Behaviour of 5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one and 5,6-dihydrothieno[3,2-h]cinnolin-3(2H)-one towards hydrazine. Synthesis of thienocinnolinones and of 4-aminothienocinnolinones

The isomeric compounds 5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one ( 7a ) and 5,6-dihydrothieno-[3,2-h]cinnolin-3(2H)-one ( 7b ) rapidly tautomerise to the corresponding 1,4-dihydrothienocinnolinones 8a,b when kept in refluxing hydrazine hydrate. With longer reaction times the initially formed 8a,b dehydrogenate to the thienocinnolinones 9a,b which eventually are aminated to 4-aminothienocinnolinones 10a,b . This behaviour recalls that reported for the related 5,6-dihydrobenzocinnolin-3(2H)-one ( 1 ) which under the same conditions undergoes dehydrogenation to benzo[h]cinnolin-3(2H)-one ( 2 ) followed by 4-amination to 3 , but differs for the stability of the intermediates, for the mechanism of the final amination, and for the higher reaction rate. All these differences can be rationalised in terms of the heats of formation of the intermediates and products of the two series of transformations.     

DNA damage induced by 4,6,8,9-tetramethyl-2H-furo[2,3-h]quinolin-2-one, a new furocoumarin analog: photochemical mechanisms

Some photochemical and photobiological properties of 4,6,8,9-tetramethyl-2H-furo[2,3-h]quinolin-2-one (HFQ) were studied in comparison with its isomer 1,4,6,8-tetramethyl-2H-furo[2,3-h]quinolin-2-one (FQ) and 8-methoxypsoralen (8-MOP). The HFQ photobinds to DNA forming furan-side monoadducts (MAHFQ) that have molecular structure very similar to those of FQ (MAFQ). Unlike MA8-MOP and MAFQ, MAHFQ no longer photoreact. The HFQ, like FQ, produces moderate amounts of singlet oxygen but no superoxide anions. The HFQ and FQ induce numbers of DNA-protein cross-links (DPC), much more plentiful than those of 8-MOP (about two and seven times, respectively) but no interstrand cross-links. The mechanism of DPC formation was studied in vivo in mammalian cells by alkaline elution and in vitro using a new test mixing histones and DNA from calf thymus. The latter is a very useful technique for the double irradiation protocol. The DNA (or histones) are separately exposed to a first UVA dose in the presence of the sensitizer; then, after its unbound molecules have been removed, histones (or DNA) are added to assemble the chromatin-like complex that is irradiated again. According to in vitro and in vivo methods, DPC appear to be formed by FQ and 8-MOP by a biphotonic process that starts with monoadduct induction in DNA, followed by their conversion into DPC. In the resulting lesions, the sensitizer molecule forms a covalent bridge between the two macromolecules (DPC at length greater than zero). Instead, HFQ induces DPC by a monophotonic process; thus, HFQ is probably not a physical part of the bridge between DNA and proteins, which may be linked together directly, like DPC at zero length induced by UVC.     

DNA damage induced by 4,6,8,9-tetramethyl-2H-furo[2,3-h]quinolin-2-one, a new furocoumarin analog: biological consequences

4,6,8,9-Tetramethyl-2H-furo[2,3-h]quinolin-2-one (HFQ) and its isomer FQ (1,4,6,8-tetramethyl-2H-furo[2,3-h]quinolin-2-one) showed very strong antiproliferative activity in mammalian cells, about two times greater than 8-methoxypsoralen (8-MOP). Both compounds induced DNA-protein cross-links (DPC) but not interstrand cross-links. The FQ generated DPC in a biphotonic process, yielding a new kind of diadduct, whereas HFQ induced DPC by a monophotonic one, probably without its physical participation in the covalent bridge. These lesions gave different toxic responses. Sensitization of FQ led to extensive DNA fragmentation and to a number of chromosomal aberrations. Conversely, HFQ seemed to be completely inactive and 8-MOP gave intermediate results. A strict relationship between DPC formation and induction of chromosomal aberrations was observed. The HFQ did not induce light skin erythemas, whereas FQ was more phototoxic than 8-MOP, thus suggesting that FQ lesions, DPC in particular, may be implicated in skin phototoxicity. Ehrlich ascites cells, a transplantable mouse tumor, inactivated by furoquinolinone sensitization and injected into healthy mice, protected them from a successive challenge by viable tumor cells. This response appeared to be based on an immune mechanism. Comparable amounts of base substitution revertants were scored when testing furoquinolinones and 8-MOP in bacteria but no DPC were detected. This suggests that classic mutagenesis tests on bacteria are insufficient to give adequate information on furocoumarin genotoxicity. Given its features, HFQ can be regarded as an interesting new agent for psoralen plus UVA photochemotherapy and photopheresis.     

