7-[(R)-3-((S)-2-Amino-propionylamino)-pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid; hydrochloride | 122536-42-9

• 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: 7-[(R)-3-((S)-2-Amino-propionylamino)-pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid; hydrochloride
• CAS: 122536-42-9
• 化学式: C₁₉H₂₂FN₅O₄*ClH
• 分子量: 439.874
• InChiKey: YUOPUVABKXFBTF-BAUSSPIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.03
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  130.55
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  (S-(R*,R*))-3-((2-(((1,1-dimethylethoxy)carbonyl)amino)-1-oxopropyl)amino)-1-pyrrolidinecarboxylic acid phenylmethyl ester 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 24.5~25.5 ℃ 、355.77 kPa 条件下， 反应 10.0h， 生成 7-[(R)-3-((S)-2-Amino-propionylamino)-pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-[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