Jalal A. Zahra

HETEROCYCLES (H)-FUSED TO 4-OXOQUINOLINE-3-CARBOXYLIC ACID. PART IX. 1 SYNTHESIS OF 2,6-DIOXOTETRAHYDRO-1H- PYRROLO(3,2-H)QUINOLINE-7-CARBOXYLIC ACID

Interaction of deprotonated malonic esters with 7-chloro-8-nitro-4- oxoquinoline-3-carboxylate (1) gave the respective 7-(bis(alkoxycarbonyl)- methyl) derivatives (2, 3) which were converted into the corresponding 7-(carboxymethyl)-8-nitro-4-oxoquinoline-3-carboxylic acid (4). Reductive lactamization of the latter furnished the target tetrahydro-2,6-dioxo-1H-pyrrolo- (3,2-h)quinoline-7-carboxylic acid (5). Both compounds 4 and 5 exhibited broad spectrum of high antibacterial activity against representatives of Gram-negative and Gram-positive bacteria classes, but were less potent than the reference ciprofloxacin.

Reaction of Nitrilimines with 2-Substituted Aza-heterocycles. Synthesis of Pyrrolo[1,2-a]pyridine and Pyrimido[2,1-d]1,2,3,5- tetrazine

The reaction of nitrilimine 6a with ethyl pyridine-2-acetate (7) gave the corresponding pyrrolo[1,2-a]pyridine 8, while the reaction of 6b containing an ester moiety afforded the acyclic adduct 9. The reaction of 6a with 2-aminopyrimidine (10) gave the novel unexpected pyrimido[2,1-d]1,2,3,5-tetrazine 11. Acyclic adducts 16 and 17 were obtained from the reaction of 6b with 2-cyanomethylbenzimidazole (14) and 2-aminobenzimidazole (15), respectively.

Heterocycles [h]Fused onto 4-Oxoquinoline-3-Carboxylic Acid, Part IV. Convenient Synthesis of Substituted Hexahydro [1,4]Thiazepino[2,3-h]quinoline-9-carboxylic Acid and Its Tetrahydroquino[7,8-b]benzothiazepine Homolog

Substituted [1,4]thiazepino[2,3-h]quinolinecarboxylic acid 3 is prepared by PPA-catalyzed thermal lactamization of the respective 8-amino-7-[(2-carboxyethyl)thio]-1,4-dihydroquinoline-3-carboxylic acid 9. The latter synthon is obtained by reduction of the 8-nitro-1,4-dihydroquinoline precursor 8 which, in turn, is made accessible via interaction of 3-mercaptopropionic acid with 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-1,4-dihydroquinoline-3-carboxylic acid 7 in the presence of triethylamine. A benzo-homolog of 3, namely tetrahydroquino[7,8-b]benzothiazepine-3-carboxylic acid 6, is analogously prepared via the reaction of 2-mercaptobenzoic acid with 7, followed by reduction of the resulting 7-[(2-carboxyphenyl)thio]-8-nitro product 10 into the corresponding 8-amino derivative 11, and subsequent lactamization. The structures assigned to 3, 6 and 8-11 are based on microanalytical and spectral (IR, MS, NMR) data.

Investigations on the structure of 4-methyldihydro-1,3,4-benzotriazepin-5-ones. Tautomer reassignment

The tautomerism of 4-methyldihydro-1,3,4-benzotriazepin-5-ones (2,3) is re-investigated by means of X-ray diffraction and quantum chemical calculations. The data revealed that the model compound (2a) exists in the amidrazone 1,4-dihydro tautomeric form (A), but not in the alternate 3,4-dihydro tautomer (B) as was previously reported.

Heterocycles [h]-Fused onto 4-Oxoquinoline-3-carboxylic Acid, V [1]. Synthesis and Antibacterial Activity of Some New 2,3-Disubstituted 7-Oxo-7,10-dihydropyrido[2,3-f]quinoxaline-8-carboxylic Acids and Esters

Cyclocondensation reaction of ethyl 7,8-diamino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline- 3-carboxylate (2) or the -3-carboxylic acid 3 with sym-1,2- diketones produced the corresponding ethyl 2,3-disubstituted pyrido[2,3- f ]quinoxaline-8-carboxylates (4a - h) or the -8-carboxylic acids 5a - h, respectively. The structures for these new heterocycles are supported by analytical and spectral (IR, MS, NMR) data. Compounds 5a - c, g, h exhibit moderate activity against an assortment of bacterial species.