Green synthesis of naphtho[2,3-f]quinolin-13-one and naphtho[2,3-a]acridin-1(2H)-one derivatives catalyzed by heteropoly acid supported montmorillonite K-10 clay

Herein, synthesis of a series of naphtho[2,3-f]quinolin-13-one and naphtho[2,3-a]acridin-1(2H)-one derivatives directly by one-pot multi-component reaction of 1,3-dicarbonyl compounds (1,3-indanedione/1,3-cyclohexanedione), 2-aminoantharacene/2-naphthylamine and various substituted aldehydes under solvent-free conditions using heteropoly-11-molybdo-1-vanadophosphoric acid supported on montmorillonite K-10 clay catalyst (10% PVMoK-10) is reported. The successful formation of naphtho[2,3-f]quinolin-13-one and naphtho[2,3-a]acridin-1(2H)-one derivatives was confirmed by various spectroscopic techniques. This study offers a green approach for the synthesis of novel quinolinone derivatives.     

Polyazasteroids II.. 1,2,4-Triazolol[3′,4′:2,3]pyrimido[4,5-c]quinolin- 11(12H)ones,imidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3] pyrimido[4,5-c]quinolin-11(12H)ones

Starting with 2-substituted quinoline-3,4-dicarboxylic acids, a series of substituted 1,2,3,4-tetrahydropyrimido[4,5-c]quinolinone-3-thiones were obtained. The latter compounds were converted to the three novel polyazasteroid series: 1,2,4-Triazolo[3′,4′:2,3]pyrimido[4,5-c]-quinolin-11(12H)ones, imidazo[2′,1′:2,3]pyrimido[4,5c]quinolin-11(12H)ones and 2,3-dihydroimidazo[2′,1′:2,3]pyrimido[4,5-c]quinolin-11(12H)ones. The intermediate 3-hydrazino-1,2-dihydropyrimido[4,5-c]quinolinones and nitrous acid gave the 3-azido derivatives rather than the tetrazolo compounds.     

Synthesis of imidazo[4,5-c]quinolin-4(5H)-one via radical cyclization

The tributyltin radical-induced cyclization of N-(2-bromophenyl)-Nbutyl-1H-1-methylimidazole-4-carbox-amide 3 gave 5-butyl-3-methyl-3H-imidazo[4,5-c]quinolin-4(5H)-one 5 via [1,2]-acyl rearrangement.     

Synthesis of 2H-benzo[2,3-g]pyridazino-[4,5-d,e]quinolin-3-one derivatives

Summary Condensation-cyclization of hydrazine with 4-methoxycarbonylbenzo[g]quinolinequinone or its corresponding carboxylic acid afforded 7-hydrazino-2H-benzo[2,3-g]pyridazino[4,5-d,e]-quinolin-3-one. Starting with the 9-hydroxy derivative, a similar double condensation of the nucleophile was observed, whereas its 6-hydroxylated regioisomer gave 2H-benzo[2,3-g]pyridazino-[4,5-d,e]quinolin-3,7-dione.

