(3R,4S)-7-(3-amino-4-methylpyrrolidinyl)-1-(1,1-dimethylethyl)-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester | 144043-53-8

• 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: (3R,4S)-7-(3-amino-4-methylpyrrolidinyl)-1-(1,1-dimethylethyl)-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester
• 英文别名: ethyl 7-[(3R,4S)-3-amino-4-methylpyrrolidin-1-yl]-1-tert-butyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylate
• CAS: 144043-53-8
• 化学式: C₂₀H₂₇FN₄O₃
• 分子量: 390.458
• InChiKey: PLMPDOGAOPJTLU-NHYWBVRUSA-N

物化性质

• 沸点：
  549.1±50.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  88.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3R,4S)-7-(3-amino-4-methylpyrrolidinyl)-1-(1,1-dimethylethyl)-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester 生成 1,8-Naphthyridine-3-carboxylic acid, 1,4-dihydro-7-(3-amino-4-methyl-1-pyrrolidinyl)-1-(1,1-dimethylethyl)-6-fluoro-4-oxo-, trans-(+-)-, monomethanesulfonate, hydrate
  参考文献：
  名称：

  J. Med. Chem. 1992, 35, 4205-4213

  摘要：

  DOI：
• 作为产物：
  描述：

  (3R,4S)-N-benzyl-3-hydroxy-4-methylpyrrolidine 在 palladium on activated charcoal 吡啶 、 盐酸 、 sodium azide 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 10.0~70.0 ℃ 、101.33 kPa 条件下， 反应 99.17h， 生成 (3R,4S)-7-(3-amino-4-methylpyrrolidinyl)-1-(1,1-dimethylethyl)-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Fluoronaphthyridines and -quinolones as antibacterial agents. 5. Synthesis and antimicrobial activity of chiral 1-tert-butyl-6-fluoro-7-substituted-naphthyridones

  摘要：

  A series of novel 7-substituted-1-tert-butyl-6-fluoronaphthyridone-3-carboxylic acids has been prepared. These derivatives are characterized by chiral aminopyrrolidine substituents at the 7 position. In this paper we report the full details of the asymmetric synthesis of this series of compounds. Structure-activity relationship studies indicate that the absolute stereochemistry at the asymmetric centers of the pyrrolidine ring is critical for maintaining good activity. Compounds 60 and 61 (3-amino-4-methylpyrrolidine enantiomers) were selected for preclinical evaluation.

  DOI：

  10.1021/jm00100a028

文献信息

• Fluoronaphthyridines and quinolones as antibacterial agents. 2. Synthesis and structure-activity relationships of new 1-tert-butyl 7-substituted derivatives
  作者：D. Bouzard、P. Di Cesare、M. Essiz、J. P. Jacquet、J. R. Kiechel、P. Remuzon、A. Weber、T. Oki、M. Masuyoshi

  DOI：10.1021/jm00167a010

  日期：1990.5

  A number of 7-substituted-1-tert-butyl-6-fluoroquinolone-3-carboxylic acids and 7-substituted-1-tert-butyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids have been prepared and tested for antibacterial activities. Among those the 7-aminopyrrolidinyl 20b and the 7-diazabicyclo naphthyridine 18b are the most potent compounds in vitro and in vivo. Physicochemical data and acute toxicity are also discussed

  已经制备了许多7-取代的1-叔丁基-6-氟喹诺酮-3-羧酸和7-取代的1-叔丁基-6-氟-1,8-萘啶-3-羧酸。经测试具有抗菌活性。其中7-氨基吡咯烷基20b和7-二氮杂双环萘啶18b是体外和体内最有效的化合物。还讨论了理化数据和急性毒性。考虑到体外和体内的微生物活性，低毒性和药代动力学特征，化合物18b BMY 40062表现出最有利的总体性能，并被选择用于临床评估。