[1-((R)-4,4-Difluoro-pyrrolidin-3-yl)-cyclopropyl]-carbamic acid tert-butyl ester | 1027185-18-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: [1-((R)-4,4-Difluoro-pyrrolidin-3-yl)-cyclopropyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[1-[(3R)-4,4-difluoropyrrolidin-3-yl]cyclopropyl]carbamate
• CAS: 1027185-18-7
• 化学式: C₁₂H₂₀F₂N₂O₂
• 分子量: 262.3
• InChiKey: QZRDSXPTNNGYAV-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [1-((R)-4,4-Difluoro-pyrrolidin-3-yl)-cyclopropyl]-carbamic acid tert-butyl ester 在 盐酸 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.25h， 生成 5-Amino-7-[(R)-4-(1-amino-cyclopropyl)-3,3-difluoro-pyrrolidin-1-yl]-6-fluoro-1-((1R,2S)-2-fluoro-cyclopropyl)-8-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 5-Amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolonecarboxylic Acid Antibacterials Having Fluorinated 7-[(3R)-3-(1-Aminocyclopropan-1-yl)pyrrolidin-1-yl] Substituents

  摘要：

  A series of novel 5-amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolones bearing fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl substituents at the C-7 position (2-4) was synthesized to obtain potent drugs for infections caused by Gram-positive pathogens, which include resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). These fluorinated compounds 2-4 exhibited potent antibacterial activity comparable with that of a compound bearing a non-fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidine moiety at the C-7 position (1) and had at least 4 times more potent activity against representative Gram-positive bacteria than ciprofloxacin (CPFX), gatifloxacin (GFLX), or moxifloxacin (MFLX). Among them, the 7-[(3S,4R)-4-(1-aminocyclopropan-1-yl)-3-fluoropyr-rolidin-1-yl] derivative 3 (=DQ-113), which showed favorable profiles in preliminary toxicological and nonclinical pharmcokinetic studies, exhibited potent antibacterial activity against clinically isolated resistant Gram-positive pathogens.

  DOI：

  10.1021/jm020328y
• 作为产物：
  描述：

  ethyl 1-{(3S)-4,4-difluoro-1-[(S)-1-phenylethyl]-5-thioxopyrrolidin-3-yl}cyclopropanecarboxylate 在 5percent Pd/C sodium hydroxide 、 Raney Ni W-6 、 二苯基膦叠氮化物 、 水 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 [1-((R)-4,4-Difluoro-pyrrolidin-3-yl)-cyclopropyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 5-Amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolonecarboxylic Acid Antibacterials Having Fluorinated 7-[(3R)-3-(1-Aminocyclopropan-1-yl)pyrrolidin-1-yl] Substituents

  摘要：

  A series of novel 5-amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolones bearing fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl substituents at the C-7 position (2-4) was synthesized to obtain potent drugs for infections caused by Gram-positive pathogens, which include resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). These fluorinated compounds 2-4 exhibited potent antibacterial activity comparable with that of a compound bearing a non-fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidine moiety at the C-7 position (1) and had at least 4 times more potent activity against representative Gram-positive bacteria than ciprofloxacin (CPFX), gatifloxacin (GFLX), or moxifloxacin (MFLX). Among them, the 7-[(3S,4R)-4-(1-aminocyclopropan-1-yl)-3-fluoropyr-rolidin-1-yl] derivative 3 (=DQ-113), which showed favorable profiles in preliminary toxicological and nonclinical pharmcokinetic studies, exhibited potent antibacterial activity against clinically isolated resistant Gram-positive pathogens.

  DOI：

  10.1021/jm020328y

文献信息

• Synthesis and Structure−Activity Relationships of 5-Amino-6-fluoro-1-[(1<i>R</i>,2<i>S</i>)-2-fluorocyclopropan-1-yl]-8-methylquinolonecarboxylic Acid Antibacterials Having Fluorinated 7-[(3<i>R</i>)-3-(1-Aminocyclopropan-1-yl)pyrrolidin-1-yl] Substituents
  作者：Hiroaki Inagaki、Satoru Miyauchi、Rie N. Miyauchi、Haruko C. Kawato、Hitoshi Ohki、Norikazu Matsuhashi、Katsuhiro Kawakami、Hisashi Takahashi、Makoto Takemura

  DOI：10.1021/jm020328y

  日期：2003.3.1

  A series of novel 5-amino-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methylquinolones bearing fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl substituents at the C-7 position (2-4) was synthesized to obtain potent drugs for infections caused by Gram-positive pathogens, which include resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci (VRE). These fluorinated compounds 2-4 exhibited potent antibacterial activity comparable with that of a compound bearing a non-fluorinated (3R)-3-(1-aminocyclopropan-1-yl)pyrrolidine moiety at the C-7 position (1) and had at least 4 times more potent activity against representative Gram-positive bacteria than ciprofloxacin (CPFX), gatifloxacin (GFLX), or moxifloxacin (MFLX). Among them, the 7-[(3S,4R)-4-(1-aminocyclopropan-1-yl)-3-fluoropyr-rolidin-1-yl] derivative 3 (=DQ-113), which showed favorable profiles in preliminary toxicological and nonclinical pharmcokinetic studies, exhibited potent antibacterial activity against clinically isolated resistant Gram-positive pathogens.