(3S,4R)-4-[1-(tert-butoxycarbonylamino)cycloprop-1-yl]-3-fluoro-2-oxo-1-[(S)-1-phenylethyl]pyrrolidine | 215999-30-7

• 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: (3S,4R)-4-[1-(tert-butoxycarbonylamino)cycloprop-1-yl]-3-fluoro-2-oxo-1-[(S)-1-phenylethyl]pyrrolidine
• 英文别名: (3S,4R)-4-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-3-fluoro-2-oxo-1-[(S)-1-phenylethyl]pyrrolidine；4-(R)-(1-tert-butoxycarbonylaminocyclopropyl)-3-(S)-fluoro-1-[1-(S)-phenylethyl]-2-pyrrolidone；tert-butyl N-[1-[(3R,4S)-4-fluoro-5-oxo-1-[(1S)-1-phenylethyl]pyrrolidin-3-yl]cyclopropyl]carbamate
• CAS: 215999-30-7
• 化学式: C₂₀H₂₇FN₂O₃
• 分子量: 362.444
• InChiKey: RVGRLVVRQCEOOP-BPUTZDHNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4R)-4-[1-(tert-butoxycarbonylamino)cycloprop-1-yl]-3-fluoro-2-oxo-1-[(S)-1-phenylethyl]pyrrolidine 在 palladium on activated charcoal N-甲基哌啶 、 盐酸 、 硼烷四氢呋喃络合物 、 水 、 氢气 、 二甲基亚砜 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 190.83h， 生成 5-amino-7-[(3S,4R)-4-(1-aminocycloprop-1-yl)-3-fluoropyrrolidin-1-yl]-6-fluoro-1-[(1R,2S)-2-fluorocycloprop-1-yl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Practical Synthesis of DQ-113, a New Quinolone Antibacterial Agent, by Using the Intramolecular Horner-Wadsworth- Emmons Reaction

  摘要：

  A practical route was developed for synthesizing the C-7 substituent of DQ-113 (6, 5-amino-7-[(3S,4R)-4-(1-aminocycloprop-l-yl)-3-fluoro-pyrrolidin-l-yl]-6-fluoro-l-[(IR,2S)-2-fluorocyclopropan-l-yl]-1,4-dihydro- 8-methyl-4-oxoquinolin-3-carboxylic acid), a new quinolone antibacterial agent for serious infections caused by Gram-positive pathogens. The key step was the intramolecular Homer-Wadsworth-Emmons reaction. In addition, the yield of the final aromatic micleophilic substitution reaction was improved.

  DOI：

  10.3987/com-03-9972
• 作为产物：
  描述：

  ethyl 1-{(3S)-4,4-difluoro-5-oxo-1-[(S)-1-phenylethyl]pyrrolidin-3-yl}cyclopropanecarboxylate 在 sodium hydroxide 、 二苯基膦叠氮化物 、 三乙胺 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 8.0h， 生成 (3S,4R)-4-[1-(tert-butoxycarbonylamino)cycloprop-1-yl]-3-fluoro-2-oxo-1-[(S)-1-phenylethyl]pyrrolidine
  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 ##
• CIS-DISUBSTITUTED AMINOCYCLOALKYL-PYRROLIDINE DERIVATIVES
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1020459A1

  公开（公告）日：2000-07-19

  Antibacterial agents which are excellent in antibacterial activity and safety and comprise compounds represented by general formula (I), their salts, or hydrates of the same, wherein R1 represents hydrogen or alkyl; R2 represents hydrogen or alkyl; R3 and R5 represent each hydrogen; R4 represents hydroxy, halogeno, carbamoyl, alkyl, alkoxy or alkylthio; R6 and R7 represent each hydrogen or alkyl; n is an integer of from 1 to 3; R4 and the substituent on the pyrrolidine ring of general formula (III) are arranged at the cis-configuration; and Q is a partial structure represented by general formula (a).

  具有优异抗菌活性和安全性的抗菌剂，包括通式(I)代表的化合物、它们的盐或它们的水合物，其中 R1 代表氢或烷基；R2 代表氢或烷基；R3 和 R5 各自代表氢；R4 代表羟基、卤素、氨基甲酰基、烷基、烷氧基或烷硫基；R6 和 R7 分别代表氢或烷基；n 为 1 至 3 的整数；R4 和通式（III）中吡咯烷环上的取代基以顺式构型排列；以及 Q 为通式（a）所代表的部分结构。
• US06184388B2
  申请人：——

  公开号：——

  公开（公告）日：——
• 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