Band 24, Heft 4

Methyl 2-[(cyanophenoxy)methyl]-3-furoates obtained from methyl 2-(chloromethyl)-3-furoate and salicylonitriles undergo tandem cyclization in the presence of excess t -BuOK in N,N-dimethylformamide (DMF) solution at 65°C to give substituted benzofuro[3,2- b ]furo[2,3- d ]pyridin-4(5 H )-ones, derivatives of a novel heterocyclic system.

Derivatives of the new heterocyclic system, 6 H -chromeno[4,3 -e ]pyrazolo[5,1 -c ][1,2,4]triazin-6-one, were obtained by the reaction of pyrazole-3(5)-diazonium salts with 4-hydroxy-2 H -chromen-2-one. Similar reactions with 5-phenyl-3 H -furan-2-one followed by intramolecular heterocyclization furnished 6-(4-halophenyl)-7-alkyl-2-phenylfuro[2,3 -e ]pyrazolo[5,1 -c ][1,2,4]triazines.

A rapid one-pot reaction of epoxides with ethyl mercaptoacetate furnishing 1,4-oxathian-2-ones in the presence of a catalytic amount of eco-friendly triton B is reported. High regioselectivity is due to the nucleophilic attack on the less sterically hindered carbon atom of the aliphatic unsymmetrical epoxide.

The oxidation of 1,4-diacetylbenzene using several oxidizing agents gave 1,4-phenylene-bis-glyoxal in 61–85% yields. A convenient and efficient synthesis of bis-quinoxaline and bis-pyrido[2,3- b ]pyrazine derivatives involves the double condensation of 1,2-diamines with 1,4-phenylene-bis-glyoxal in ethanol under reflux conditions. The structures of the new products were defined by proton nuclear magnetic resonance ( 1 H NMR), carbon-13 nuclear magnetic resonance ( 13 C NMR), Fourier-transform infrared spectroscopy (FT-IR) and mass spectrometry (MS).

The reactions of [1,3]thiazolo[3,2- b ][1,2,4]triazol-7-ium salts with nucleophiles were investigated. Theoretical investigation of reactivity descriptors and structural parameters of [1,3]thiazolo[3,2- b ][1,2,4]triazol-7-ium cation was carried out, and the reactivity centers of the model salts were located. An efficient general method for the synthesis of novel poly-functional derivatives of symmetric triazoles from [1,3]thiazolo[3,2- b ][1,2,4]triazol-7-ium halides was developed. The structures of the synthesized compounds were confirmed using proton nuclear magnetic resonance ( 1 H NMR), carbon-13 nuclear magnetic resonance ( 13 C NMR), Fourier-transform infrared spectroscopy (FTIR) and single-crystal X-ray analysis.

2-(4-Bromophenyl)-1-(3-chloro-2-methylphenyl)- 4,5-diphenyl-1 H -imidazole ( 1 ) and 1-(3-chloro-2-methylphenyl)-2-(4-chlorophenyl)-4,5-diphenyl-1 H -imidazole ( 2 ) were synthesized by one-pot four-component reactions. These compounds crystallize in the monoclinic crystal system with the space group P 2 1 / n . The crystal structures were solved by direct methods and refined by a full matrix least squares procedure to a final R value of 0.0572 ( 1 ) and 0.0588 ( 2 ) for 2748 and 2278 observed reflections, respectively. Molecular docking studies were implemented to understand the inhibitory activity of related compounds against glucosamine 6-phosphate (GlcN-6-P) synthase, the target protein for the antimicrobial agents.

Indibulin is one of the most potent tubulin polymerization inhibitors with minimal peripheral neuropathy. The design and synthesis of new indibulin analogs were carried out in order to investigate their anti-cancer activity. The target compounds 4a–i were synthesized in multistep reactions starting with the related indole derivatives. Compound 4f shows the highest cytotoxic activity on HT-29 and Caco-2 cell lines with the respective half maximal inhibitory concentration (IC 50 ) values of 5.1 μ m and 7.3 μ m . In the case of the T47-D cell line, compound 4c exerts the best cytotoxic activity with an IC 50 value of 11.5 μ m . In the cell cycle analysis on HT-29 cells, compound 4f at 5.1 μ m showed an increase in the percentage of cells in the sub-G1 phase. Altogether, nine target compounds were synthesized and characterized by infrared spectroscopy (IR), proton nuclear magnetic resonance ( 1 H NMR), carbon-13 nuclear magnetic resonance ( 13 C NMR), mass spectrometry (MS) and elemental analysis. Some of the compounds show good cytotoxic activity against cancerous cell lines.

Dibenzothiazepine analogues containing lactam, amidine and imine moieties were prepared from 2-aminophenyl disulfides via one-pot S -arylation. The S -arylation involved cleavage of an S-S bond of disulfides and S N Ar reaction in aqueous ammonia solution of L-cysteine to afford diaryl sulfides. Dibenzothiazepine analogues having lactam and amidine moieties were obtained by cyclization of the corresponding diaryl sulfides under acidic conditions. One-pot S -arylation of 2-bromo-5-nitrobenzaldehyde gave dibenzothiazepine analogues with an imine moiety in one step through intramolecular cyclization. Compounds with antibacterial activities against Staphylococcus aureus and Escherichia coli were obtained.

Xanthone derivatives of acetic, propionic and 2-methylpropionic acids were synthesized and assayed for their anti-inflammatory, analgesic and ulcerogenic activities. Compound 8 causes a dose-dependent diminution of paw edema (up to 61%) in the carrageenan model and at the highest tested dose reduces mechanical hyperalgesia in the Randall-Selitto test more effectively than the reference compound (~75% and ~32%, respectively). It shows high in vitro metabolic stability (Cl int =12.5 μL/mg/min, t 1/2 =138.6 min) in the rat liver microsomes. None of the studied xanthone derivatives are ulcerogenic. The results of the present study suggest that compound 8 can be of interest in the future for the search for antinociceptive and antiedematous agents devoid of ulcerogenic effect.

Syntheses of 3-(4-arylthieno[2,3- d ]pyrimidin-2-yl)-2 H -chromen-2-ones 5 by the reaction of 2-iminocoumarin-3-carboxamides 1 with (2-aminothiophen-3-yl)(aryl)methanones 2 and by the alternative Suzuki coupling of 4-chlorothieno[2,3- d ]pyrimidin-2-yl-2 H -chromen-2-one 7 with arylboronic acids were developed. Compound 5d showed higher antimicrobial activity against Staphylococcus aureus than the reference drug streptomycin.