*,R^*)>-1-cyclopropyl-7-<3-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-1-oxopropyl>amino>-1-pyrrolidinyl>-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid | 122536-91-8

• 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^*)>-1-cyclopropyl-7-<3-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-1-oxopropyl>amino>-1-pyrrolidinyl>-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid
• 英文别名: (S-(R^*,R^*))-1-cyclopropyl-7-{3-[(2-{[(1,1-dimethylethoxy)carbonyl]amino}-1-oxopropyl)amino]-1-pyrrolidinyl}-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid；7-[(3S)-3-{[N-(tert-Butoxycarbonyl)-L-alanyl]amino}pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid；1-cyclopropyl-6-fluoro-7-[(3S)-3-[[(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]pyrrolidin-1-yl]-4-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 122536-91-8
• 化学式: C₂₄H₃₀FN₅O₆
• 分子量: 503.531
• InChiKey: PNCWJYBQMKGERX-STQMWFEESA-N

物化性质

• 沸点：
  769.3±60.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  141
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  *,R^*)>-1-cyclopropyl-7-<3-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-1-oxopropyl>amino>-1-pyrrolidinyl>-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid 生成 7-[(3S)-3-[[(2S)-2-aminopropanoyl]amino]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Naphthyridine antibacterial agents containing an .alpha.-amino acid in

  摘要：

  本文介绍了具有改善口服和皮下活性的新型喹诺酮和萘啶类抗菌剂，其中这些化合物的7-侧链含有α-氨基酸；还描述了其对应的光学异构体，制备方法以及治疗感染疾病的组合物和方法。

  公开号：

  US04851418A1
• 作为产物：
  描述：

  *,R^*)>-3-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-1-oxopropyl>amino>-1-pyrrolidinecarboxylic acid phenylmethyl ester 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 24.5~25.5 ℃ 、355.77 kPa 条件下， 反应 7.0h， 生成 *,R^*)>-1-cyclopropyl-7-<3-<<2-<<(1,1-dimethylethoxy)carbonyl>amino>-1-oxopropyl>amino>-1-pyrrolidinyl>-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid
  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

• Naphthyridine antibacterial agents containing an .alpha.-amino acid in
  申请人：Warner-Lambert Company

  公开号：US04851418A1

  公开（公告）日：1989-07-25

  Novel quinolone and naphthyridine antibacterial agents are herein described having improved in vivo activity both orally and subcutaneously where the 7-side chain of such compounds contain an .alpha.-amino acid; also described are its corresponding optical isomers, methods of preparation as well as compositions and methods of treating infections diseases.

  本文介绍了具有改善口服和皮下活性的新型喹诺酮和萘啶类抗菌剂，其中这些化合物的7-侧链含有α-氨基酸；还描述了其对应的光学异构体，制备方法以及治疗感染疾病的组合物和方法。
• 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).