Heterocycles [h]-fused to 4-oxoquinoline-3-carboxylic acid. Part XI: Synthesis and antibacterial activity of 4-fluoro-6-oxoimidazo[4,5-h]quinoline-7-carboxylic acids

Abstract A series of 2-hetaryl-4-fluoro-9-cyclopropyl-6-oxo-1H-imidazo[4,5-h]quinoline-7-carboxylic esters (3a–f) and their corresponding acids 4a–f have been prepared via microwave-assisted cyclocondensation reaction with some hetarene carboxaldehydes. The structures for these new esters and acids are based on spectral (IR, MS, and NMR) data. The in vitro antimicrobial assay of 4a–f hetaryl derivatives, their aryl analogues 1d–g, and the imidazo-unsubstituted acid 1a showed that all of these tricyclic heterocycles possess a good level of antibacterial activity. Among them, compound 1a exhibited the highest effect against both, Gram-positive (minimum inhibitory concentrations [MICs] 0.15–3.0 μg mL–1) and Gram-negative bacteria (MICs 0.7–3.0 μg mL–1). An excellent activity was recorded also for the halo-phenyl derivatives 1f,g and for the furan derivatives 4e,f, especially toward Gram-positive strains and Bacillus subtilis and Haemophilus influenzae, respectively.

A facile synthesis of novel pyridone-annelated spirooxindolepyrrolidines via 1,3-dipolar cycloaddition

A series of novel pyridine-annelated spirooxindole-3,2′-pyrrolidines was prepared via 1,3-cycloaddition reaction involving N-methylmaleimide as 1,3-dipolarophile and the appropriate azomethine ylide. The latter 1,3-dipolar species were generated in situ via decarboxylative condensation reaction of the particular α-amino acid with pyridine-annelated isatin in aqueous methanol under reflux. The structures of these new spirooxindole cycloadducts are based on microanalytical, spectral (IR, HRMS, and NMR), and X-ray crystal data.Graphical Abstract

Design synthesis and antibacterial activity studies of new thiadiazoloquinolone compounds

Abstract New 9-(alkyl/aryl)-4-fluoro-6-oxo[1,2,5]thiadiazolo[3,4-h]quinoline-5-carboxylic acids and their esters were designed and synthesized. A detailed discussion of the reactions utilized in the preparation of the intermediate and target compounds is reported. All the newly synthesized compounds were fully characterized using all the physico-chemical means needed. All the intermediates and the final esters and acids were tested against bacterial and fungal strains. The acids 25a and 25c proved to be very active against Gram positive and Gram negative bacteria with MIC 0.15–3 µg/mL. The structure–activity relationship of antibacterial thiadiazoloquinolones shows that compounds 25a and 25c are twice less potent than the corresponding cyclopropyl derivative 16. Therefore, the cyclopropyl moiety on N-9 seems to be the most suitable substituent.

Synthesis of Some Ethyl 3-(Aryldiazenyl)-7-oxo-dihydropyrido[ 2,3-f]quinoxaline-8-carboxylates

Ethyl 7,8-diamino-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (6) and its free acid 7 are prepared by chemical reduction of the respective 7-azido-8-nitroquinoline 5. Consecutive nucleophilic addition and cyclocondensation reactions of 6 with α-acetyl-N-arylhydrazonoyl chlorides 8a - c in ethanol and triethylamine are site-selective and yield the corresponding 3-(aryldiazinyl)- 2-methylpyrido[2,3- f ]quinoxalines 10a - c. Analytical and spectral (IR, MS, NMR) data of 6, 7, and 10a - c are in conformity with the assigned structures.

Ring size influence on the cyclocondensation mode of GABA: Nitrile imine adducts

Abstract γ -Aminobutyric acid (GABA) adds onto nitrile imine 1,3-dipolar species (generated in situ from their N-arylhydrazonoyl chloride precursors 1a-c ) to deliver the corresponding acyclic amidrazone adducts 10a-c. In the presence of 1,1’-carbonyldiimidazole, the latter adducts undergo cyclocondensation involving the activated carboxyl and the amidrazone-CH2NH groups to afford the respective N-[1-(arylhydrazono)-2-oxopropan-1-yl] pyrrolidin-2-ones (11a-c). The constitution of 10 and 11 is evidenced from analytical and spectral (IR , MS and NMR) data.