6,8-difluoro-3,4-dihydro-2H-benzo[1,4]oxazine | 939759-10-1

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 6,8-difluoro-3,4-dihydro-2H-benzo[1,4]oxazine
• 英文别名: 6,8-difluoro-3,4-dihydro-2H-1,4-benzoxazine
• CAS: 939759-10-1
• 化学式: C₈H₇F₂NO
• 分子量: 171.146
• InChiKey: GGUQWCUSJRIBEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(bromomethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide 、 6,8-difluoro-3,4-dihydro-2H-benzo[1,4]oxazine 以 N,N-二甲基乙酰胺 为溶剂， 生成 8-[(6,8-difluoro-2,3-dihydro-1,4-benzoxazin-4-yl)methyl]-N,N-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide
  参考文献：
  名称：

  Discovery of a series of 8-(2,3-dihydro-1,4-benzoxazin-4-ylmethyl)-2-morpholino-4-oxo-chromene-6-carboxamides as PI3Kβ/δ inhibitors for the treatment of PTEN-deficient tumours

  摘要：

  We report the discovery and optimisation of a series of 8-(2,3-dihydro-1,4-benzoxazin-4-ylmethyl)-2-morpholino-4-oxo-chromene-6-carboxamides, leading to compound 16 as a potent and selective PI3K beta/delta inhibitor: PI3K beta cell IC50 0.012 mu M (in PTEN null MDA-MB-468 cell) and PI3K delta cell IC50 0.047 mu M (in Jeko-1 B-cell), with good pharmacokinetics and physical properties. In vivo, 16 showed profound pharmacodynamic modulation of AKT phosphorylation in a mouse PTEN-deficient PC3 prostate tumour xenograft after a single oral dose and gave excellent tumour growth inhibition in the same model after chronic oral dosing. Compound 16 was selected as a preclinical candidate for the treatment of PTEN-deficient tumours. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.03.034

文献信息

• NOVEL PHENYL AMIDE OR PYRIDYL AMIDE DERIVATIVES
  申请人：Bissantz Caterina

  公开号：US20100105906A1

  公开（公告）日：2010-04-29

  This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula wherein A 1 , A 2 , B 1 , B 2 and R 1 to R 11 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及公式的新型苯基酰胺或吡啶基酰胺衍生物 其中A1、A2、B1、B2和R1到R11如描述和索赔中所定义，以及其药学上可接受的盐。这些化合物是GPBAR1激动剂，可用作治疗诸如2型糖尿病等疾病的药物。
• NOVEL PHENYL AMIDE OR PYRIDIL AMIDE DERIVATIVES AND THEIR USE AS GPBAR1 AGONISTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2356094A1

  公开（公告）日：2011-08-17
• US8309734B2
  申请人：——

  公开号：US8309734B2

  公开（公告）日：2012-11-13
• [EN] NOVEL PHENYL AMIDE OR PYRIDIL AMIDE DERIVATIVES AND THEIR USE AS GPBAR1 AGONISTS<br/>[FR] NOUVEAUX DÉRIVÉS D'AMIDES PHÉNYLIQUES OU D'AMIDES PYRIDYLIQUES ET LEUR UTILISATION EN TANT AGONISTES DE GPBAR1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2010049302A1

  公开（公告）日：2010-05-06

  This invention relates to novel phenyl amide or pyridyl amide derivatives of the formula (I) wherein A1, A2, B1, B2 and R1 to R11 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and can be used as medicaments for the treatment of diseases such as type II diabetes.