3-([1,2,4]triazolo[4,3-a]pyridin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide | 1416241-23-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-([1,2,4]triazolo[4,3-a]pyridin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide
• 英文别名: 3-(1,2,4-triazole[4,3-a]pyridine-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazine-1-yl)methyl)-3-trifluoromethylphenyl)benzamide；Pf-114；4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)ethynyl]benzamide
• CAS: 1416241-23-0
• 化学式: C₂₉H₂₇F₃N₆O
• 分子量: 532.568
• InChiKey: SLIVDYMORZGPLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-碘-4-甲基-N-[4-[(4-甲基-1-哌嗪基)甲基]-3-(三氟甲基)苯基]苯甲酰胺 、 3-ethynyl-[1,2,4]triazolo[4,3-a]pyridine 在 3-ethynyl-[1,2,4]triazolo[4,3-a]pyridine 作用下， 生成 3-([1,2,4]triazolo[4,3-a]pyridin-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide
  参考文献：
  名称：

  [EN] ACETYLENE DERIVATIVE HAVING ANTINEOPLASTIC ACTIVITY
  [FR] DÉRIVÉ D'ACÉTYLÈNE AYANT UNE ACTIVITÉ ANTINÉOPLASIQUE

  摘要：

  本发明涉及具有通式I的芳香环二取代乙块衍生物，包含该化合物的药物组合物，以及该化合物和药物组合物用于治疗和/或预防肿瘤的用途，其中A、B、T、M、Ra、Rb、Rt、m、n和p如本文所定义。

  公开号：

  WO2013170774A1

文献信息

• [EN] NOVEL CRYSTALLINE SALT FORMS OF 3-(1,2,4-TRIAZOLO[4,3-A]PYRIDINE-3-YLETHYNYL)-4-METHYL-N-(4-((4-METHYLPIPERAZIN-1-YL)METHYL)-3-TRIFLUOROMETHYLPHENYL)BENZAMIDE FOR MEDICAL APPLICATION<br/>[FR] NOUVELLES FORMES DE SEL CRISTALLIN DU 3-(1,2,4-TRIAZOLO[4,3-A]PYRIDIN-3-YLÉTHYNYL)-4-MÉTHYL-N-(4-((4-MÉTHYLPIPÉRAZIN-1-YL)MÉTHYL)-3-TRIFLUOROMÉTHYLPHÉNYL)BENZAMIDE POUR UNE APPLICATION MÉDICALE
  申请人：LTD LIABILITY COMPANY «FUSION PHARMA»

  公开号：WO2017184032A1

  公开（公告）日：2017-10-26

  The invention relates to the organic chemistry, pharmacology and medicine, and concerns the prevention and treatment of human and animal diseases associated with the disruption of the activity of various kinases, in particular Abl kinase, for example diseases such as leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphocytic leukemia, breast cancer, non-small cell lung cancer, gastrointestinal stromal tumors, ovarian cancer, lymphoma, using a new salt form of 3-(1,2,4-triazolo[4,3-a]pyridine-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-trifluoromethylphenyl)benzamide. The salt of this compound with methanesulfonic acid, formula (I), or its hydrate, solvate, as well as polymorphic modifications that have the ability to inhibit the activity of kinases, in particular Abl kinases. The present invention also relates to pharmaceutical compositions comprising a therapeutically effective amount of a salt of the invention, to a method for preparing a crystalline salt of the invention, as well as to a method for treating oncological diseases in a subject.

  本发明涉及有机化学、药理学和医学，涉及预防和治疗与各种激酶活性紊乱相关的人类和动物疾病，特别是Abl激酶，例如白血病、急性髓性白血病、慢性髓性白血病、急性淋巴细胞白血病、乳腺癌、非小细胞肺癌、胃肠间质瘤、卵巢癌、淋巴瘤，使用3-（1,2,4-三唑[4,3-a]吡啶-3-基乙炔基）-4-甲基-N-（4-（（4-甲基哌嗪-1-基）甲基）-3-三氟甲基苯基）苯甲酰胺的新盐形式。该化合物与甲磺酸的盐，公式（I）或其水合物、溶剂化合物以及具有抑制激酶活性，特别是Abl激酶活性的多态修饰形式。本发明还涉及包含本发明盐的治疗有效量的药物组合物，制备本发明晶体盐的方法，以及治疗受试者肿瘤疾病的方法。
• Protein Kinase Inhibitors (Variants), Use Thereof in Treating Oncological Diseases and a Pharmaceutical Composition Based Thereon
  申请人：Obshchestvo s ogranichennoy otvetstvennostyou "Fusion Pharma"

  公开号：US20140213592A1

  公开（公告）日：2014-07-31

  The present invention relates to the treatment of oncological, chronic inflammatory and similar diseases with the aid of new families of chemical compounds having improved efficiency with regard to the inhibition of Abl kinase and mutant forms thereof, as well as other therapeutically significant kinases. It describes protein kinase inhibitors in the form of compounds of general formula (I) and compounds of general formula (II), or a tautomer, an individual isomer, a mixture of isomers, a pharmaceutically acceptable salt, a solvate or a hydrate thereof.

