الفهرس 
1.IntroductionOnly 14 pages are availabe for public view
 |  | from | 142 |  |  |
| | | from | 142 | | |
Abstract
Quinoline derivatives represent the major class of heterocycles, and anumber of preparations have been know since the late 1800s. The quinolone ring system occurs in various natural products, especially in alkaloids. The quinolone skeleton is often used for the design of many synthetic compounds with diverse pharmacological properties .
EthylEthylEthylEthylEthyl1-(2-ethoxyethoxyethoxyethoxyethoxyethoxy-2-oxoethyl)oxoethyl)oxoethyl)oxoethyl) oxoethyl)oxoethyl)oxoethyl)oxoethyl)-6-methymethy methymethyl -4-oxooxooxo- 1,41,4 dihydrodihydrodihydrodihydrodihydrodihydro -quinolinequinolinequinolinequinolinequinolinequinolinequinolinequinolinequinoline-3-carboxylate (carboxylate ( carboxylate (carboxylate (carboxylate (carboxylate (carboxylate ( carboxylate ( carboxylate (2) was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by was obtained by N-alkylation of alkylation of alkylation of alkylation of alkylation of alkylation of alkylation of alkylation of alkylation of alkylation of alkylation of 1 with ethyl with ethyl with ethyl with ethyl with ethyl with ethyl with ethyl with ethyl with ethyl with ethyl bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring bromoacetate in the presence of potassium carbonate stirring dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of dimethylformamide at room temperature. Hydrazinolysis of 2 at reflux at reflux at reflux at reflux at reflux at reflux afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate afforded the key intermediate 1-(2-hydrazinylhydrazinylhydrazinylhydrazinyl hydrazinylhydrazinylhydrazinyl-2-oxoethyl)oxoethyl)oxoethyl)oxoethyl)oxoethyl)oxoethyl)oxoethyl)oxoethyl)oxoethyl)-6-methylmethyl methylmethylmethyl-4-oxooxooxo-1,41,4 -dihydroquinolinedihydroquinolinedihydroquinolinedihydroquinolinedihydroquinolinedihydroquinoline dihydroquinolinedihydroquinolinedihydroquinolinedihydroquinolinedihydroquinolinedihydroquinolinedihydroquinolinedihydroquinolinedihydroquinoline-3-carbohydrazide carbohydrazide carbohydrazide carbohydrazide carbohydrazide carbohydrazide carbohydrazide carbohydrazide carbohydrazide carbohydrazide (3). Subsequently, . Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently,. Subsequently, 3 was was was treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, treated with carbon disulphide in the presence of potassium hydroxide, 3-(5-mercaptomercapto mercaptomercapto-1,3,41,3,4 1,3,4-oxadiazoloxadiazoloxadiazol oxadiazoloxadiazol oxadiazoloxadiazol-2-yl)yl)yl)-1-(( 5-mercaptomercapto mercapto-1,3,41,3,4 -oxadiazoloxadiazoloxadiazoloxadiazoloxadiazoloxadiazol oxadiazoloxadiazol-2-yl)methyl)yl)methyl)yl)methyl)yl)methyl)yl)methyl) yl)methyl)yl)methyl)yl)methyl)yl)methyl)-6-methylquinolinmethylquinolin methylquinolinmethylquinolinmethylquinolinmethylquinolinmethylquinolinmethylquinolinmethylquinolinmethylquinolinmethylquinolinmethylquinolinmethylquinolin-4(1H)-one one one (4) was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment was obtained. The treatment of of 4 with ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions l with ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions lwith ethyl chloroacetate under alkaline conditions leads to the eads to the eads to the eads to the eads to the eads to the eads to the eads to the eads to the eads to the eads to the corresponding ethyl corresponding ethyl corresponding ethylcorresponding ethylcorresponding ethylcorresponding ethylcorresponding ethylcorresponding ethylcorresponding ethylcorresponding ethylcorresponding ethylcorresponding ethylcorresponding ethylcorresponding ethyl corresponding ethylcorresponding ethylcorresponding ethyl2-(( 5- (( 3- (5-(( 2- ethoxyethoxyethoxyethoxyethoxyethoxy-2-oxoethyl)thoxoethyl)thoxoethyl)thoxoethyl)thoxoethyl)thoxoethyl)thoxoethyl)thoxoethyl)thoxoethyl)th oxoethyl)thio)io)io)-1,3,41,3,4 1,3,4oxadiazoloxadiazoloxadiazoloxadiazoloxadiazoloxadiazol oxadiazoloxadiazol-2-yl)yl)yl)-6-methylmethyl methylmethylmethyl-4-oxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolin-1(4H)-yl)methyl)yl)methyl)yl)methyl) yl)methyl) yl)methyl)yl)methyl)yl)methyl)yl)methyl)-1,3,41,3,4 1,3,4- oxadiazoloxadiazoloxadiazol oxadiazoloxadiazol oxadiazoloxadiazol-2-yl)yl)yl) thio)thio)thio)thio)thio) acetate acetate acetate acetate (5), on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation , on further condensation with hydrazin with hydrazin with hydrazin with hydrazin with hydrazin with hydrazin with hydrazin with hydrazin with hydrazin with hydrazin with hydrazin hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford hydrate to afford 2-(( 5-(( 3-(5-(( 2-hy drazinyldrazinyl drazinyldrazinyldrazinyl-2-oxoethyl)thio)oxoethyl)thio)oxoethyl)thio)oxoethyl)thio)oxoethyl)thio)oxoethyl)thio)oxoethyl)thio)oxoethyl)thio)oxoethyl)thio) oxoethyl)thio)oxoethyl)thio)oxoethyl)thio)oxoethyl)thio)-1,3,41,3,4 1,3,4oxadiazoloxadiazoloxadiazoloxadiazoloxadiazoloxadiazol oxadiazoloxadiazol-2-yl)yl)yl)-6-methylmethyl methylmethylmethyl-4-oxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolinoxoquinolin-1(4H)-yl)methyl)yl)methyl)yl)methyl) yl)methyl) yl)methyl)yl)methyl)yl)methyl)yl)methyl)-1,3,41,3,4 1,3,4 oxadiazoloxadiazoloxadiazol oxadiazoloxadiazol oxadiazoloxadiazol-2-yl)thio)yl)thio)yl)thio) yl)thio)yl)thio)yl)thio)yl)thio) acetohydrazideacetohydrazide acetohydrazideacetohydrazideacetohydrazideacetohydrazideacetohydrazide acetohydrazideacetohydrazideacetohydrazide (6) as shown in scheme 1.
