Formula (I) or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, and various uses in the treatment of diseases, disorders or conditions that are treatable by inhibiting or blocking NUAK kinase, such as cancers and fibrosis.

  本申请涉及公式（I）的化合物或其药学上可接受的盐、溶剂化物和/或前药，以及包含这些化合物或药学上可接受的盐、溶剂化物和/或前药的组合物，并用于治疗可通过抑制或阻止NUAK激酶来治疗的疾病、紊乱或情况，例如癌症和纤维化。
• Prognostic biomarkers for TTK inhibitor chemotherapy
  申请人：NETHERLANDS TRANSLATIONAL RESEARCH CENTER B.V.

  公开号：US11208696B2

  公开（公告）日：2021-12-28

  A method for identifying a tumor that is susceptible to treatment with a TTK inhibitor, including: a) providing a sample of a tumor; b) determining the presence of a mutated CTNNB1 gene in the sample, wherein the mutation is located in exon 3 of CTNNB1 and the presence of a mutated CTNNB1 gene indicates the tumor is susceptible to treatment with a TTK inhibitor. Alternatively, step b) is replaced by the step of determining the presence of a mutated CTNNB1 protein in the sample, wherein the mutation is located in exon 3 of CTNNB1 and the presence of a mutated CTNNB1 protein indicates the tumor is susceptible to treatment with a TTK inhibitor. In a further alternative, step b) includes determining an altered expression of a CTNNB1 regulated gene, whereby an altered expression of a CTNNB1 regulated gene indicates the tumor is susceptible to treatment with a TTK inhibitor.

  一种鉴定易受TTK抑制剂治疗的肿瘤的方法，包括：a)提供肿瘤样本；b)确定样本中是否存在突变的CTNNB1基因，其中突变位于CTNNB1的第3外显子，突变的CTNNB1基因的存在表明肿瘤易受TTK抑制剂的治疗。或者，将步骤 b) 替换为确定样本中是否存在突变的 CTNNB1 蛋白，其中突变位于 CTNNB1 的第 3 号外显子，且突变的 CTNNB1 蛋白的存在表明肿瘤易受 TTK 抑制剂的治疗。在另一种选择中，步骤 b) 包括确定 CTNNB1 受控基因表达的改变，其中 CTNNB1 受控基因表达的改变表明肿瘤易受 TTK 抑制剂的治疗。
• (5,6-DIHYDRO)PYRIMIDO[4,5-E]INDOLIZINES
  申请人：Netherlands Translational Research Center B.V.

  公开号：EP3129374B1

  公开（公告）日：2018-12-19
• PROGNOSTIC BIOMARKERS FOR TTK INHIBITOR CHEMOTHERAPY
  申请人：Netherlands Translational Research Center B.V.

  公开号：EP3283642A1

  公开（公告）日：2018-02-21