(3R,4R)-1-benzyloxycarbonyl-4-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-3-fluoropyrrolidine | 190954-36-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R,4R)-1-benzyloxycarbonyl-4-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-3-fluoropyrrolidine
• 英文别名: 1-Benzyloxycarbonyl-4-(r)-(1-tert-butoxycarbonylaminocyclopropyl)-3-(r)-fluoropyrrolidine；benzyl (3R,4R)-3-fluoro-4-[1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropyl]pyrrolidine-1-carboxylate
• CAS: 190954-36-0
• 化学式: C₂₀H₂₇FN₂O₄
• 分子量: 378.444
• InChiKey: REQCUNOUXLIOGS-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,4R)-1-benzyloxycarbonyl-4-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-3-fluoropyrrolidine 在 5percent Pd/C 水 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 20.0~120.0 ℃ 、441.31 kPa 条件下， 反应 103.0h， 生成 5-Amino-7-[(3R,4R)-3-(1-tert-butoxycarbonylamino-cyclopropyl)-4-fluoro-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 3-(1-ethoxycarbonylcyclopropan-1-yl)-3-hydroxybutanoate 在 platinum(IV) oxide 劳森试剂 、 吡啶 、 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 偶氮二异丁腈 、 Raney Ni W-6 、 二苯基膦叠氮化物 、 氢气 、 碳酸氢钠 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 乙醇 、 正己烷 、 二氯甲烷 、 苯 为溶剂， 反应 68.0h， 生成 (3R,4R)-1-benzyloxycarbonyl-4-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-3-fluoropyrrolidine
  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

• Substituted aminocycloalkylpyrrolidine derivatives and cis-substituted
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US06121285A1

  公开（公告）日：2000-09-19

  An antimicrobial drug having excellent antimicrobial activity and high safety is disclosed, which comprises as an active ingredient, a quinolone-derivative having a substituted aminocycloalkylpyrrolidine as a substituent and which is further substituted with various substituents, represented by formula (I), its salts and hydrates thereof: ##STR1## wherein Q is represented by formula (II) or (IV). ##STR2## Also disclosed is a quinolone derivative where R.sup.4 and the substituent on the pyrrolidine ring of the following formula: ##STR3## are located at the cis-configuration; and Q is represented by the formula: ##STR4##

  本发明涉及一种具有优异的抗微生物活性和高安全性的抗微生物药物，其包括一种活性成分，即具有取代的氨基环烷基吡咯烷基取代基的喹诺酮衍生物，进一步取代各种取代基，由式(I)表示，其盐和水合物： ## STR1 ## 其中Q由式(II)或(IV)表示。 ## STR2 ## 还公开了一种喹诺酮衍生物，其中R.sup.4和以下公式的吡咯烷环上的取代基： ## STR3 ## 位于顺式构型; Q由以下公式表示： ## STR4 ##
• US06184388B2
  申请人：——

  公开号：——

  公开（公告）日：——
• SUBSTITUTED AMINOCYCLOALKYLPYRROLIDINE DERIVATIVES
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0911328B1

  公开（公告）日：2006-02-08
• US6121285A
  申请人：——

  公开号：US6121285A

  公开（公告）日：2000-09-19
• US6184388B1
  申请人：——

  公开号：US6184388B1

  公开（公告）日：2001-02-06