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Synthese von 2H-Benzo[2,3-g]pyridazino[4,5-d,e]chinolin-3-on-Derivaten

Zusammenfassung Die Kondensation/Zyklisierung von Hydrazin mit 4-Methoxycarbonylbenzo-[g]chinolinchinon bzw. mit der entsprechenden Carbonsäure ergab 7-Hydrazino-2H-benzo[2,3-g]-pyridazino[4,5-d,e]chinolin-3-on. Ausgehend vom 9-Hydroxy-Derivat, wurde in analoger Weise doppelte Kondensation des Nucleophils beobachtet, wohingegen das 6-Hydroxy-Regioisomer zu 2H-Benzo[2,3-g]pyridazino[4,5-d,e]chinolin-3,7-dion reagierte.

     

Synthesis of 2,10-diphenyl-2H-pyridazino[4,5-b]quinolin-1-one and 2,3-dihydro-9-phenyl-2-phenylamino-1H-pyrrolo[3,4-b]quinolin-1-one derivatives as peripheral-type benzodiazepine receptor ligands

The reaction of 2-chloromethyl-3-ethoxycarbonyl-4-phenylquinoline with phenylhydrazine, afforded 2,3-dihydro-9-phenyl-2-phenylamino-1H-pyrrolo[3,4-b]quinolin-1-one derivatives 2 along with a major amount of 3-ethoxycarbonyl-4-phenylquinoline-2-carboxaldehyde phenylhydrazone 4a . The geometric isomers of phenylhydrazone 4a , displaying solvent-dependent E-Z isomerism, were isolated, characterized by ¹H-nmr and mass spectra, and the Z-form easily cyclized to pyridazino[4,5-b]quinoline derivative 5a . Analogously, compounds 2b, 2c, 4b , 4c, 5b and 5c were obtained. The title compounds were tested as potential ligands for central and peripheral-type of benzodiazepine receptors, and the results are reported.     

Electron impact mass spectra of novel tetrahydroimidazo [4, 5, l-jk] [1, 4]benzodiazepin-2(1H)-one derivatives

Mass spectral fragmentations of nine benzodiazepin derivatives were examined by exact mass measurement and by metastable ion analysis. Under electron impact conditions, all compounds give rise to a molecular ion and ions of m/z 160, 159, 147, 131, 104, 77, 56, 41, and 39. Key fragmentation pathways are discussed for these ions.     

Facile Regioselective Synthesis of 2-Methyl Furo [3,2-c][1] benzopyran-4-one 2-Methyl Furo[2,3-c] [1]benzopyran-4-one

The title compounds (7 &8) were obtained in excellent yields from 4-[2′-chloroprop-2′-enyloxy] [1] benzopyran-2-one (5) and 3-[2′-chloroprop-2-enyloxy][1]benzopyran-2-one (6) via [3,3] sigmatropic rearrangement and cyclisation of the intermediate chloroallylic enols with conc. H₂SO₄. The reaction was also studied in N,N-dimethyl aniline.     

Synthesis of functionalized 2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones and their recyclization to 2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-ones

By the reaction of 6-aryl(alkyl)amino-5-cyano-2,3-dihydro-1,3-thiazin-4(10)-ones with α-halogenoketones in the presence of triethylamine, 2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones have been synthesized and their acid-catalyzed recyclization to 2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-ones has been found and studied. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:104–111, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20181     

Synthesis and microbial screening of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives

The present investigation describe the synthesis of 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Quinolin-8-ol was transformed by five step synthetic procedures into 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one. Subsequently, 8-Benzyloxy-5-(2-bromo-acetyl)-1H-quinolin-2-one condensed with 1,3-Diphenyl-1H-pyrazole-4-carbothioic acid amide in the presence of acetonitrile to afford 8-(benzyloxy)-5-(2-[1,3-diphenyl-1H-pyrazol-4-yl]thiazol-4-yl)quinolin-2(1H)-one derivatives. Synthesized compounds were screened for their antimicrobial activity against gram-positive and gram-negative bacteria. Most of the synthesized compounds are found to be active against tested bacterial strains and fungal strain.