*,R^*)>-7-<3-<(2-amino-1-oxopropyl)amino>-1-pyrrolidinyl>-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride | 122536-48-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: *,R^*)>-7-<3-<(2-amino-1-oxopropyl)amino>-1-pyrrolidinyl>-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride
• 英文别名: (S-(R^*,R^*))-7-{3-[(2-amino-1-oxopropyl)amino]-1-pyrrolidinyl}-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride；7-[(3S)-3-[[(2S)-2-aminopropanoyl]amino]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid;hydrochloride
• CAS: 122536-48-5
• 化学式: C₁₉H₂₂FN₅O₄*ClH
• 分子量: 439.874
• InChiKey: YUOPUVABKXFBTF-IYPAPVHQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.03
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  环丙基萘啶羧酸 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 7.0h， 生成 *,R^*)>-7-<3-<(2-amino-1-oxopropyl)amino>-1-pyrrolidinyl>-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride
  参考文献：
  名称：

  Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity

  摘要：

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

  DOI：

  10.1021/jm00088a011

文献信息

• Quinolone and naphthyridine antibacterial agents containing an alpha-amino acid in the side chain of the 7-substituent
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0304087A2

  公开（公告）日：1989-02-22

  Novel quinolone and naphthyridine antibacterial agents of the formula I are herein described having improved in vivo activity both orally and subcutaneously where the 7-side chain of such compounds contain an a-amino acid; also described are its corresponding optical isomers, methods of preparation as well as pharmaceutical useful intreating infectious diseases.

  本文描述了式 I 的新型喹诺酮类和萘啶类抗菌剂，其口服和皮下注射活性均有所提高。 所述的新型喹诺酮类和萘啶类抗菌剂具有更好的口服和皮下注射活性，其中此类化合物的 7 侧链含有 a-氨基酸；还描述了其相应的光学异构体、制备方法以及治疗传染性疾病的药物用途。
• SOLUBLE CALCIUM LACTATE/QUINDONECARBOXYLIC ACIDS COMPLEXES AS NON-IRRITATING PARENTERAL FORMS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0666743B1

  公开（公告）日：1998-12-02
• US4851418A
  申请人：——

  公开号：US4851418A

  公开（公告）日：1989-07-25
• US5290794A
  申请人：——

  公开号：US5290794A

  公开（公告）日：1994-03-01
• Quinolone antibacterial agents. Synthesis and structure-activity relationships of a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo pseudomonas activity
  作者：Joseph P. Sanchez、John M. Domagala、Carl L. Heifetz、Stephen R. Priebe、Josephine A. Sesnie、Ashok K. Trehan

  DOI：10.1021/jm00088a011

  日期：1992.5

  A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparatively solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).