E. V. Nosova

Fluorine-containing heterocycles: XII. fluorine-containing quinazolin-4-ones and azolo[a]quinazolinone derivatives

Methods for the synthesis of fluorine-containing derivatives of 2-imino-1,3-diphenylquinazolin-4-one, imidazo[1,2-a]quinazolin-5-one, pyrazolo[1,5-a]quinazolin-5-one, and [1,2,4]triazolo[1,5-a]quinazolin-5-one were developed on the basis of the reaction of tetrafluorobenzoyl chloride with N,N′-diphenylguanidine and aminoazoles.

Fluorine-Containing Heterocycles: XIX.* Synthesis of Fluorine-Containing Quinazolin-4-ones from 3,1-Benzoxazin-4-ones

Reactions of fluorine-containing 3,1-benzoxazin-4-ones with ammonium acetate, hydrazine, and heteroaromatic amines gave new 3H-, 3-amino-, and 3-hetarylquinazolin-4-ones, respectively. Differences in the conditions of formation of benzoxazinones from anthranilic acids with different fluorination patterns and in the reactions of fluorinated 3,1-benzoxazinones with nitrogen-centered nucleophiles were revealed.

Fluorine-containing heterocycles: XVII. (Tetrafluorobrnzoyl)thioureas in the synthesis of fluorine-containing azaheterocycles

Proceeding from (tetrafluorobenzoyl)thioureas fluorine-containing derivatives were synthesized of 1-aryl-2-ethylthioquinazolin-4-one, [1,3]benzothiazin-4-one, and also of thiazolidine and 1H-1,2,4-triazole.

Fluorine-containing heterocycles: XVIII. Monofluoro derivatives of quinazolines and 1,3-benzothiazin-4-ones

Abstract5- and 7-Fluoro-substituted quinazolines and 1,3-benzothiazin-4-ones were synthesized starting from 2-amino-6-fluorobenzonitrile and mono- and difluoro-substituted benzoic acid derivatives. The reactivities of di- and tetrafluoro-substituted benzoyl chlorides and benzoyl isothiocyanates in cyclocondensations leading to fluorinated quinazolines and 1,3-benzothiazines were compared.

Synthesis of 5-and 7-fluoroquinazolin-4(1H)-ones

Abstract5-Fluoroquinazoline-2,4-diones and their 2-thio analogs were obtained from 6-fluoroanthranilic acid. Two convenient routes to 5-fluoroquinazolin-4-ones involved cyclocondensation of 6-fluoroanthranilamide with acid chlorides (anhydrides) or with aromatic (heterocyclic) aldehydes. A method for the synthesis of 7-fluoroquinazolin-4-one from 2,4-difluorobenzoic acid was proposed.

Synthesis and Antibacterial Activity of 1,3,4-Thia(oxa)diazino[6,5,4-i,j]quinoline Derivatives

Synthetic compounds of the fluoroquinolone group, representing derivatives of 4-oxo-1,4-dihydro-3-quinolinecarboxylic acid, are widely used as antibacterial drugs (pefloxacin, norfloxacin, ciprofloxacin, etc.) [1 – 3]. Besides the therapeutic breadth and high level of activity, an important advantage of fluoroquinolones in comparison to -lactams (penicillins, cephalosporins), aminoglycosides, and some other antibiotics is their high chemical stability. Experiments on the chimeric modification of fluoroquinolones have been conducted for more than a decade [3 – 5]. In recent years, considerable attention of researchers has been devoted to the condensed fluoroquinolones, the most widely known representatives of which are ofloxacin and marbofloxacin [6, 7]. We have developed new approaches to the synthesis of annelated fluoroquinolones [8, 9] based on the intramolecular cyclization of ethyl esters of 3-[R-carbonyl(thiocarbonyl)hydrazino]-2-tetra(penta)fluorobenzoylacrylic acid. Using this method, we obtained ethyl esters of 1,3,4-thia(oxa)diazino[6,5,4-i,j]quinoline-6-carboxylic acids and determined the conditions for hydrolysis of the ester groups and for replacement of the fluorine atoms in positions 8 and 10. This allowed us to synthesize a series of modified fluoroquinolones Ia – Ik and IIa – IIe. The synthesis of ethyl esters of 1,3,4-thia(oxa)diazino[6,5,4-i,j]quinoline-6-carboxylic acid was described in detail in [9, 10] and the synthesis of compounds Ia – Ik was reported in [11]. For this reason, below we describe only the synthesis of previously unreported 1,3,4-oxadiazino[6,5,4-i,j]quinolines (IIa – IIe). Since compounds Ia – Ik are representatives of a new heterocyclic system containing fluoroquinolone fragments and compounds IIa – IIe are the analogs of marbofloxacin, it was interesting to evaluate the antimicrobial activity of these substances. EXPERIMENTAL CHEMICAL PART

Metallocomplexes of fluoroquinolonecarboxylic acids

The survey reviews the data on the synthesis, structure and biological activity of fluoroquinolonecarboxylic acids metal chelates. The influence of metal and ligand nature as well as conditions of the synthesis on the polyhedron type is discussed. The data on interaction between fluoroquinolone metal complexes and DNA are explored.

Fluorine-containing heterocycles: XV. Reactions of polyfluorobenzoyl isothiocyanates with aminoazines and aminoazoles

Reactions of tetra-and pentafluorobenzoyl isothiocyanates with aminoazoles and aminoazines led to the formation of fluorinated 1,3-benzothiazin-4-ones which reacted with cyclic amines in different ways. Replacement of the N=C=S fragment was observed in some reactions of polyfluorobenzoyl isothiocyanates with nucleophiles.

Polyfluorobenzoyl chlorides and isothiocyanates in reactions with CH-reactive benzimidazoles

Reactions of 2-benzoylmethylbenzimidazole with tetra- and pentafluorobenzoyl chlorides afford fluorine-containing 6-benzoyl-7H-benzimidazo[3,2-a]quinolones. 2-Cyanomethyl- or 2-benzoylmethylbenzimidazole reacts with tetra(penta) fluorobenzoyl isothiocyanates to give fluorine containing 1,3-benzothiazinones, which differently behave in reactions with cycloalkylimines.

Fluorocontaining Heterocycles: IX. Derivatives of Imidazo[2,1-b][1,3]benzothiazine

The heating of derivatives of benzimidazole-2-thione and imidazolidine-2-thione with tetra(penta)fluorobenzoyl chlorides in toluene or pyridine gave rise to fluorocontaining derivatives of imidazo[2,1-b][1,3]benzothiazine. The latter were studied in reactions of nucleophilic substitution of fluorine for amino groups.