sonidegib diphosphate | 1218778-77-8

• 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: sonidegib diphosphate
• 英文别名: sonidegib phosphate；N-(6-((2R,6S)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)-[1,1'-biphenyl]-3-carboxamide phosphate；N-[6-[(2S,6R)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide;phosphoric acid
• CAS: 1218778-77-8
• 化学式: C₂₆H₂₆F₃N₃O₃*2H₃O₄P
• 分子量: 681.496
• InChiKey: RMTWWCZVPBZSMR-OKZTUQRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  sonidegib 在 磷酸 作用下， 以 水 为溶剂， 生成 sonidegib diphosphate
  参考文献：
  名称：

  LDE225单磷酸盐的晶型及其制备方法

  摘要：

  本发明涉及LDE225单磷酸盐的晶型及其制备方法。本发明的式(Ⅰ)化合物(LDE225)的单磷酸盐的晶型引湿性低，方便保存且稳定性比现有技术中的二磷酸盐更好，能避免药物开发和生产过程中发生转晶的风险。其制备方法简单，成本低廉，对未来该药物的优化和开发具有重要价值。

  公开号：

  CN105906616B

文献信息

• [EN] PROCESS FOR THE PREPARATION OF N-[6-(CIS-2,6-DIMETHYLMORPHOLIN-4-YL)PYRIDINE-3-YL]-2- METHYL-4'-(TRIFIUOROMETHOXY) [1,1' -BIPHENYI]-3-CARBOXAMIDE AND ITS POLYMORPHS THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE N-[6-(CIS-2,6-DIMÉTHYLMORPHOLIN-4-YL)PYRIDINE-3-YL]-2- MÉTHYL-4'-(TRIFLUOROMÉTHOXY) [1,1'-BIPHÉNYL]-3-CARBOXAMIDE ET DE SES POLYMORPHES
  申请人：MSN LABORATORIES PRIVATE LTD

  公开号：WO2017163258A1

  公开（公告）日：2017-09-28

  The present invention relates to process for the preparation of N-[6-(cis-2,6-dimethyl morpholin-4-yl)pyridine-3-yl]-2-methyl-4' -(trifluoromethoxy) [1,1'-biphenyl]-3-carboxamide compound of formula-1, it's salts and their polymorphs thereof.

  本发明涉及一种制备N-[6-(顺-2,6-二甲基吗啉-4-基)吡啶-3-基]-2-甲基-4'-三氟甲氧基[1,1'-联苯]-3-羧酰胺化合物（式-1）、其盐及其多晶形的方法。
• CRYSTAL FORM OF N-[6-(CIS FORM-2,6-DIMETHYLMORPHOLINE-4-GROUP)PYRIDINE-3- GROUP]-2-METHYL-4'-(TRIFLUOROMETHOXY)[1,1'-BIPHENYL]-3- FORMAMIDE MONOPHOSPHATE, AND PREPARATION METHOD THEREFOR
  申请人：Crystal Pharmatech Co., Ltd.

  公开号：EP3279198A1

  公开（公告）日：2018-02-07

  The present disclosure relates to novel crystalline forms of N-[6-(cis -2,6-dimethylmorpholine-4-yl)pyridine-3-yl]-2-methyl)-4'-(trifluoromethoxy) [1,1'-biphenyl]-3-carboxamide monophosphate, and process of preparation thereof. The crystalline form of the monophosphate of a compound of formula (I) has low hygroscopicity, is convenient to store, has better stability than that of diphosphonate in prior art, can avoid the risk of crystal transformation in the development and production of the drug. The preparation method is simple, has low cost, and has important value for further optimization and development of the drug.

  本公开涉及新型结晶形式的 N-[6-(顺式-2,6-二甲基吗啉-4-基)吡啶-3-基]-2-甲基)-4'-(三氟甲氧基)[1,1'-联苯]-3-甲酰胺单磷酸盐及其制备工艺。式（I）化合物单磷酸盐的结晶形态吸湿性低，储存方便，稳定性优于现有技术中的二磷酸盐，可避免药物研发和生产过程中的晶体转化风险。制备方法简单，成本低，对药物的进一步优化和开发具有重要价值。
• Crystaline forms of N-[6-(cis-2,6-dimethylmorpholine-4-yl)pyridine-3-yl]-2-Methyl-4′-(trifluoromethoxy) [1,1′-biphenyl]-3-Methanamide monophosphate, and process of preparation thereof
  申请人：CRYSTAL PHARMATECH CO., LTD.

  公开号：US10266523B2

  公开（公告）日：2019-04-23

  The present disclosure relates to novel crystalline forms of N-[6-(cis-2,6-dimethylmorpholine-4-yl)pyridine-3-yl]-2-methyl-4′-(trifluoromethoxy) [1,1′-biphenyl]-3-carboxamide monophosphate, and process of preparation thereof. The crystalline form of the monophosphate of a compound of formula (I) has low hygroscopicity, is convenient to store, has better stability than that of diphosphonate in prior art, can avoid the risk of crystal transformation in the development and production of the drug. The preparation method is simple, has low cost, and has important value for further optimization and development of the drug.

  本公开涉及 N-[6-(顺式-2,6-二甲基吗啉-4-基)吡啶-3-基]-2-甲基-4′-(三氟甲氧基)[1,1′-联苯]-3-甲酰胺单磷酸盐的新型结晶形式及其制备工艺。式（I）化合物单磷酸盐的晶型吸湿性低，储存方便，稳定性优于现有技术中的二磷酸盐，可避免药物研发和生产中的晶型转变风险。制备方法简单，成本低，对药物的进一步优化和开发具有重要价值。
• Sonidegib phosphate: Smoothened (SMO) receptor antagonist oncolytic
  作者：M. Salati、A. Stathis

  DOI：10.1358/dof.2014.039.010.2207247

  日期：——

  Sonidegib phosphate (LDE-225) is a potent, orally bioavailable, selective inhibitor of smoothened protein, a key downstream transducer of the hedgehog signaling pathway. This pathway has been recently associated with cancer development and progression in several tumor types, and components of this pathway have been regarded as targets for the development of new anticancer agents. In preclinical studies, sonidegib bound to smoothened protein with high affinity, leading to dose-related inhibition of hedgehog signaling, ultimately resulting in tumor growth arrest and regression. In early clinical studies, sonidegib showed a favorable safety profile and demonstrated promising antitumor activity, mainly in basal cell carcinoma and medulloblastoma. Ongoing trials are evaluating sonidegib either alone in selected cancer types or in combination with conventional cytotoxic drugs against a broad range of solid tumors.
• CRYSTALINE FORMS OF N-[6-(CIS-2,6-DIMETHYLMORPHOLINE -4-YL)PYRIDINE-3-YL]-2-METHYL-4'-(TRIFLUOROMETHOXY) [1,1'-BIPHENYL]-3-METHANAMIDE MONOPHOSPHATE, AND PROCESS OF PREPARATION THEREOF
  申请人：CRYSTAL PHARMATECH CO., LTD.

  公开号：US20180170919A1

  公开（公告）日：2018-06-21

  The present disclosure relates to novel crystalline forms of N-[6-(cis-2,6-dimethylmorpholine-4-yl)pyridine-3-yl]-2-methyl-4′-(trifluoromethoxy) [1,1′-biphenyl]-3-carboxamide monophosphate, and process of preparation thereof. The crystalline form of the monophosphate of a compound of formula (I) has low hygroscopicity, is convenient to store, has better stability than that of diphosphonate in prior art, can avoid the risk of crystal transformation in the development and production of the drug. The preparation method is simple, has low cost, and has important value for further optimization and development of the drug.