ethyl 4-hydroxy-6-fluoro-7-(1H-pyrrol-1-yl)quinoline-3-carboxylate | 96623-77-7

• 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
• 英文名称: ethyl 4-hydroxy-6-fluoro-7-(1H-pyrrol-1-yl)quinoline-3-carboxylate
• 英文别名: ethyl 6-fluoro-4-hydroxy-7-(1H-pyrrol-1-yl)quinoline-3-carboxylic acid；ethyl 6-fluoro-7-(pyrrol-1-yl)-4-hydroxyquinoline-3-carboxylate；ethyl 6-fluoro-4-oxo-7-pyrrol-1-yl-1H-quinoline-3-carboxylate
• CAS: 96623-77-7
• 化学式: C₁₆H₁₃FN₂O₃
• 分子量: 300.289
• InChiKey: AZLXODHXSXPORV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-hydroxy-6-fluoro-7-(1H-pyrrol-1-yl)quinoline-3-carboxylate 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 伊洛沙星
  参考文献：
  名称：

  Stefancich; Artico; Corelli, Farmaco, Edizione Scientifica, 1985, vol. 40, # 4, p. 237 - 248

  摘要：

  DOI：
• 作为产物：
  描述：

  1-(2-氟-5-硝基苯基)-1H-吡咯 在 Rh/Al₂O₃ 氢气 作用下， 以 二苯醚 、 乙醇 为溶剂， 反应 0.5h， 生成 ethyl 4-hydroxy-6-fluoro-7-(1H-pyrrol-1-yl)quinoline-3-carboxylate
  参考文献：
  名称：

  Stefancich; Artico; Corelli, Farmaco, Edizione Scientifica, 1985, vol. 40, # 4, p. 237 - 248

  摘要：

  DOI：

文献信息

• 1-substituted derivatives of
  申请人：Provesan S.A.

  公开号：US04727080A1

  公开（公告）日：1988-02-23

  The present invention relates to new 1-substituted derivatives of 6-fluoro-7-(pyrrol-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, their preparation and their application as drugs. The 1-substituted derivatives of 6-fluoro-7-(pyrrol-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid according to the invention correspond to the general formula I: ##STR1## in which: R represents a methyl radical, a 2-hydroxyethyl radical, a vinyl radical, a cyclopropylmethyl radical, a propyl radical, a cyclopropyl radical, a 2-fluoroethyl radical, a methylamino radical or an ethylamino radical, as well as their physiologically acceptable alkali metal or alkaline earth metal salts. They are useful as antimicrobial agents, in particular as antibacterial and fungistatic agents.

  本发明涉及6-氟-7-(吡咯-1-基)-1,4-二氢-4-氧喹啉-3-羧酸的新1-取代衍生物，其制备以及作为药物的应用。根据本发明，6-氟-7-(吡咯-1-基)-1,4-二氢-4-氧喹啉-3-羧酸的1-取代衍生物符合一般式I：##STR1## 其中：R代表甲基基团、2-羟乙基基团、乙烯基基团、环丙基甲基基团、丙基基团、环丙基基团、2-氟乙基基团、甲氨基基团或乙氨基基团，以及它们的生理上可接受的碱金属或碱土金属盐。它们可用作抗微生物剂，特别是作为抗菌和真菌静菌剂。
• 1-Ethyl-6-fluoro-7-(1H-pirrol-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid: preparation and antimicrobial activities
  申请人：BIOCHEM DESIGN S.r.l.

  公开号：EP0155244A2

  公开（公告）日：1985-09-18

  The title compound 1-ethyl-6-fluoro-7-(1-pyrrol-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid is a quinolone carboxylic acid derivative of "oxacin" family bearing a fluorine atom and a pyrrol-1-yl moiety at 6 and 7 position respectively. It is represented by the following formula: and has been prepared by alkaline hydrolysis of the corresponding ethyl ester. The latter compound has been synthesized starting from 2-fluoro-5-nitroaniline. Treatment of this amine with diethoxytetrahydrofuran in glacial acetic acid afforded 4-fluoro-3-(1-H-pyrrol-1-yl)-nitrobenzene, which was then reduced by catalytic hydrogenation to 4-fluoro-3-(1 H-pyrrol-1-yl)aniline. Reaction of this compound with diethyl ethoxymethylene malonate and cyclization of the malonate obtained by heating in diphenyl ether at 120°C resulted in formation of ethyl ester of 6-fluoro-7-(1H-pyrrol-1-yl)quinoline-3-carboxylic acid. Ethylation of this ester with ethyl iodide in the presence of sodium carbonate gave the required 1-ethyl-6-fluoro-7-(1H-pyrrol-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester. The title acid exhibits high activity against Gram-positive bacteria, Enterobacteriaceae, Proteus and Pseudomonas, superior to those of nalidixic acid, piromidic acid and pipemidic acid; again, its antimicrobial spectrum is somewhat superior also to that of enoxacin. 1-Ethyl-6-fluoro-7-(1H-pyrrol-1-yl)-1,4-dihydro-4-oxo- quinoline-3-carboxylic acid is a new potent fluorinated quinolone antibacterial agent useful in the management of urinary tract and systemic infections. The present invention also relates to a process for the preparation of such compound.

