HSR-903

• 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: HSR-903
• 英文别名: 5-amino-7-[(7S)-7-amino-5-azaspiro[2.4]hept-5-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid；5-Amino-7-((S)-7-amino-5-azaspiro[2.4]hept-5-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid；5-amino-7-[(7S)-7-amino-5-azaspiro[2.4]hept-5-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylic acid；olamufloxacin；5-amino-7-[(7S)-7-azaniumyl-5-azaspiro[2.4]heptan-5-yl]-1-cyclopropyl-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylate
• 化学式: C₂₀H₂₃FN₄O₃
• 分子量: 386.426
• InChiKey: LEILBPMISZFZQK-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-氨基-1-环丙基-6,7-二氟-1,4-二氢-8-甲基-4-氧代-3-喹啉羧酸 在 盐酸 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 87.08h， 生成 HSR-903
  参考文献：
  名称：

  喹诺酮类抗菌药的研究。V.手性5-氨基-7-（4-取代-3-氨基-1-吡咯烷基）-6-氟-1,4-二氢-8-甲基-4-氧喹啉-3-羧酸的合成及抑菌活性和衍生品。

  摘要：

  我们以前证明了5-氨基-7-（3-氨基-1-吡咯烷基）-1-环丙基-1,4-二氢-8-甲基-4-氧喹啉3-羧酸（7）具有很强的体外抗菌作用甚至可以抵抗喹诺酮类细菌。我们通过引入C-烷基（Me，Et，Pr，di-Me，环丙基）和N-烷基（Me，di-Me）检查了7的3-氨基吡咯烷部分的优化。3-氨基吡咯烷部分的4-位上的C-烷基化增强了体外和体内的抗菌活性。（S）-5-氨基-7-（7-氨基-5-氮杂[2.4]庚-5-基）-1-环丙基-吡咯烷基）-1-环丙基-6-氟-1,4-二氢- 8-甲基-4-氧代喹啉-3-羧酸（15b）具有很强的抗菌活性（包括耐喹诺酮类细菌的体外抗菌活性是环丙沙星（CPFX）的4倍（1）；体内抗菌活性是CPFX（1）的1.5至20倍，并降低了喹诺酮的毒性（在豚鼠中剂量为30 mg / kg时无光毒性（iv）和与4-联苯乙酸并用时会抽搐）大鼠（icv）中以20毫克的剂量服用

  DOI：

  10.1248/cpb.44.1376

文献信息

• 5-amino-8-methyl-7-pyrrolidinylquinoline-3-carboxylic acid derivative
  申请人：Horuriku Seiyaku Co., Ltd.

  公开号：US05547962A1

  公开（公告）日：1996-08-20

  A 5-amino-8-methyl-7-pyrrolidinylquinoline-3-carboxylic acid derivative represented by the general formula: ##STR1## wherein R.sup.1 is a hydrogen atom or a lower alkyl group; R.sup.2 is a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a halogenated lower alkanoyl group or a residue of carboxylic acid ester; R.sup.3 is a hydrogen atom or a lower alkyl group; R.sup.4, R.sup.5 or R.sup.6 are each independently a hydrogen atom or a lower alkyl group; or two of R.sup.4, R.sup.5 and R.sup.6 may be taken together to form a --(CH.sub.2).sub.n -group wherein n is 1 or 2, a stereoisomer thereof, or a pharmacologically acceptable salt thereof, the process for preparing these compounds, a pharmaceutical composition comprising an effective amount of these compounds and methods for the treatment of infectious diseases through the administration to patients of an effective amount of these compounds, and intermediates of these compounds are disclosed. These compounds are effective as antibacterial agents.

  一种由通式表示的5-氨基-8-甲基-7-吡咯啉基喹啉-3-羧酸衍生物：其中R.sup.1是氢原子或低碳基团；R.sup.2是氢原子、低碳基团、低碳酰基团、卤代低碳酰基团或羧酸酯的残基；R.sup.3是氢原子或低碳基团；R.sup.4、R.sup.5或R.sup.6分别独立地是氢原子或低碳基团；或R.sup.4、R.sup.5和R.sup.6中的两个可结合形成一个--(CH.sub.2).sub.n-基团，其中n为1或2，其立体异构体，或其药理学上可接受的盐，揭示了制备这些化合物的方法，包含这些化合物的有效量的药物组合物以及通过向患者给予这些化合物的有效量来治疗传染病的方法，以及这些化合物的中间体。这些化合物作为抗菌剂是有效的。
• Process for producing quinolonecarboxlic acids and intermediates thereof
  申请人：——

  公开号：US20030060631A1

  公开（公告）日：2003-03-27

  This invention relates to methods for the efficient production of quinolonecarboxylic acid based synthetic antibacterial agents which are expected for applications such as excellent medicaments and agricultural chemicals and to intermediate compounds to be used therein. According to the present invention, an amine substituent as the 7-position substituent of the quinolonecarboxylic acid derivative can be efficiently introduced.

