• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The invention relates to derivatives of quinoline-carboxylic acid (HRP), in particular the preparation of compounds of the general formula F COHH Ri where R, is C, -C-alksh1; R and R, - H, C, -C-alkyl, which have antibacterial activity and can be used in medicine. The goal is to develop an affordable way to obtain useful compounds. Synthesis of HRPs is carried out from 1,3-chloroacetone and, for example, ethyl-1-ethyl-6-fluoro-7-thiocarbamoyl-1,4-dihydro-4-oxo-3-quinolI-carboxylate in the presence of N, N- dimethylformamide when heated. The product is then treated with sodium azide, followed by reduction with hydrogen in the presence of palladium on carbon as a catalyst. Compared to the known 7- (3-amino-1-pyrrolidinyl) -1-ethyl-6-fluoro-1,4-dihydro-4-oKCo-1, 8-naphthyridine-3-carboxylic acid HRPs exhibit better antibacterial activity without toxicity. 1 tab. i O)
    公开号:SU1321376A3
    申请号:SU843732809
    申请日:1984-04-27
    公开日:1987-06-30
    发明作者:П.Кубертсон Таунли；М.Домагала Джон；Ф.Мич Тома；Б.Николс Джеффри
    申请人:Варнер-Ламберт Компани (Фирма)；
    IPC主号:
    专利说明:

     CM
    eleven
    The invention relates to organic chemistry, namely to a method for producing new quinoline carboxylic acid derivatives of the general formula
    F.
    (I)
    КзК2 МШ2-Й
    where RJ is C, -C-Alksh1; K, IR, - And, C, -C-alkyl, which exhibit antibacterial activity and can be used in medicine.
    The aim of the invention is to develop a process for the preparation of compounds of formula I which exhibit high antibacterial activity.
    Example 1. 7-C4- (Aminomethyl) -2-thiazolyl -1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid.
    A solution of 0.16 g (0.5 mmol) of 7-thiocarbamoyl-1,4-dihydro-4-oxo-3-quinoline-carboxylate-methyl 7-thiocarbamoyl-1,4-dihydro-4-oxo-3-fluorine and 0.32 g (2.5 mmol) 1,3-dichloro-acetone in 3 mp H, H-dimethylformamide is heated for 3.5 hours on a steam bath. Dissolving the cooled reaction mixture with ethyl acetate gives 0.12 g of product which is recrystallized from chloroform - ethyl acetate to obtain 0.08 g of ethyl acetate (Chloromethyl) -2-thiazolyl -1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid ester, m.p. 214-215 C (with decomposition).
    A mixture of 1.10 g (2.78 mmol) of ethyl (chloromethyl) -2-thiazolyl-1-ethyl-6-fluoro-1,4-DIHYDRO-4-OK-co-3-quinolinecarboxylic acid ethyl ester and 0, 50 g (7.6 mmol) of sodium azide in 50 ml of H, M-dimethylformamide is heated on the steam bath for 4 hours. After evaporation to an almost dry residue, 50 ml of water is added to give 1.01 g of product, which is crystallized from ethanol to obtain 0.91 g of ethyl 7-t4- (azidomethyl) -2 -2-thiazolyl -1-ethyl-6-fluorophen-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, t, b1. 192-194 ° C (with decomposition).
    A solution of 0.87 g (2.17 mmol) of ethyl ester (azidomethyl) -2- -thiazalyl -1-ethyl-6-fluoropi-1, 4-dihyd 0
    321376 2
    ro-4-oxo-3-quinolinecarboxylic acid in 125 mm of acetic acid is mixed with 0.10 g of 10% palladium on carbon as a catalyst and hydrogen is passed through a hydrogen gas for 5 h. After filtration, evaporation of the solvent and trituration with ether, 0.77 g of ethyl ethyl 7-4- (aminomethyl) -2-thiazolyl -1 -1-ethyl 6-fluoro-1,4-DIGIDRO-4-OXO-3 are obtained. - quinolinecarboxylic acid.
