1-环丙基-6-氟-7-((4-异丙基噻唑-2-基)甲氧基)-4-氧代-1,4-二氢喹啉-3-羧酸乙酯 | 422280-23-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 1-环丙基-6-氟-7-((4-异丙基噻唑-2-基)甲氧基)-4-氧代-1,4-二氢喹啉-3-羧酸乙酯
• 英文名称: ethyl 1-cyclopropyl-6-fluoro-7-[(4-isopropyl-1,3-thiazol-2-yl)methoxy]-4-oxo-1,4-dihydro-3-quinolinecarboxylate
• 英文别名: Ethyl 1-cyclopropyl-6-fluoro-4-oxo-7-[(4-propan-2-yl-1,3-thiazol-2-yl)methoxy]quinoline-3-carboxylate
• CAS: 422280-23-7
• 化学式: C₂₂H₂₃FN₂O₄S
• 分子量: 430.5
• InChiKey: FEBWODAGJPJNAD-UHFFFAOYSA-N

物化性质

• 沸点：
  584.8±50.0 °C(Predicted)
• 密度：
  1.354±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  97
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-环丙基-6-氟-7-((4-异丙基噻唑-2-基)甲氧基)-4-氧代-1,4-二氢喹啉-3-羧酸乙酯 在 盐酸 、 溶剂黄146 作用下， 以100%的产率得到1-Cyclopropyl-6-fluoro-7-(4-isopropyl-thiazol-2-ylmethoxy)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 2: achieving activity in vivo through the use of alternative scaffolds

  摘要：

  Problems of low solubility, high serum protein binding, and lack of efficacy in vivo in first generation MexAB-OprM specific efflux pump inhibitors were addressed. Through the use of pharmacophore modelling, the key structural elements for pump inhibition were defined. Use of alternative scaffolds upon which the key elements were arrayed gave second generation leads with greatly improved physical properties and activity in the potentiation of antibacterial quinolones (levofloxacin and sitafloxacin) versus Pseudomonas aeruginosa in vivo. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.07.027
• 作为产物：
  描述：

  1-环丙基-6,7-二氟-4-氧代-1,4-二氢喹啉-3-羧酸乙酯 、 (4-异丙基噻唑-2-基)甲醇 在 18-冠醚-6 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到1-环丙基-6-氟-7-((4-异丙基噻唑-2-基)甲氧基)-4-氧代-1,4-二氢喹啉-3-羧酸乙酯
  参考文献：
  名称：

  MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 2: achieving activity in vivo through the use of alternative scaffolds

  摘要：

  Problems of low solubility, high serum protein binding, and lack of efficacy in vivo in first generation MexAB-OprM specific efflux pump inhibitors were addressed. Through the use of pharmacophore modelling, the key structural elements for pump inhibition were defined. Use of alternative scaffolds upon which the key elements were arrayed gave second generation leads with greatly improved physical properties and activity in the potentiation of antibacterial quinolones (levofloxacin and sitafloxacin) versus Pseudomonas aeruginosa in vivo. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.07.027

文献信息

• Drug efflux pump inhibitor
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1652839A2

  公开（公告）日：2006-05-03

  A medicament for preventive and/or therapeutic treatment of a microbial infection having an activity of eliminating resistance of a microorganism with acquired resistance to an antimicrobial agent, which comprises as an active ingredient a compound represented by the following general formula (I), a physiologically acceptable salt thereof, or a hydrate thereof: wherein R1 and R2 independently represent hydrogen atom, a halogen atom, carboxyl group and the like; J1 represents a 5- or 6-membered heteroaromatic ring; W1 represents -CH=CH-, -C≡C-, -CH2CH2- and the like; A1 represents phenylene group, pyridinediyl group, furandiyl group and the like; G1 represents oxygen atom, carbonyl group, ethynyl group and the like; p represents an integer of from 0 to 3; G2 represents phenylene group, furandiyl group, tetrahydrofurandiyl group and the like; G3 represents -CH2- or single bond; m and n represent an integer of 0 or 1; and Q1 represents an acidic group.

  一种用于预防和/或治疗微生物感染的药物，具有消除对抗菌剂产生抗药性的微生物的抗药性的活性，其活性成分包括下式（I）所代表的化合物、其生理上可接受的盐或其水合物： 其中 R1 和 R2 分别代表氢原子、卤素原子、羧基等；J1 代表 5 或 6 元杂芳环；W1 代表 -CH=CH-、-C≡C-、-CH2CH2- 等；A1 代表亚苯基、吡啶二基、呋喃二基等；G1 代表氧原子、羰基、乙炔基等；p 代表 0 至 3 的整数；G2 代表亚苯基、呋喃二基、四氢呋喃二基等；G3 代表 -CH2- 或单键；m 和 n 代表 0 或 1 的整数；以及 Q1 代表酸性基团。
• DRUG DISCHARGE PUMP INHIBITORS
  申请人：Trine Pharmaceuticals, Inc.

  公开号：EP1227084B1

  公开（公告）日：2005-12-14
• MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 2: achieving activity in vivo through the use of alternative scaffolds
  作者：Kiyoshi Nakayama、Yohei Ishida、Masami Ohtsuka、Haruko Kawato、Ken-ichi Yoshida、Yoshihiro Yokomizo、Toshiharu Ohta、Kazuki Hoshino、Tsuyoshi Otani、Yuichi Kurosaka、Kumi Yoshida、Hiroko Ishida、Ving J. Lee、Thomas E. Renau、William J. Watkins

  DOI：10.1016/j.bmcl.2003.07.027

  日期：2003.12

  Problems of low solubility, high serum protein binding, and lack of efficacy in vivo in first generation MexAB-OprM specific efflux pump inhibitors were addressed. Through the use of pharmacophore modelling, the key structural elements for pump inhibition were defined. Use of alternative scaffolds upon which the key elements were arrayed gave second generation leads with greatly improved physical properties and activity in the potentiation of antibacterial quinolones (levofloxacin and sitafloxacin) versus Pseudomonas aeruginosa in vivo. (C) 2003 Elsevier Ltd. All rights reserved.