(3R)-3-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-5-oxo-1-[(S)-1-phenylethyl]pyrrolidine | 431058-50-3

• 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)-3-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-5-oxo-1-[(S)-1-phenylethyl]pyrrolidine
• 英文别名: 4-(R)-[1-(tert-butoxycarbonylamino)cyclopropyl]-1-[1-(S)-phenylethyl]pyrrolidin-2-one；tert-butyl N-[1-[(3R)-5-oxo-1-[(1S)-1-phenylethyl]pyrrolidin-3-yl]cyclopropyl]carbamate
• CAS: 431058-50-3
• 化学式: C₂₀H₂₈N₂O₃
• 分子量: 344.454
• InChiKey: BDLXLRIOJUVBQP-GOEBONIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 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：
  3

反应信息

• 作为反应物：
  描述：

  (3R)-3-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-5-oxo-1-[(S)-1-phenylethyl]pyrrolidine 在 钯 盐酸 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 生成 7-[3-(R)-(1-aminocyclopropyl)pyrrolidin-1-yl]-1-cyclopropyl-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  DEHALOGENO COMPOUNDS

  摘要：

  公开号：

  EP1336611B1
• 作为产物：
  描述：

  叔丁醇 、 1-{(3S)-5-oxo-1-[(S)-1-phenylethyl]pyrrolidin-3-yl}cyclopropanecarboxylic acid 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 17.5h， 以90%的产率得到(3R)-3-[1-(tert-butoxycarbonylamino)cyclopropan-1-yl]-5-oxo-1-[(S)-1-phenylethyl]pyrrolidine
  参考文献：
  名称：

  Design, synthesis and biological evaluations of novel 7-[3-(1-aminocycloalkyl)pyrrolidin-1-yl]-6-desfluoro-8-methoxyquinolones with potent antibacterial activity against multi-drug resistant Gram-positive bacteria

  摘要：

  A series of novel 6-desfluoro [des-F(6)] and 6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-8-methoxyquinolones bearing 3-(1-aminocycloalkyl)pyrrolidin-1-yl substituents at the C-7 position (1-6) was synthesized to obtain potent drugs for nosocomial infections caused by Gram-positive pathogens. The des-F(6) compounds 4-6 exhibited at least four times more potent activity against representative Gram-positive bacteria than ciprofloxacin or moxifloxacin. Among the derivatives, 7-[(3R)-3-(1-aminocyclopropan-1-yl)pyrrolidin-1-yl] derivative 4, which showed favorable profiles in preliminary toxicological and non-clinical pharmacokinetic studies, exhibited potent antibacterial activity against clinically isolated Gram-positive pathogens that had become resistant to one or more antibiotics. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.026

文献信息

• Dehalogeno compounds
  申请人：——

  公开号：US20040063754A1

  公开（公告）日：2004-04-01

  3-(1-Aminocycloalkyl)pyrrolidinyl-substituted-6-dehalodeno(hydrogen-substituted)quinolon carboxylic acid derivatives having specific substitunets as represented by the following formula (I), its salts, and hydrates thereof exhibit a broad and potent antibacterial activity on gram-negative and gram-positive bacteria, in particular, resistant bacteria typified by gram-positive cocci, including MRSA, PRSP and VRE. Thus these compounds are usable as drugs. 1

  具有特定取代基的3-(1-氨基环烷基)吡咯烷基取代的6-去卤代(氢取代)喹诺酮羧酸衍生物及其盐和水合物，如下式(I)所示，表现出广谱和强效的抗菌活性，对革兰氏阴性菌和革兰氏阳性菌均有效，特别是对革兰氏阳性球菌等耐药菌，包括MRSA、PRSP和VRE有良好的抗菌活性。因此这些化合物可用作药物。
• Dehalogeno-compounds
  申请人：Takahashi Hisashi

  公开号：US20070123560A1

  公开（公告）日：2007-05-31

  3-(1-Aminocycloalkyl)pyrrolidinyl-substituted-6-dehalodeno(hydrogen-substituted)quinolon carboxylic acid derivatives having specific substituents as represented by the following formula (I), its salts, and hydrates thereof exhibit a broad and potent antibacterial activity on gram-negative and gram-positive bacteria, in particular, resistant bacteria typified by gram-positive cocci, including MRSA, PRSP and VRE. Thus these compounds are usable as drugs.

  具有特定取代基的3-(1-氨基环烷基)吡咯烷基取代的6-去卤代（氢取代）喹诺酮羧酸衍生物，其盐和水合物，如以下公式（I）所示，表现出广谱和强效的抗菌活性，对革兰氏阴性和革兰氏阳性细菌均有效，特别是对革兰氏阳性球菌等耐药菌，包括MRSA、PRSP和VRE。因此，这些化合物可用作药物。
• Exploration of the Activity of 7-Pyrrolidino-8-methoxyisothiazoloquinolones against Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA)
  作者：Ha Young Kim、Jason A. Wiles、Qiuping Wang、Godwin C. G. Pais、Edlaine Lucien、Akihiro Hashimoto、David M. Nelson、Jane A. Thanassi、Steven D. Podos、Milind Deshpande、Michael J. Pucci、Barton J. Bradbury

  DOI：10.1021/jm101604v

  日期：2011.5.12

  A series of 7-(3'-substituted)pyrrolidino-8-methoxyisothiazoloquinolone (ITQ) analogues were prepared, and their antibacterial potency against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli were compared. Many of these analogues had MIC <= 0.25 mu g/mL against quinolone-resistant MRSA strains. The stereochemical preference was explored for a series of 1 ''-methyl-3'-aminomethylpyrrolidine analogues. Antibacterial activity was generally more favorable with 3'-R, 1 ''-S configuration. Substitution on the 3'-aminomethyl nitrogen tended to decrease activity, while potency was maintained with disubstitution or aryl substitution at the 1 ''-carbon. The 7-[(R)-3-((S)-1-aminoethyl)pyrrolidin-1-yl] analogue (6a(R,S)) and the (R)-7-[3-(2-aminopropan-2-yl)pyrrolidin-1-yl] analogue (7a(R)) were found to be the ITQs with the most promising antibacterial profiles. The MICs of these select ITQs versus a panel of clinical MRSA strains were determined, and the ITQs were found to have 8- to 16-fold greater potency than linezolid. These analogues were also evaluated for inhibition of the target enzymes, topoisomerase IV and DNA gyrase, from both wild-type and multidrug resistant strains. The ITQs were up to >30 times more inhibitory against these targets than the fluoroquinolone moxifloxacin.
• US7902226B2
  申请人：——

  公开号：US7902226B2

  公开（公告）日：2011-03-08
• DEHALOGENO COMPOUNDS
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1336611B1

  公开（公告）日：2007-09-05