4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide fumarate salt | 862366-28-7

• 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: 4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide fumarate salt
• 英文别名: imatinib fumarate；imatinib fumarate salt；4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide fumarate；(E)-but-2-enedioic acid;4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide
• CAS: 862366-28-7
• 化学式: C₄H₄O₄*C₂₉H₃₁N₇O
• 分子量: 609.685
• InChiKey: KVFJZQYIKQFVRW-WLHGVMLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  富马酸 、 伊马替尼 在 甲醇 、 水 作用下， 反应 12.0h， 生成 4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide fumarate salt
  参考文献：
  名称：

  伊马替尼的一系列稳定、亚稳定和不稳定的盐，具有改善的溶解度

  摘要：

  药用盐的形成是提高 API 理化性质的最优选和最有效的方法。该研究的目的是设计和合成一系列新盐以提高伊马替尼（IM）的溶解度。首次获得了丙二酸( S1 )和柠檬酸( S5 )的两种稳定盐，富马酸( S2 )的一种亚稳态盐(S2)，柠檬酸( S3、S4 )的两种不稳定盐。单晶和粉末 X 射线衍射、傅里叶变换红外、差示扫描量热法和热重分析用于表征新型盐。还评估了固体的溶解度和稳定性，以及三种盐（S1、S2、S5) 分别与纯药物在水中和 pH 6.8 缓冲液中相比，溶解度提高了 20 倍以上，溶出速度更快。

  DOI：

  10.1016/j.cclet.2021.10.056

文献信息

• [EN] NOVEL SALTS OF IMATINIB<br/>[FR] NOUVEAUX SELS D'IMATINIB
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2012090221A1

  公开（公告）日：2012-07-05

  The present inventiin discloses pharmaceutically acceptable salts of imatinib of Formula (II) wherein in S represent the acid selected from the group consisting of oxalic acid, ptoluene sulfonic acid, naphthalene sulfonic acid, benzene sulfonic acid, nitric acid, phosphoric acid, acetic acid, maleic acid, fumaric acid, amino acids like lysine, lysine HC1, arginine; which forms a salt with imatinib.

  本发明揭示了公式（II）的伊马替尼的药用可接受盐，其中S代表从草酸、对甲苯磺酸、萘磺酸、苯磺酸、硝酸、磷酸、乙酸、马来酸、富马酸、赖氨酸、赖氨酸HCl、精氨酸等氨基酸中选择的酸，与伊马替尼形成盐。
• AEROSOL TYROSINE KINASE INHIBITOR COMPOUNDS AND USES THEREOF
  申请人：WINDWARD PHARMA, INC.

  公开号：US20150044288A1

  公开（公告）日：2015-02-12

  Disclosed herein are formulations of imatinib or a phenylaminopyrimidine derivative compound for aerosolization and use of such formulations for inhaled aerosol administration of imatinib or a phenylaminopyrimidine derivative compound for the prevention or treatment of various fibrotic, carcinogenic, vascular and viral infectious diseases, including diseases associated with the lung, heart, kidney, liver, eye, central nervous system and surgical sites. In some embodiments, formulations and delivery options described herein allow for efficacious local delivery of imatinib or a phenylaminopyrimidine derivative compound or salt thereof. Compositions include all formulations, kits, and device combinations described herein. Methods include inhalation procedures, indications and manufacturing processes for production and use of the compositions described. Also included are methods for identifying compounds and indications that may benefit by reformulation and inhalation administration.

  本文公开了伊马替尼或苯基氨基嘧啶衍生物化合物的喷雾制剂，并使用这些制剂进行吸入式喷雾给药，用于预防或治疗各种纤维化、致癌、血管和病毒性感染性疾病，包括与肺、心脏、肾脏、肝脏、眼、中枢神经系统和手术部位相关的疾病。在某些实施例中，本文所描述的制剂和给药选项允许对伊马替尼或其苯基氨基嘧啶衍生物化合物或其盐进行有效的局部给药。组合物包括本文所述的所有制剂、套件和设备组合。方法包括吸入程序、适应症和制造过程，用于生产和使用所述组合物。还包括识别可能通过重新制剂和吸入给药获益的化合物和适应症的方法。
• [EN] SALT FORMS OF 4-(4-METHYLPIPERAZIN-1-YLMETHYL)-n-[4-METHYL-3-(4-PYRIDIN-3-YL)PYRIMIDIN-2-YLAMINO)PHENYL]-BENZAMIDE<br/>[FR] FORMES SALINES DE 4-(4-METHYLPIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL)PYRIMIDIN-2-YLAMINO)PHENYL]-BENZAMIDE
  申请人：NOVARTIS AG

  公开号：WO2005075454A3

  公开（公告）日：2006-07-27
• INHALED IMATINIB FOR TREATMENT OF PULMONARY ARTERIAL HYPERTENSION (PAH)
  申请人：AVALYN PHARMA INC.

  公开号：US20210093569A1

  公开（公告）日：2021-04-01

  Disclosed herein are formulations of imatinib or a phenylaminopyrimidine derivative compound for aerosolization and use of such formulations for inhaled aerosol administration of imatinib or a phenylaminopyrimidine derivative compound for the prevention or treatment of various fibrotic, carcinogenic, vascular and viral infectious diseases, including diseases associated with the lung, heart, kidney, liver, eye, central nervous system and surgical sites. In some embodiments, formulations and delivery options described herein allow for efficacious local delivery of imatinib or a phenylaminopyrimidine derivative compound or salt thereof. Compositions include all formulations, kits, and device combinations described herein. Methods include inhalation procedures, indications and manufacturing processes for production and use of the compositions described. Also included are methods for identifying compounds and indications that may benefit by reformulation and inhalation administration.
• INHALED IMATINIB FOR PULMONARY HYPERTENSION
  申请人：United Therapeutics Corporation

  公开号：US20220152025A1

  公开（公告）日：2022-05-19

  Methods of treatment of pulmonary hypertension comprising dry powder inhalation administration of imatinib, a pharmaceutically acceptable salt, or a derivative thereof, are provided. Dry powder inhalable compositions comprising imatinib, a pharmaceutically acceptable salt, or a derivative thereof, are also provided as well as methods of making the same.