2-chloro-4-(2,3-dihydroindol-1-yl)pyrimidine | 293292-23-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-4-(2,3-dihydroindol-1-yl)pyrimidine
• 英文别名: 2-chloro-4-(indolin-1-yl)pyrimidine；1-(2-chloropyrimidin-4-yl)-2,3-dihydroindole
• CAS: 293292-23-6
• 化学式: C₁₂H₁₀ClN₃
• 分子量: 231.685
• InChiKey: DVXCTFIEGLLGJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(2,3-dihydroindol-1-yl)pyrimidine 在 氯化铵 、 对甲苯磺酸 、 锌 作用下， 以 水 、 丙酮 、 仲丁醇 为溶剂， 反应 12.25h， 生成 2-(4-(N-(5-amino-2-(N,N-dimethylamino)ethyl)-N-methylamino)-2-methoxyanilino)-4-(2,3-dihydroindol-1-yl)pyrimidine
  参考文献：
  名称：

  [EN] SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF THE EGFR TYROSINE KINASE
  [FR] INHIBITEURS SÉLECTIFS DE MUTANTS CLINIQUEMENT IMPORTANTS DE LA TYROSINE KINASE DE L'EGFR

  摘要：

  本发明提供了式（I）的化合物或其亚类结构或种属，或其药学上可接受的盐、酯、溶剂化合物和/或前药，以及用于治疗或改善异常细胞增殖性疾病，如癌症的方法和组合物，其中A、R2、R3、R10、E1、E2、E3、Y和Z如本文所定义。

  公开号：

  WO2017120429A1
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 吲哚啉 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 反应 12.0h， 以20.6%的产率得到2-chloro-4-(2,3-dihydroindol-1-yl)pyrimidine
  参考文献：
  名称：

  [EN] SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF THE EGFR TYROSINE KINASE
  [FR] INHIBITEURS SÉLECTIFS DE MUTANTS CLINIQUEMENT IMPORTANTS DE LA TYROSINE KINASE DE L'EGFR

  摘要：

  本发明提供了式（I）的化合物或其亚类结构或种属，或其药学上可接受的盐、酯、溶剂化合物和/或前药，以及用于治疗或改善异常细胞增殖性疾病，如癌症的方法和组合物，其中A、R2、R3、R10、E1、E2、E3、Y和Z如本文所定义。

  公开号：

  WO2017120429A1

文献信息

• 2,4-diamino-pyrimidine deprivatives having anti-cell proliferative activity
  申请人：AstraZeneca AB

  公开号：US06716831B1

  公开（公告）日：2004-04-06

  A pyrimidine derivative of formula (I) or (I′): wherein: Rx is a substituent as defined within; Q1 is optionally substituted phenyl, and Q1 bears a substituent of formula (Ia) wherein: X, Y1, Y2, Z, n, and m are as defined within; —NQ2 is an optionally substituted heterocyclic moiety containing one hydrogen heteroatom and optionally containing a further heteroatom; or a pharmaceutically acceptable salt in vivo hydrolysable ester thereof; are useful as anti-cancer agents. Processes for their manufacture and pharmaceutical compositions containing them are described.

  公式（I）或（I'）的嘧啶衍生物：其中：Rx是定义内的取代基；Q1是可选取代的苯基，并且Q1带有式（Ia）的取代基，其中：X，Y1，Y2，Z，n和m如定义内；—NQ2是可选取代的杂环基，含有一个氢杂原子，且可选含有另一个杂原子；或其体内可水解酯的药学上可接受的盐；可用作抗癌剂。描述了其制造过程和含有它们的制药组合物。
• NOVEL RHO KINASE INHIBITORS AND METHODS OF USE
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US20140179689A1

  公开（公告）日：2014-06-26

  The subject invention concerns materials and methods for treating diseases and disorders associated with expression of Rho associated kinases (ROCKs). Examples of diseases and disorders contemplated within the scope of the invention include, but are not limited to, oncological disorders, cardiovascular diseases, CNS disorders, and inflammatory disorders. In one embodiment, a method of the invention comprises administering a therapeutically effective amount of one or more compounds of the present invention, or a composition comprising the compounds, to a person or animal in need of treatment. The subject invention also concerns compounds that inhibit ROCKs, and compositions that comprise the inhibitor compounds of the invention. Compounds contemplated within the scope of the invention include, but are not limited to, those compounds shown in Table 5.

