8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylic acid | 84427-35-0

• 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: 8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylic acid
• 英文别名: 8-amino-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid；8-amino-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid；8-amino-6,7-difluoro-2-methyl-10-oxo-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5(13),6,8,11-tetraene-11-carboxylic acid
• CAS: 84427-35-0
• 化学式: C₁₃H₁₀F₂N₂O₄
• 分子量: 296.23
• InChiKey: AWXZHYZXTXDEIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylic acid 生成 7-Amino-9-(3-amino-pyrrolidin-1-yl)-8-fluoro-3-methyl-6-oxo-2,3-dihydro-6H-1-oxa-3a-aza-phenalene-5-carboxylic acid
  参考文献：
  名称：

  DOMAGALA, JOHN M.;MICH, THOMAS F.;SANCHEZ, JOSEPH P.

  摘要：

  DOI：
• 作为产物：
  描述：

  氟嗪羧酸 在 palladium on activated charcoal 硫酸 、 氢气 、 potassium nitrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 36.0h， 生成 8-amino-9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido<1,2,3-de><1,4>benzoxazine-6-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological activity of 5-amino- and 5-hydroxyquinolones, and the overwhelming influence of the remote N1-substituent in determining the structure-activity relationship

  摘要：

  A series of 5-amino- and 5-hydroxyquinolone antibacterials substituted at C7 with a select group of common piperazinyl and 3-aminopyrrolidinyl side chains was prepared. These 5-substituted derivatives were compared to the analogous 5-hydrogen compounds for antiinfective activity by using DNA gyrase inhibition, minimum inhibitory concentrations against a variety of bacteria, and in vivo efficacy in the mouse infection model. The influence on the structure-activity relationships of varied substituents at C8 (H, F, Cl) and Ni (ethyl, cyclopropyl, difluorophenyl) was also studied. The results showed that several of the structure-activity conclusions regarding side-chain bulk at C7, the effect of halogen at C8, and the effect of the C5-amino group were greatly influenced by the choice of the N1-substituent. Several outstanding broad spectrum quinolones were identified in this work. In particular, the spectrum and potency of the 7-piperazinyl quinolones could be greatly enhanced by the judicious choice of C5-, C8-, and N1-substitutents.

  DOI：

  10.1021/jm00107a039

文献信息

• 4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivative as antibacterial
  申请人：Warner-Lambert Company

  公开号：US04822801A1

  公开（公告）日：1989-04-18

  Novel naphthyridine-, quinoline- and benzoxazinecarboxylic acids as antibacterial agents are described as well as methods for their manufacture, formulation, and use in treating bacterial infections including the description of certain novel intermediates used in the manufacture of the antibacterial agents.

  描述了新型萘啉基、喹啉基和苯并噁嗪羧酸作为抗菌剂的小说，以及它们的制造、配方和用于治疗细菌感染的方法，包括用于制造抗菌剂的某些新型中间体的描述。
• Cis-substituted aminocycloalkylpyrrolidine derivatives
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：US20020077345A1

  公开（公告）日：2002-06-20

  Antimicrobial agents being excellent in antimicrobial activity and safety. Compounds represented by formula (I), its. salts and hydrates thereof: 1 wherein R 1 represents a hydrogen atom or an alkyl group; R 2 represents a hydrogen atom or an alkyl group; R 3 and R 5 , each represents a hydrogen atom; R 4 represents a hydroxyl group, a halogen atom, a carbamoyl group, an alkyl group, an alkoxyl group or an alkylthio group; R 6 and R 7 , each independently represents a hydrogen atom or an alkyl group; n is an integer of from 1 to 3; R 4 and the substituent on the pyrrolidine ring of the following formula: 2 are located in the cis-configuration; and Q represents a partial structure represented by the following formula: 3

  抗微生物制剂在抗微生物活性和安全性方面表现出色。由式（I）表示的化合物及其盐和水合物：其中R1表示氢原子或烷基；R2表示氢原子或烷基；R3和R5各表示氢原子；R4表示羟基、卤原子、氨基甲酰基、烷基、烷氧基或烷硫基；R6和R7各自独立地表示氢原子或烷基；n为1至3的整数；R4和以下式子中吡咯烷环上的取代基：2位于顺式构型；Q表示以下式子所表示的部分结构：3。
• Antibacterial agents - II
  申请人：Warner-Lambert Company

  公开号：US05097032A1

  公开（公告）日：1992-03-17

  Novel naphthyridine-, quinoline- and benzoxazinecarboxylic acids as antibacterial agents are described as well as methods for their manufacture, formulation, and use in treating bacterial infections including the description of certain novel intermediates used in the manufacture of the antibacterial agents.