  标题化合物 1-乙基-6-氟-7-(1-吡咯-1-基)-1,4-二氢-4-氧代喹啉-3-羧酸是一种 "氧杂喹啉 "家族的喹啉酮羧酸衍生物，其 6 位和 7 位分别含有一个氟原子和一个吡咯-1-基分子。其分子式如下 并通过碱水解相应的乙酯制备而成。后一种化合物是从 2-氟-5-硝基苯胺开始合成的。用冰醋酸中的二乙氧基四氢呋喃处理这种胺，可得到 4-氟-3-(1-H-吡咯-1-基)-硝基苯，然后通过催化氢化还原成 4-氟-3-(1-H-吡咯-1-基)苯胺。 将这种化合物与乙氧基亚甲基丙二酸二乙酯反应，并在 120°C 的二苯醚中加热使丙二酸二乙酯环化，生成 6-氟-7-(1H-吡咯-1-基)喹啉-3-羧酸乙酯。在碳酸钠存在下，用碘化乙酯对该酯进行乙酯化反应，得到了所需的 1-乙基-6-氟-7-(1H-吡咯-1-基)-1,4-二氢-4-氧代喹啉-3-羧酸乙酯。 标题酸对革兰氏阳性菌、肠杆菌科、变形杆菌和假单胞菌具有较高的活性，优于萘啶酸、吡咯咪啶酸和哌啶咪啶酸；其抗菌谱也略优于恩诺沙星。 1-乙基-6-氟-7-(1H-吡咯-1-基)-1,4-二氢-4-氧代-喹啉-3-羧酸是一种新型强效氟化喹诺酮类抗菌剂，可用于治疗尿路感染和全身感染。 本发明还涉及一种制备这种化合物的工艺。
• Massa; Corelli; Mai, Il Farmaco, 1989, vol. 44, # 9, p. 779 - 793
  作者：Massa、Corelli、Mai、Artico、Panico、Simonetti

  DOI：——

  日期：——
• Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 2. Synthesis and Structure−Activity Relationship of Potent and Selective Cannabinoid-2 Receptor Agonists Endowed with Analgesic Activity in Vivo
  作者：Serena Pasquini、Lorenzo Botta、Teresa Semeraro、Claudia Mugnaini、Alessia Ligresti、Enza Palazzo、Sabatino Maione、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1021/jm800552f

  日期：2008.8.1

  Quinolone-3-carboxamides 11 bearing at position 5, 6, 7, or 8 diverse substituents such as halides, alkyl, aryl, alkoxy, and aryloxy groups differing in their steric/electronic properties, were prepared. The new compounds were tested in vitro for CB1 and CB2 receptor affinity in comparison with the reference compounds rimonabant and SR144528. The tested compounds exhibited CB2 affinity in the ran, e from 55.9 to 0.8 nM and CB1 affinity in the range from > 10 000 to 5.3 nM, with selectivity indeces [K-i(CB1)/K-i(CB2)] varying from > 2666.6 to 1.23. On the basis of the structure-selectivity relationship developed, the presence of a substituent at C6/C8 or C7 well accounts for the high or low CB2 selectivity, respectively. Compound 11c, characterized by high CB2 affinity and selectivity, showed analgesic activity in the formalin test of acute peripheral and inflammatory pain in mice as a result of selective CB2 agonistic activity.
• MASSA, S.;CORELLI, F.;MAI, A.;ARTICO, M.;PANICO, S.;SIMONETTI, N., FARMACO, 44,(1989) N, C. 779-793
  作者：MASSA, S.、CORELLI, F.、MAI, A.、ARTICO, M.、PANICO, S.、SIMONETTI, N.

  DOI：——

  日期：——