  本发明涉及用于治疗与Rho相关激酶（ROCKs）表达相关的疾病和疾病的材料和方法。本发明范围内考虑的疾病和疾病的示例包括但不限于肿瘤学疾病，心血管疾病，中枢神经系统疾病和炎症性疾病。在一种实施方式中，本发明的方法包括向需要治疗的人或动物施用本发明的一种或多种化合物的治疗有效量，或含有该化合物的组合物。本发明还涉及抑制ROCKs的化合物和包含该抑制剂化合物的组合物。本发明范围内考虑的化合物包括但不限于表5中显示的那些化合物。
• PYRIMIDINE OR PYRIDINE COMPOUNDS, PREPARATION METHOD THEREFOR AND PHARMACEUTICAL USES THEREOF
  申请人：Shanghai Shaletech Technology Co., Ltd.

  公开号：EP3216786A1

  公开（公告）日：2017-09-13

  The present invention disclosed a class of pyrimidine or pyridine compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof, preparation method therefor and pharmaceutical compositions and pharmaceutical uses thereof. The compounds can inhibit the variants of EGFR (Epidermis Growth Factor Receptor) proteinases, and therefore can inhibit the growth of a variety of tumor cells effectively. The compounds can be used to prepare antitumor drugs, used for the treatment, combined therapy or prevention of various different cancers. The compounds can overcome the drug resistance induced by the existing first-generation EGFR inhibitors such as gefitinib, erlotinib and so on. Particularly, the compounds can be used to prepare drugs for treating or preventing diseases, disturbances, disorders or conditions mediated by epidermis growth factor receptor variants (such as L858R activated mutants, Exon19 deletion activated mutants and T790M resistant mutants).

  本发明公开了一类嘧啶或吡啶化合物、其药学上可接受的盐、立体异构体、原药和溶液、其制备方法和药物组合物及其药物用途。这些化合物可以抑制表皮生长因子受体蛋白酶的变体，从而有效抑制多种肿瘤细胞的生长。这些化合物可用于制备抗肿瘤药物，用于治疗、联合治疗或预防各种不同的癌症。这些化合物可以克服现有的第一代表皮生长因子受体抑制剂（如吉非替尼、厄洛替尼等）引起的耐药性。特别是，这些化合物可用于制备治疗或预防由表皮生长因子受体变体（如 L858R 激活突变体、Exon19 缺失激活突变体和 T790M 耐药突变体）介导的疾病、紊乱、失调或病症的药物。
• Pyrimidine or pyridine compounds, preparation method therefor and pharmaceutical uses thereof
  申请人：INVENTISBIO SHANGHAI LTD.

  公开号：US10179784B2

  公开（公告）日：2019-01-15

  The present invention disclosed a class of pyrimidine or pyridine compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof, preparation method therefor and pharmaceutical compositions and pharmaceutical uses thereof. See e.g., Formula I below. The compounds can inhibit the variants of EGFR (Epidermis Growth Factor Receptor) proteinases, and therefore can inhibit the growth of a variety of tumor cells effectively. The compounds can be used to prepare antitumor drugs, used for the treatment, combined therapy or prevention of various different cancers. The compounds can overcome the drug resistance induced by the existing first-generation EGFR inhibitors such as gefitinib, erlotinib and so on. Particularly, the compounds can be used to prepare drugs for treating or preventing diseases, disturbances, disorders or conditions mediated by epidermis growth factor receptor variants (such as L858R activated mutants, Exon19 deletion activated mutants and T790M resistant mutants).

  本发明公开了一类嘧啶或吡啶化合物、其药学上可接受的盐、立体异构体、原药和溶液剂、其制备方法和药物组合物及其药物用途。参见下文式 I。这些化合物可以抑制表皮生长因子受体蛋白酶的变体，因此可以有效抑制多种肿瘤细胞的生长。这些化合物可用于制备抗肿瘤药物，用于治疗、联合治疗或预防各种不同的癌症。这些化合物可以克服现有的第一代表皮生长因子受体抑制剂（如吉非替尼、厄洛替尼等）引起的耐药性。特别是，这些化合物可用于制备治疗或预防由表皮生长因子受体变体（如 L858R 激活突变体、Exon19 缺失激活突变体和 T790M 耐药突变体）介导的疾病、紊乱、失调或病症的药物。
• Selective inhibitors of clinically important mutants of the EGFR tyrosine kinase
  申请人：CS PHARMATECH LIMITED

  公开号：US10435388B2

  公开（公告）日：2019-10-08

  The present invention provides compounds of Formula (I) or a subgeneric structure or species thereof or a pharmaceutically acceptable salt, ester, solvate, and/or prodrug thereof and methods and compositions for treating or ameliorating abnormal cell proliferative disorders, such as cancer, wherein A, R2, R3, R10, E1, E2, E3, Y, and Z are as defined herein.

  本发明提供了式(I)化合物或其亚属结构或种类或其药学上可接受的盐、酯、溶液剂和/或原药，以及用于治疗或改善异常细胞增殖性疾病（如癌症）的方法和组合物，其中A、R2、R3、R10、E1、E2、E3、Y和Z如本文所定义。