ethyl (3R)-9,10-difluoro-2,3-dihydro-3-[(tetrahydropyran-2-yloxy)methyl]-7-oxo-7H-pyrido[1,2,3-de]benzoxazine-6-carboxylate | 874151-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl (3R)-9,10-difluoro-2,3-dihydro-3-[(tetrahydropyran-2-yloxy)methyl]-7-oxo-7H-pyrido[1,2,3-de]benzoxazine-6-carboxylate
• CAS: 874151-62-9
• 化学式: C₂₀H₂₁F₂NO₆
• 分子量: 409.387
• InChiKey: HBOWYFAZNIWYMY-VPHXOMNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.93
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.99
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl (3R)-9,10-difluoro-2,3-dihydro-3-[(tetrahydropyran-2-yloxy)methyl]-7-oxo-7H-pyrido[1,2,3-de]benzoxazine-6-carboxylate 在 对甲苯磺酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以92%的产率得到(-)-ethyl 9,10-difluoro-2,3-dihydro-3-hydroxymethyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylate
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Novel Pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic Acid Derivatives Carrying the 3-Cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl Group as a C-10 Substituent

  摘要：

  Novel pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid derivatives 5-9 carrying a 3-cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl moiety at the C-10 position were synthesized and their in vitro antibacterial activity, intravenous single-dose toxicity, convulsion inductive ability, and phototoxicity were evaluated. It appeared evident that compounds 5a, 6a, 8a, and 9a, which have a cis-oriented 4-methyl or 4-fluoro-3-cyclopropylaminomethyl-1-pyrrolidinyl moiety at the C-10 position, exhibited 2- to 16-fold more potent in vitro antibacterial activity than clinafloxacin against quinolone-resistant Gram-positive clinical isolates. Furthermore, it was obvious that introduction of a fluorine atom to the C-4 position of the 3-cyclopropylaminomethyl-1-pyrrolidinyl moiety reduced intraveneous single-dose acute toxicity and the convulsion inductive ability, and introduction of a fluorine atom to the C-3 methyl group of the pyridobenzoxazine nucleus eliminated the phototoxicity.

  DOI：

  10.1021/jm701428b
• 作为产物：
  描述：

  ethyl 3-[(2R)-1-hydroxy-3-(tetrahydropyran-2-yloxy)prop-2-ylamino]-2-(2,3,4,5-tetrafluorobenzoyl)acrylate 在 potassium fluoride 作用下， 以 二甲基亚砜 为溶剂， 反应 5.0h， 以62%的产率得到ethyl (3R)-9,10-difluoro-2,3-dihydro-3-[(tetrahydropyran-2-yloxy)methyl]-7-oxo-7H-pyrido[1,2,3-de]benzoxazine-6-carboxylate
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Novel Pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic Acid Derivatives Carrying the 3-Cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl Group as a C-10 Substituent

  摘要：

  Novel pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid derivatives 5-9 carrying a 3-cyclopropylaminomethyl-4-substituted-1-pyrrolidinyl moiety at the C-10 position were synthesized and their in vitro antibacterial activity, intravenous single-dose toxicity, convulsion inductive ability, and phototoxicity were evaluated. It appeared evident that compounds 5a, 6a, 8a, and 9a, which have a cis-oriented 4-methyl or 4-fluoro-3-cyclopropylaminomethyl-1-pyrrolidinyl moiety at the C-10 position, exhibited 2- to 16-fold more potent in vitro antibacterial activity than clinafloxacin against quinolone-resistant Gram-positive clinical isolates. Furthermore, it was obvious that introduction of a fluorine atom to the C-4 position of the 3-cyclopropylaminomethyl-1-pyrrolidinyl moiety reduced intraveneous single-dose acute toxicity and the convulsion inductive ability, and introduction of a fluorine atom to the C-3 methyl group of the pyridobenzoxazine nucleus eliminated the phototoxicity.

  DOI：

  10.1021/jm701428b