    A solution of 0.70 g (1.87 mmol) of (aminomethyl) -2- -thiazolyl-1-ethyl-6-otor-1, 4-dihyd-5 ro-4-oxo-3-quinolinecarboxylic acid ethyl ester in 15 ml 6 n. Hydrochloric acid is heated on a steam bath for 2.25 hours. After adding 15 ml of water, the mixture is cooled to 0 ° C and filtered. The collected solid is suspended in 8 ml of water, dissolved at pH 11 in 2 n sodium hydroxide and re-precipitated by the addition of 2 n. hydrochloric acid to pH 6. The product (0.37 g) is crystallized twice from M, N-dimethylformamide to give O, 19 g (57% of theoretical) (aminomethyl) -2-thiazolyl-1-ethyl-6- fluoro-1,4-dichloro-4-oxo-3-quinolinecarboxylic acid, mp, 224-226 ° C (with decomposition).
    Found,%: C 55; H 4.28 | N 11.79.
    20
    thirty
    35
    C, gH, N, FOjS
    40
    45
    Calculated,%: C 55.32, H 4.06, N 12.
    Example 2, 1-Ethyl-6-fluoro-1,4-dihydro-7-4-(methylamino) methyl 3-2-thiazolyl 3-oxo-3-quinolinecarboxylic acid.
    A solution of 0.61 g (1.54 mmol) of 7- (4-chloromethyl-2-thiazolyl) -1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3 ethyl ester -quinolinecarboxylic acid in 20 ml 6 n. The hydrochloric acid is refluxed for 2 hours and evaporated to dryness. The resulting solid is suspended in hot water, filtered and dried to give 0.48 g of the crude product — 7- (4-chloromethyl-2- -thiazolyl) -i-e-6-fluoro-1,4-dihydro -4-oxo-3-quinolinecarboxylic acid-, lots.
    A solution of 0.40 g of 7- (4-chloromethyl-2-55-thiazolyl) -ethyl-6-fluoro-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid in 100 ml of 40% aqueous methylamine stirred at room temperature-50
    35
    C, gH, N, FOjS
    40
    45
    Calculated,%: C 55.32, H 4.06, N 12.
    Example 2, 1-Ethyl-6-fluoro-1,4-dihydro-7-4-(methylamino) methyl 3-2-thiazolyl 3-oxo-3-quinolinecarboxylic acid.
    A solution of 0.61 g (1.54 mmol) of 7- (4-chloromethyl-2-thiazolyl) -1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3 ethyl ester -quinolinecarboxylic acid in 20 ml 6 n. The hydrochloric acid is refluxed for 2 hours and evaporated to dryness. The resulting solid is suspended in hot water, filtered and dried to give 0.48 g of the crude product — 7- (4-chloromethyl-2- -thiazolyl) -i-e-6-fluoro-1,4-dihydro -4-oxo-3-quinolinecarboxylic acid-, lots.
    A solution of 0.40 g of 7- (4-chloromethyl-2-55-thiazolyl) -ethyl-6-fluoro-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid in 100 ml of 40% aqueous methylamine stirred at room temperature-50
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining quinolinecarboxylic acid derivatives of the formula
    ABOUT
    . .. .sleep
    R
    tour overnight and evaporated to dryness. The resulting solid is crystallized from water to obtain 0.33 g of the desired compound, t, n. 216-217 C (with decomposition). Yield 85%.
    Calculated,%: C 55.94, H 4.53, N 11.51.
    C,., H, gN, 0.2 NdO
    Found,%: C 55.92, H 4.41, fO N 11.18.
    The proposed compound exhibits where R, -C, -C4-alkyl, antibacterial activity with non-, -H, C, -Cz-alkyl, by microtiter method, characterized in that the dilution ./5 is a compound of the general formula
    Using the method described above, the obtained minimum inhibitory concentration (MIC) values for the proposed compounds and the known compound 7- (3-amino-1-pyrrolidi-20 .NIL) -1-ethyl-6-fluoro-1,4-DIGIDRO- 4-OC-co-1,8-naphthyridine-3-carboxylic acid is reacted with 1,3-chloro-lota given in table. With acetone when heated in the medium. Thus, compounds of total methylformamide followed by formula I, obtained by treating the product obtained with an azide method 25, have a higher sodium and subsequent recovery anovleni- antibacterial activity comparable eat azide with hydrogen and nenii to known compounds without palladium on carbon as a catalytic manifestations toksichnosti.zatora.
    Invention Formula
    The method of obtaining quinolinecarboxylic acid derivatives of the formula
    ABOUT
    . .. .sleep
    R
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    同族专利:
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    US52227583A| true| 1983-08-12|1983-08-12|
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