8-(1-((3,5-difluorophenyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid | 1296271-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-(1-((3,5-difluorophenyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid
• 英文别名: 8-(1-(3,5-difluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid；8-[1-(3,5-difluoroanilino)ethyl]-2-morpholin-4-yl-4-oxochromene-6-carboxylic acid
• CAS: 1296271-57-2
• 化学式: C₂₂H₂₀F₂N₂O₅
• 分子量: 430.408
• InChiKey: PSKDKFPIGKMDGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  8-(1-((3,5-difluorophenyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 生成 8-(1-(3,5-difluorophenylamino)ethyl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one
  参考文献：
  名称：

  [EN] CHROMENONE DERIVATIVES WITH ANTI-TUMOUR ACTIVITY
  [FR] DÉRIVÉS DE CHROMÉNONE À ACTIVITÉ ANTITUMORALE

  摘要：

  这项发明涉及公式（I）的香豆素衍生物或其药用盐，其中R1、R2、R3、R4、R5、R6、R7、R8、n和R9中的每一个具有在描述中先前定义的任何含义；它们的制备方法，含有它们的药物组合物以及它们在制造用于治疗细胞增殖紊乱的药物的药物中的使用。

  公开号：

  WO2011051704A1
• 作为产物：
  描述：

  3-乙酰基-5-溴-4-羟基苯甲酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 氯化亚砜 、 三氟甲磺酸酐 、 水 、 三溴化磷 、 potassium iodide 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 1,2-二氯乙烷 为溶剂， 反应 147.75h， 生成 8-(1-((3,5-difluorophenyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid
  参考文献：
  名称：

  Discovery of (R)-8-(1-(3,5-Difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (AZD8186): A Potent and Selective Inhibitor of PI3Kβ and PI3Kδ for the Treatment of PTEN-Deficient Cancers

  摘要：

  Several studies have highlighted the dependency of PTEN deficient tumors to PI3K beta activity and specific inhibition of PI3Kd has been shown activity against human B-cell cancers. We describe the discovery and optimization of a series of 8-(1-anilino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamides as PI3K beta/d inhibitors, which led to the discovery of the clinical candidate 13, also known as AZD8186. On the basis of the lower lipophilicity of the chromen-4-one core compared to the previously utilized pyrido[1,2-a]pyrimid-4-one core, this series of compounds displayed high metabolic stability and suitable physical properties for oral administration. Compound 13 showed profound pharmacodynamic modulation of p-Akt in PTEN-deficient PC3 prostate tumor bearing mice after oral administration and showed complete inhibition of tumor growth in the mouse PTEN-deficient PC3 prostate tumor xenograft model. 13 was selected as a clinical candidate for treatment of PTEN-deficient cancers and has recently entered phase I clinical trials.

  DOI：

  10.1021/jm501629p

文献信息

• CHROMENONE DERIVATIVES
  申请人：BARLAAM Bernard Christophe

  公开号：US20110098271A1

  公开（公告）日：2011-04-28

  The invention concerns chromenone derivatives of Formula I or a pharmaceutically-acceptable salts thereof, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , n and R 9 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.

  这项发明涉及公式I的香豆素衍生物或其药用盐，其中R1、R2、R3、R4、R5、R6、R7、R8、n和R9中的每一个具有在描述中定义的任何含义；它们的制备方法，含有它们的药物组合物以及它们在制造用于治疗细胞增殖紊乱的药物的药物中的使用。
• Chromenone derivatives
  申请人：AstraZeneca AB

  公开号：US08673906B2

  公开（公告）日：2014-03-18

  The invention concerns chromenone derivatives of Formula I or a pharmaceutically-acceptable salts thereof, wherein each of R1, R2, R3, R4, R5, R6, R7, R8, n and R9 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.

  本发明涉及式I的香豆素衍生物或其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、n和R9中的每一个具有前述描述中定义的任何含义；其制备方法、含有它们的制药组合物以及它们在制造用于治疗细胞增殖性疾病的药物中的应用。
• [EN] PHOSPHOINOSITIDE 3 KINASE BETA INHIBITORS AND COMPOSITIONS AND METHODS THEREOF<br/>[FR] INHIBITEURS DE LA PHOSPHOINOSITIDE 3 KINASE BÊTA ET COMPOSITIONS ET PROCÉDÉS ASSOCIÉS
  申请人：GEODE THERAPEUTICS INC

  公开号：WO2022164812A1

  公开（公告）日：2022-08-04

  The invention provides novel phosphoinositide 3 kinase beta- selective inhibitors and pharmaceutical compositions thereof, as well as methods of their preparation and use, in therapy of various diseases and conditions, such as solid tunors.

  该发明提供了一种新型的磷脂酰肌醇3激酶β选择性抑制剂及其制备和应用方法，用于治疗各种疾病和病况，例如实体肿瘤。同时还提供了相关的制药组合物。
• CHROMENONE DERIVATIVES WITH ANTI-TUMOUR ACTIVITY
  申请人：AstraZeneca AB

  公开号：EP2493870A1

  公开（公告）日：2012-09-05
• CHROMENONE DERIVATIVES WITH ANTI -TUMOUR ACTIVITY
  申请人：AstraZeneca AB

  公开号：EP2493870B1

  公开（公告）日：2014-12-17