- 1-cyclopropyl-4-oxo-7-fluoro-8-methoxy -1,4-dihydro-quinoline-3-carboxylic acid synthesizing method
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The invention discloses a synthesis method of 1-cyclopropyl-4-oxo-7-fluoro-8-methoxy-1,4-dihydroquinolyl-3-carboxylic acid. The synthesis method comprises the following reaction steps: reacting m-difluorophenyl with an organolithium reagent, reacting an obtained aryllithium intermediate with borate, quenching to obtain 2,6-difluorophenylboronic acid and 2,6-difluorophenylborate, reacting 2,6-difluorophenol obtained through oxidation with a methylating reagent, reacting the obtained 2,6-difluorophenylmethyl ether with the organolithium reagent, reacting the obtained corresponding aryllithium intermediate with carbon dioxide, reacting the obtained product with an acylchlorinating reagent to obtain 2,4-difluoro-3-methoxy benzoyl chloride, and performing cyclization, hydrolysis and the like to obtain the 1-cyclopropyl-4-oxo-7-fluoro-8-methoxy-1,4-dihydroquinolyl-3-carboxylic acid. The synthesis method has the advantages as follows: raw materials are easy to obtain; the yield in each step is high; the atom economy is high; the synthesis method is suitable for industrial application.
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Paragraph 0023; 0098; 0099
(2017/01/26)
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- Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen activator inhibitor-1 (PAI-1)
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Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as possible treatments for a range of conditions, including atherosclerosis, venous thrombosis, and obesity. We describe the synthesis and inhibitory activity of a novel series
- El-Ayache, Nadine C.,Li, Shih-Hon,Warnock, Mark,Lawrence, Daniel A.,Emal, Cory D.
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supporting information; experimental part
p. 966 - 970
(2010/06/16)
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- HETEROCYCLICALLY SUBSTITUTED PENTANOL DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, AND USE THEREOF AS ANTI-INFLAMMATORY AGENTS
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The invention relates to pentanol derivatives of general formula (I), which are substituted by quinazoline, quinoxaline, cinnoline, indazole, phthalazine, naphthyridine, benzothiazole, dihydroindolone, dihydroisoindolone, benzimidazole, or indole, a method for the production thereof, and the use thereof as anti-inflammatory agents.
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Page/Page column 45-50
(2010/02/10)
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- 1-AMINO-2-OXY-SUBSTITUTED TETRAHYDRONAPHTALENE DERIVATIVES, METHODS FOR THE PRODUCTION THEREOF, AND THEIR USE AS ANTIPHLOGISTICS
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The invention relates to polysubstituted tetrahydronaphtalene derivatives of formula (I), to methods for the production thereof, and to their use as antiphlogistics. The substituents are defined in Claim 1.
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Page/Page column 59
(2010/02/11)
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- Quinolonecarboxylic acid derivatives or salts thereof
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PCT No. PCT/JP97/00317 Sec. 371 Date Aug. 10, 1998 Sec. 102(e) Date Aug. 10, 1998 PCT Filed Feb. 7, 1997 PCT Pub. No. WO97/29102 PCT Pub. Date Aug. 14, 1997The present invention relates to a quinolone-carboxylic acid derivative represented by the general
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- The effect of fluorine substitution on the physicochemical properties and the analgesic activity of paracetamol
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The physicochemical properties and analgesic action of six fluorinated analogues of 4-hydroxyacetanilide (paracetamol) have been investigated. Fluorine substitution adjacent to the hydroxyl group increased lipophilicity and oxidation potential whilst substitution adjacent to the amide had little effect on lipophilicity but led to a greater increase in oxidation potential. Lack of coplanarity and conjugation of the amide group and aromatic ring was also apparent with the analogues that had fluorine in the 2 and 6 positions. Introduction of fluorine into the amide group of paracetamol increased the lipophilicity 4-fold and also increased the oxidation potential of paracetamol. ED50 values for analgesic activity in the phenylquinone-induced abdominal constriction test on male Swiss White mice showed that ring substitution by fluorine reduced activity, especially at the 2,6-positions. Introduction of fluorine into the amide group enhanced activity significantly. Correlation of the analgesic activity with the physicochemical properties indicated that conjugation (and planarity) of the amide group with the aromatic ring is essential for activity and that ease of oxidation may also be an important factor.
- Barnard,Storr,O'Neill,Park
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p. 736 - 744
(2007/10/02)
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- NUCLEOPHILIC DISPLACEMENT IN POLYHALOGENAROMATIC COMPOUNDS. PART 12. ADDITIVITY OF FUORINE SUBSTITUENT EFFECTS IN METHOXYDEFLUORINATION
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The rates of methoxydefluorination of all twelve polyfluorobenzenes in dimethyl sulphoxide-methanol mixtures (DMSO-MeOH; 9:1 v/v; 298.2 K) have been measured.Three substituent rate factors (Fo, 60; fm, 180; fp, 0.75) are sufficient to reproduce the effect of the fluorine substituent in this reaction upon each member of the series.The solvent effect, comparing these results with an earlier and more limited study in methanol is predominantly a simple acceleration.The effects of substituents upon the rate of methoxydefluorination of fuorobenzene itself are slightly greater(ρ-, 6.9) than in the corresponding reaction of pentafluorobenzene derivatives (ρ-, 5.8) but the change in sensitivity is much less than that found with nitrobenzene derivatives.
- Bolton, R.,Sandall, J. P. B.
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p. 459 - 468
(2007/10/02)
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