Synthesis of imidazo[4,5-][1,3]thiazino[2,3-][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-]thiazolo[2,3-][1,2,4]triazines.

A series of imidazo[4,5-][1,3]thiazino[2,3-][1,2,4]triazines was synthesized via a cascade sequence of hydrolysis and skeletal rearrangement of imidazo[4,5-]thiazolo[2,3-][1,2,4]triazin-7(8)-ylidene)acetic acid esters in methanol upon treatment with excess KOH. Imidazo[4,5-]thiazolo[3,2-][1,2,4]triazin-6(7)-ylidene)acetic acid esters are also suitable substrates for the reaction. In this case hydrolysis and thiazole ring expansion were accompanied with the change of the thiazolotriazine junction type from thiazolo[3,2-][1,2,4]triazine to thiazino[2,3-][1,2,4]triazine.

Regioselective synthesis of 3,4-diaryl-5-unsubstituted isoxazoles, analogues of natural cytostatic combretastatin A4.

4,5-Diarylisoxazoles are potent antiproliferative tubulin-targeting agents. Their isomeric 3,4-diaryl-5-unsubstituted isoxazoles are hardly accessible. The synthesis of 3,4-diaryl-5-unsubstituted isoxazoles 13 was designed based on a condensation of arylbenzaldehydes, arylnitromethanes, and ethoxycarbonylmethylpyridinium bromide followed by a selective one-step transformation of intermediate 3,4-diaryl-5-ethoxycarbonyl-4,5-dihydroisoxazole 2-oxides 8.

Synthesis and anti-mitotic activity of 6,7-dihydro-4H-isothiazolo[4,5-b]pyridin-5-ones: In vivo and cell-based studies.

A series of 3,7-diaryl-6,7-dihydroisothiazolo [4,5-b]pyridin-5(4H)-ones 8 and 9 was synthesized by multicomponent condensation of 3-aryl-5-isothiazolecarboxylic acid esters 4a-f with aromatic (or thienyl) aldehydes 7 and Meldrum's acid in an acidic medium. The targeted compounds were evaluated for their antimitotic microtubule destabilizing activity using in vivo phenotypic sea urchin embryo model and in vitro human cancer cell-based assays. Selected dihydroisothiazolopyridinones altered sea urchin egg cleavage in 2-10 nM concentrations together with significant cytotoxicity against cancer cells including chemoresistant cell lines (IC in submicromolar - low nanomolar concentration range).

Synthesis, structure, and properties of supramolecular photoswitches based on ammonioalkyl derivatives of crown ether styryl dyes.

The synthesis of new styryl dyes derived from 4-pyridine and 4-quinoline and having an ammonioalkyl N-substituent and benzocrown ether moieties of different sizes and with different sets of heteroatoms was developed. Spontaneous "head-to-tail" dimerization of these dyes via the formation of numerous hydrogen bonds between the terminal NH3(+) groups and crown ether moieties was detected in MeCN solutions. The stability constants of the dimeric complexes having pseudocyclic structure were studied by (1)H NMR titration.

Synthesis, structure, and characterization of chromo(fluoro)ionophores with cation-triggered emission based on N-methylaza-crown-ether styryl dyes.

Novel 2-benzothiazole-, 4-pyridine-, and 2- and 4-quinoline-based styryl dyes containing an N-methylbenzoaza-15(18)-crown-5(6)-ether moiety were synthesized. A detailed electronic spectroscopy study revealed high performance of these compounds as optical molecular sensors for alkali and alkaline-earth metal cations. They were shown to considerably surpass analogous chromoionophores based on N-phenylaza-crown ethers regarding both the ionochromism and the cation-binding ability.

cis-Restricted 3-aminopyrazole analogues of combretastatins: synthesis from plant polyalkoxybenzenes and biological evaluation in the cytotoxicity and phenotypic sea urchin embryo assays.

We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl-3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties.

Macrocyclic complexes of palladium(II) with benzothiacrown ethers: synthesis, characterization, and structure of cis and trans isomers.

A series of palladium(II) complexes with nitro- and formylbenzothiacrown-ether derivatives was synthesized. The spatial structure of the complexes was studied by NMR, X-ray diffraction analysis, and quantum chemical calculations (density functional theory). The cavity size and the ligand denticity were found to be crucial factors determining the geometric configuration of the thiacrown-ether complexes.

Synthesis, structure, and properties of supramolecular charge-transfer complexes between bis(18-crown-6)stilbene and ammonioalkyl derivatives of 4,4'-bipyridine and 2,7-diazapyrene.

4,4'-Bipyridine and 2,7-diazapyrene derivatives (A) having two ammonioalkyl N-substituents were synthesized. The complex formation of these compounds with bis(18-crown-6)stilbene (D) was studied by spectrophotometry, cyclic voltammetry, (1)H NMR spectroscopy, and X-ray diffraction analysis. In MeCN, π-donor D and π-acceptors A form supramolecular 1:1 (D·A) and 2:1 (D·A·D) charge-transfer complexes.

Synthetic utilization of polynitroaromatic compounds. 6. Remarkable regioselectivity in nucleophilic displacement of aromatic nitro groups with amines.

5,7-Dinitroquinazoline-4-ones undergo nucleophilic displacement of a nitro group with N-, S-, and O-nucleophiles. In contrast to previously studied dinitro-substituted benzoannulated five- and seven-membered heterocycles (where a high degree of selectivity was observed), these quinazolines mostly yield mixtures of regioisomeric substitution products. At the same time, primary and secondary amines react selectively to afford 5-aminoquinazolones (peri-substitution).

Synthetic utilization of polynitroaromatic compounds. 3. Preparation of substituted dibenz[b,f][1,4]oxazepine-11(10H)-ones from 2,4,6-trinitrobenzoic acid via nucleophilic displacement of nitro groups.

[Reaction: see text]. 1,3-dinitrodibenz[b,f][1,4]oxazepin-11(10H)-one, prepared by intramolecular displacement of nitro group in N-(2-hydroxyphenyl)-2,4,6-trinitrobenzamide, reacts with O- and S-nucleophiles to yield the products of mono- or bis-substitution of the nitro groups. The nitro group in position 3 is displaced first.

Release of nitrosating species in the course of reduction of benzo-1,2,3,4-tetrazine 1,3-dioxides.

[reaction: see text] The reduction of benzo-1,2,3,4-tetrazine 1,3-dioxides (BTDOs) 1 with Na(2)S(2)O(4) or SnCl(2) is suggested to proceed via intermediate N-nitrosobenzotriazoles 3 to afford benzotriazoles 2. The (15)N-labeling experiments exhibit that the N-3 atom of the tetrazine ring is incorporated into the nitroso group of 3 that is ultimately released into solution. It is possible that the biological activity of BTDOs is due to their ability to release nitrosating species, i.