  本发明涉及使用新的化学化合物家族辅助治疗肿瘤、慢性炎症和类似疾病，这些化合物家族在抑制Abl激酶及其突变形式以及其他具有治疗意义的激酶方面具有提高的效率。本发明描述了蛋白激酶抑制剂，其形式为通式(I)和通式(II)的化合物，或其互变异构体、单个异构体、异构体混合物、药学上可接受的盐、溶剂或其水合物。
• [EN] ACETYLENE DERIVATIVE HAVING ANTINEOPLASTIC ACTIVITY<br/>[FR] DÉRIVÉ D'ACÉTYLÈNE AYANT UNE ACTIVITÉ ANTINÉOPLASIQUE
  申请人：SHANGHAI PHARMACEUTICALS HOLDING CO LTD

  公开号：WO2013170774A1

  公开（公告）日：2013-11-21

  本发明涉及具有通式I的芳香环二取代乙块衍生物，包含该化合物的药物组合物，以及该化合物和药物组合物用于治疗和/或预防肿瘤的用途，其中A、B、T、M、Ra、Rb、Rt、m、n和p如本文所定义。
• PROTEIN KINASE INHIBITORS (VARIANTS), USE THEREOF IN TREATING ONCOLOGICAL DISEASES AND A PHARMACEUTICAL COMPOSITION BASED THEREON
  申请人：Obshchestvo S Ogranichennoy Otvetstvennostyou "Fusion Pharma"

  公开号：EP2743266A2

  公开（公告）日：2014-06-18

  The present invention relates to the treatment of oncological, chronic inflammatory and similar diseases with the aid of new families of chemical compounds having improved efficiency with regard to the inhibition of Abl kinase and mutant forms thereof, as well as other therapeutically significant kinases. It describes protein kinase inhibitors in the form of compounds of general formula (I) and compounds of general formula (II), or a tautomer, an individual isomer, a mixture of isomers, a pharmaceutically acceptable salt, a solvate or a hydrate thereof.

  本发明涉及借助新系列化合物治疗肿瘤、慢性炎症和类似疾病，这些化合物在抑制 Abl 激酶及其突变形式以及其他具有治疗意义的激酶方面具有更高的效率。它描述了通式（I）化合物和通式（II）化合物或其同分异构体、单个异构体、异构体混合物、药学上可接受的盐、溶液或水合物形式的蛋白激酶抑制剂。
• Crystalline salt forms of 3-(1,2,4-triazolo[4,3-a]pyridine-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-trifluoromethylphenyl)benzamide for medical application
  申请人：LIMITED LIABILITY COMPANY <<FUSION PHARMA>>

  公开号：US11225474B2

  公开（公告）日：2022-01-18

  The invention relates to the organic chemistry, pharmacology and medicine, and concerns the prevention and treatment of human and animal diseases associated with the disruption of the activity of various kinases, in particular Abl kinase, for example diseases such as leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphocytic leukemia, breast cancer, non-small cell lung cancer, gastrointestinal stromal tumors, ovarian cancer, lymphoma, using a new salt form of 3-(1,2,4-triazolo[4,3-a]pyridine-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-trifluoromethylphenyl)benzamide. The salt of this compound with methanesulfonic acid, or its hydrate, solvate, as well as polymorphic modifications that have the ability to inhibit the activity of kinases, in particular Abl kinases. The present invention also relates to pharmaceutical compositions comprising a therapeutically effective amount of a salt of the invention, to a method for preparing a crystalline salt of the invention, as well as to a method for treating oncological diseases in a subject.

  本发明涉及有机化学、药理学和医学，涉及预防和治疗与各种激酶（特别是 Abl 激酶）活性被破坏有关的人类和动物疾病，例如白血病、急性髓性白血病、慢性髓性白血病、急性淋巴细胞白血病、乳腺癌、非小细胞肺癌、胃肠间质瘤、卵巢癌、淋巴瘤等疾病、使用 3-(1,2,4-三唑并[4,3-a]吡啶-3-乙炔基)-4-甲基-N-(4-((4-甲基哌嗪-1-基)甲基)-3-三氟甲基苯基)苯甲酰胺的新盐形式。该化合物与甲磺酸的盐、 或其水合物、溶解物，以及具有抑制激酶（尤其是 Abl 激酶）活性的多晶型修饰。本发明还涉及包含治疗有效量的本发明盐的药物组合物、制备本发明结晶盐的方法以及治疗受试者肿瘤疾病的方法。