  该发明涉及一种高效生产基于喹诺酮羧酸的合成抗菌剂的方法，这些抗菌剂可用于优良的药物和农业化学品等应用，并涉及用于其中的中间化合物。根据本发明，可以有效地引入喹诺酮羧酸衍生物的7位取代基作为胺基取代基。
• Process for producing quinolonecarboxylic acids and intermediates thereof
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US06825353B2

  公开（公告）日：2004-11-30

  This invention relates to methods for the efficient production of quinolonecarboxylic acid based synthetic antibacterial agents which are expected for applications such as excellent medicaments and agricultural chemicals and to intermediate compounds to be used therein. According to the present invention, an amine substituent as the 7-position substituent of the quinolonecarboxylic acid derivative can be efficiently introduced.

  本发明涉及一种高效生产基于喹诺酮羧酸的合成抗菌剂的方法，该抗菌剂可用于优良药物和农业化学品等应用，并涉及其中使用的中间化合物。根据本发明，可以高效地引入喹诺酮羧酸衍生物的7位取代基作为胺取代基。
• 5-Amino-8-methyl-7-pyrrolidinylquinoline-3-carboxylic acid derivative
  申请人：HOKURIKU SEIYAKU CO., LTD.

  公开号：EP0641793A1

  公开（公告）日：1995-03-08

  A 5-amino-8-methyl-7-pyrrolidinylquinoline-3-carboxylic acid derivative represented by the general formula: wherein R¹ is a hydrogen atom or a lower alkyl group; R² is a hydrogen atom, a lower alkyl group, a lower alkanoyl group, a halogenated lower alkanoyl group or a residue of carboxylic acid ester; R³ is a hydrogen atom or a lower alkyl group; R⁴ , R⁵ or R⁶ are each independently a hydrogen atom or a lower alkyl group; or two of R⁴, R⁵ and R⁶ may be taken together to form a -(CH₂) n - group wherein n is 1 or 2, a stereoisomer thereof, or a pharmacologically acceptable salt thereof, the process for preparing these compounds, a pharmaceutical composition comprising an effective amount of these compounds and methods for the treatment of infectious diseases through the administration to patients of an effective amount of these compounds, and intermediates of these compounds are disclosed. These compounds are effective as antibacterial agents.

  由通式代表的 5-氨基-8-甲基-7-吡咯烷基喹啉-3-羧酸衍生物： 其中 R¹ 是氢原子或低级烷基；R² 是氢原子、低级烷基、低级烷酰基、卤代低级烷酰基或羧酸酯残基；R³是氢原子或低级烷基； R⁴、R⁵或 R⁶各自独立地是氢原子或低级烷基；或 R⁴、R⁵和 R⁶中的两个可结合在一起形成-(CH₂) n-基团，其中 n 是 1 或 2、 公开了这些化合物的立体异构体或其药理学上可接受的盐、制备这些化合物的工艺、包含有效量这些化合物的药物组合物和通过向患者施用有效量这些化合物来治疗传染性疾病的方法，以及这些化合物的中间体。 这些化合物是有效的抗菌剂。
• PROCESS FOR PRODUCING QUINOLONECARBOXYLIC ACIDS AND INTERMEDIATES THEREOF
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1258478A1

  公开（公告）日：2002-11-20

  This invention relates to methods for the efficient production of quinolonecarboxylic acid based synthetic antibacterial agents which are expected for applications such as excellent medicaments and agricultural chemicals and to intermediate compounds to be used therein. According to the present invention, an amine substituent as the 7-position substituent of the quinolonecarboxylic acid derivative can be efficiently introduced.

  本发明涉及高效生产喹啉羧酸类合成抗菌剂的方法，这种抗菌剂有望应用于优良的药物和农用化学品等领域，本发明还涉及其中使用的中间化合物。根据本发明，可以有效地引入胺取代基作为喹啉羧酸衍生物的 7 位取代基。