4,6-dichloro-1-methyl-1H-pyrrolo[2,3-b]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 4,6-dichloro-1-methyl-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 4,6-dichloro-1-methylpyrrolo[2,3-b]pyridine
• 化学式: C₈H₆Cl₂N₂
• 分子量: 201.055
• InChiKey: LBBCLGYLHXLHAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4,6-dichloro-1-methyl-1H-pyrrolo[2,3-b]pyridine 在 盐酸 、 1,1'-双(二苯基膦)二茂铁 、 potassium phosphate 、 palladium diacetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 61.0h， 生成 (2S)-N-(4-chloro-1-methylpyrrolo[2,3-b]pyridin-6-yl)-N-methyl-pyrrolidine-2-carboxamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS FOR USE IN THE TREATMENT OF CANCER
  [FR] COMPOSÉS HÉTÉROCYCLIQUES DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DU CANCER

  摘要：

  该申请涉及杂环酰胺衍生物及其在癌症治疗和预防中的应用，以及含有这些衍生物的组合物和其制备方法。(化学式(I))

  公开号：

  WO2021028643A1
• 作为产物：
  描述：

  硫酸二甲酯 、 4,6-二氯-7-氮杂吲哚 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以66%的产率得到4,6-dichloro-1-methyl-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS FOR USE IN THE TREATMENT OF CANCER
  [FR] COMPOSÉS HÉTÉROCYCLIQUES DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DU CANCER

  摘要：

  该申请涉及杂环酰胺衍生物及其在癌症治疗和预防中的应用，以及含有这些衍生物的组合物和其制备方法。(化学式(I))

  公开号：

  WO2021028643A1

文献信息

• SUBSTITUTED PENTA-FUSED HEXA-HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR, DRUG COMBINATION AND USE THEREOF
  申请人：Xiamen University

  公开号：US20200165246A1

  公开（公告）日：2020-05-28

  A type of substituted penta-fused hexa-heterocyclic compounds having selective inhibition for PIKfyve kinase, a pharmaceutically acceptable salt and pharmaceutically acceptable solvate thereof, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with PIKfyve in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.

  一种替代的五重融合六元杂环化合物，具有对PIKfyve激酶的选择性抑制作用，其药学上可接受的盐及其药学上可接受的溶剂，其制备方法，包括这些化合物的药物组合物，以及在制备用于预防或治疗与PIKfyve相关疾病的药物中使用这些化合物，特别是在制备用于预防或治疗肿瘤生长和转移的药物中。
• SUBSTITUTED PENTA- AND HEXA-HETEROCYCLIC COMPOUNDS, PREPARATION METHOD THEREFOR, DRUG COMBINATION AND USE THEREOF
  申请人：Xiamen University

  公开号：EP3663293A1

  公开（公告）日：2020-06-10

  A type of substituted penta- fused hexa-heterocyclic compounds having selective inhibition for PIKfyve kinase, a pharmaceutically acceptable salt and pharmaceutically acceptable solvate thereof, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with PIKfyve in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.

  一种对PIKfyve激酶具有选择性抑制作用的取代五融合六杂环化合物、其药学上可接受的盐和药学上可接受的溶液、其制备方法、包含这些化合物的药物组合物，以及这些化合物在制造预防或治疗体内PIKfyve相关疾病的药物中的用途，特别是在制造预防或治疗肿瘤生长和转移的药物中的用途。
• Substituted penta-fused hexa-heterocyclic compounds, preparation method therefor, drug combination and use thereof
  申请人：Xiamen University

  公开号：US11352354B2

  公开（公告）日：2022-06-07

  A type of substituted penta-fused hexa-heterocyclic compounds having selective inhibition for PIKfyve kinase, a pharmaceutically acceptable salt and pharmaceutically acceptable solvate thereof, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with PIKfyve in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.

  一种对PIKfyve激酶具有选择性抑制作用的取代五融合六六环化合物、其药学上可接受的盐和药学上可接受的溶液、其制备方法、包含这些化合物的药物组合物，以及这些化合物在制造预防或治疗体内PIKfyve相关疾病的药物中的用途，特别是在制造预防或治疗肿瘤生长和转移的药物中的用途。
• HETEROCYCLIC COMPOUNDS FOR USE IN THE TREATMENT OF CANCER
  申请人：Artios Pharma Limited

  公开号：EP4010080A1

  公开（公告）日：2022-06-15
• Discovery and Identification of Small Molecules as Methuosis Inducers with <i>in Vivo</i> Antitumor Activities
  作者：Wei Huang、Xihuan Sun、Yunzhan Li、Zhixiang He、Li Li、Zhou Deng、Xiaoxing Huang、Shang Han、Ting Zhang、Jiaji Zhong、Zheng Wang、Qingyan Xu、Jianming Zhang、Xianming Deng

  DOI：10.1021/acs.jmedchem.8b00753

  日期：2018.6.28

  Methuosis is a novel nonapoptotic mode of cell death characterized by vacuole accumulation in the cytoplasm. In this article, we describe a series of azaindole-based compounds that cause vacuolization in MDA-MB-231 cells. The most potent vacuole inducer, compound 13 (compound 13), displayed differential cytotoxicities against a broad panel of cancer cell lines, such as MDA-MB-231, A375, HCT116, and MCF-7, but it did not inhibit the growth of the nontumorigenic epithelial cell line MCF-10A. A mechanism study confirmed that the cell death was caused by inducing methuosis. Furthermore, compound 13 exhibited substantial pharmacological efficacy in the suppression of tumor growth in a xenograft mouse model of MDA-MB-231 cells without apparent side effects, which makes this compound the first example of a methuosis inducer with potent in vivo efficacy. These results demonstrate that methuosis inducers might serve as novel therapeutics for the treatment of cancer.