| 1297434-62-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• CAS: 1297434-62-8
• 化学式: C₁₄H₂₂N₂
• 分子量: 218.342
• InChiKey: MRWADXJLYWZRTH-VBVNFKHJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.42
• 重原子数：
  16.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  29.26
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  在 20% palladium(II) hydroxide on carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 反应 33.0h， 生成 (R)-9-cyclopropyl-6-fluoro-7-{3-[1-(isopropylamino)ethyl]pyrrolidin-1-yl}-8-methoxyisothiazolo[5,4-b]quinoline-3,4(2H,9H)-dione
  参考文献：
  名称：

  Exploration of the Activity of 7-Pyrrolidino-8-methoxyisothiazoloquinolones against Methicillin-Resistant Staphylococcus aureus (MRSA)

  摘要：

  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.

  DOI：

  10.1021/jm101604v