English summary
II
Scheme (1)
The condensation of the dihydrazide 3 with 4-methoxybenzaldehyde, 2-
hydroxybenzaldehyde, or 2-chloro-6-fluorobenzaldehyde afforded N’-(4-
methoxybenzylidene)-1-(2-(2-(4-methoxybenzylidene)hydrazinyl)-2-
oxoethyl)-6-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazide (7), N’-
(2-hydroxybenzylidene)-1-(2-(-2-(2-hydroxybenzylidene)hydrazinyl)-2-
oxoethyl)-6-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazide (8),
and N’- (2- chloro -6- fluorobenzylidene)-1-(2-(2-(2-chloro-6-
fluorobenzylidene)hydrazinyl)-2-oxoethyl)-6-methyl-4-oxo-1,4-dihydroquinoline-
3-carbohydrazide (9), respectively. While the reaction of 3 with
ethoxymethylene malononitrile, ethyl ethoxymethylene cyanoacetate or
diethyl ethoxymethylenemalonate in acetic acid under reflux conditions
whether for 8 h or 10 h, the product obtained was identified as the
malononitrile derivative 11, cyanoacetate derivative 12 or malonate
English summary
III
derivative 13. Scheme (2) .
Scheme (2)
The reaction of hydrazide 3 with phenyl isothiocyanate in ethanol
gave the corresponding 2-(6-methyl-4-oxo-1-(2-oxo-2- (2- (phenylcarbamothioyl)
hydrazinyl)ethyl)-1,4 dihydroquinoline-3-carbonyl)-Nphenylhydrazinecarbothioamide
(14) in 89% yield. Based on the reaction
medium the thiadiazole, oxadiazole or triazole derivatives can be formed
during the cyclization reaction of the dithiosemicarbazide derivative 14.
Thus, stirring at 0 °C of 14 in the presence of sulfuric acid provided 6-
methyl-3-(5-(phenylamino)-1,3,4-thiadiazol-2-yl)-1-((5-(phenylamino)-
1,3,4-thiadiazol-2-yl)methyl)quinolin-4(1H)-one (15) in 71% yield. And
cyclization of 14 in the presence of HgO under reflux conditions gave 6-
methyl-3-(5-(phenylamino)-1,3,4-oxadiazol-2-yl)-1-((5-(phenylamino)-
1,3,4-oxadiazol-2-yl)methyl)quinolin-4(1H)-one (16) in 73% yield. While
the cyclization in the presence of NaOH under reflux conditions afforded
3-(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)-1-((5-mercapto-4-phenyl-
4H-1,2,4-triazol-3-yl)methyl)-6-methylquinolin-4(1H)-one (17) in 69%
yield. Subsequantly, 17 was reacted with ethyl chloroacetate leads to the
corresponding ethyl 2-((5-((3-(5-((2-ethoxy-2-oxoethyl)thio)-4-phenylEnglish
summary
IV
4H-1,2,4-triazol-3-yl)-6-methyl-4-oxoquinolin-1(4H)-yl)methyl)-4-
phenyl-4H-1,2,4-triazol-3-yl)thio)acetate (18).
Scheme(3)
The construction of the target compounds began by the
condensation of the acetohydrazide 19 with appropriate aldehyde
provided the corresponding arylidine carbohydrazide derivatives 20, 21,
and 22 as previously reported [16]. Followed by, N-alkylation with ethyl
iodide or ethyl chloroacetate in the presence of potassium carbonate
yielding the desired N-substituted quinolone Schiff base derivatives 23-27
(scheme 4).
English summary
V
Scheme (4)
With measuring the biological activity of the compounds resulting
that The synthesized intermediate (4)¡ (5)¡ (6) could effectively inhibit
the growth of many tested bacterial strains. Except compounds (3)¡ (7) ¡
(11) and 13 showed moderate activities against many tested bacterial
strains. Compound 15 with thiadiazole moieties at the 1-and 3-
poisitions of quinoline backbone gave broad bioactive spectrum against
all Gram- Positive and Gram-Negative strains. While compounds 17
and 18 with triazole moieties at 1-and 3-poisitions showed specific
activity against specific tested bacterial strains. The synthesized arylidine
carbohydrazide derivatives (20) ¡ (21) ¡ (25) ¡ (26) ¡ (27) showed no
activity against most of the tested Gram-Positive and Gram-Negative
strains. Expect against some bacterial strains was sensitive to the
compounds (20) ¡ (25) ¡ (26) compounds.
Also it will be prove the chemical composition of the compounds
produced by various spectroscopic and analytical devices such as infrared
and magnetic resonance and mass spectrometry in addition to elemental
analysis of carbon, hydrogen and nitrogen.