  本文描述了新型萘啶、喹啉和苯并噁嗪羧酸作为抗菌剂，以及其制备、配方和治疗细菌感染的使用方法，包括制备抗菌剂所使用的某些新型中间体的描述。
• Substituted-9-fluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acids; substituted-5-amino-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids; substituted-5-amino-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids; derivatives thereof; pharmaceutical compositions comprising the compounds; and processes for producing the compounds
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0172651A1

  公开（公告）日：1986-02-26

  Novel naphthyridine-, quinoline- and benzoxazine carboxylic acids of formula or as antibacterial agents are described as well as methods for their manufacture and formulation. Also disclosed are certain novel intermediates used in the manufacture of the antibacterial agents.

  描述了新颖的式或作为抗菌剂的萘啶、喹啉和苯并噁嗪羧酸及其制造和配制方法。 此外，还公开了用于制造抗菌剂的某些新型中间体。
• PYRIDOBENZOXAZINE DERIVATIVES
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0924213A1

  公开（公告）日：1999-06-23

  This invention provides a derivative, and an excellent pharmaceutical preparation, which has strong antibacterial activity against Gram-negative and Gram-positive bacteria and shows both excellent pharmacokinetics and high safety. Particularly, it provides a pyridobenzoxazine derivative represented by formula (I): wherein R1: a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, in which said alkyl group may have a substituent selected from the group consisting of a hydroxyl group, a halogen atom, an alkylthio group having 1 to 6 carbon atoms and an alkoxyl group having 1 to 6 carbon atoms; R2: a hydrogen atom or an amino group, in which said amino group may have one or two substituents selected from the group consisting of a formyl group, an alkyl group having 1 to 6 carbon atoms and an acyl group having 2 to 6 carbon atoms; R3: a hydrogen atom, a phenyl group, an acetoxymethyl group, a pivaloyloxymethyl group, an ethoxycarbonyl group, a choline group, a dimethylaminoethyl group, a 5-indanyl group, a phthalidinyl group, a 5-alkyl-2-oxo-1,3-dioxol-4-ylmethyl, a 3-acetoxy-2-oxobutyl group, an alkyl group having 1 to 6 carbon atoms, an alkoxymethyl group having 2 to 7 carbon atoms, a phenylalkyl group composed of an alkylene group having 1 to 6 carbon atoms and a phenyl group; and a salt thereof or a hydrate thereof, or an antibacterial agent containing the same as its active ingredient.

  本发明提供了一种对革兰氏阴性菌和革兰氏阳性菌具有较强抗菌活性，且药代动力学优良、安全性高的衍生物和优良药物制剂。 特别是提供了一种由式（I）表示的吡啶并噁嗪衍生物： 其中 R1：氢原子或具有 1 至 6 个碳原子的烷基，其中所述烷基可具有选自羟基、卤素原子、具有 1 至 6 个碳原子的烷硫基和具有 1 至 6 个碳原子的烷氧基的取代基； R2：氢原子或氨基，其中所述氨基可具有一个或两个取代基，这些取代基可从甲酰基、具有 1-6 个碳原子的烷基和具有 2-6 个碳原子的酰基组成的组中选出； R3:氢原子、苯基、乙酰氧甲基、新戊酰氧甲基、乙氧基羰基、胆碱基、二甲基氨基乙基、5-茚满基、酞丁基、5-烷基-2-氧代-1,3-二氧戊环-4-基甲基3-乙酰氧基-2-氧代丁基、具有 1 至 6 个碳原子的烷基、具有 2 至 7 个碳原子的烷氧基甲基、由具有 1 至 6 个碳原子的亚烷基和苯基组成的苯基烷基；及其盐或水合物，或含有相同活性成分的抗菌剂。