Evaluation of the toxicity of 5-aryl-2-aminoimidazole-based biofilm inhibitors against eukaryotic cell lines, bone cells and the nematode Caenorhabditis elegans.

Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number of tumor cell lines (L1210, CEM and HeLa).

Microwave-assisted one-pot synthesis and anti-biofilm activity of 2-amino-1H-imidazole/triazole conjugates.

A microwave-assisted protocol was developed for the construction of 2-amino-1H-imidazole/triazole conjugates starting from the previously described 2-hydroxy-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-4-ium salts. The process involves a one-pot hydrazinolysis/Dimroth-rearrangement of these salts followed by a ligand-free copper nanoparticle-catalyzed azide-alkyne Huisgen cycloaddition. The 2-amino-1H-imidazole/triazole conjugates showed moderate to high preventive activity against biofilms of S.

Synthesis of differentially substituted 2-aminoimidazolidines via a microwave-assisted tandem Staudinger/aza-Wittig cyclization.

A new route for the construction of 2-aminoimidazolidines including analogues of the α2 adrenergic agonist drug clonidine is elaborated. The key step is an intramolecular microwave-assisted Staudinger/aza-Wittig cyclization of an in situ generated urea intermediate (formed by the reaction of β-amino azide and isocyanate) upon treatment with Bu3P or polymer-supported phosphine reagent, allowing the introduction of various substituents at the N1 and the 2-amino function. Furthermore, a useful one-pot Staudinger/aza-Wittig/Buchwald-Hartwig protocol leading to bicyclic guanidines has been elaborated.

Synthesis of symmetric 1,4-diamino-2-butynes via a Cu(I)-catalyzed one-pot A3-coupling/decarboxylative coupling of a propiolic acid, an aldehyde, and an amine.

A novel microwave-assisted approach for the one-pot Cu(I)-catalyzed A(3)-coupling/decarboxylative coupling (PA(2)-coupling) of a propiolic acid, an aldehyde, and an amine, resulting in the formation of diversely substituted 1,4-diamino-2-butynes,is described. It is noteworthy that this new multicomponent coupling provides an efficient access to introduce alkyl and aryl group at the 1,4-position of the 1,4-diamino-2-butynes.

Regioselective Cu(I)-catalyzed tandem A3-coupling/decarboxylative coupling to 3-amino-1,4-enynes.

An efficient and novel copper-mediated protocol for the synthesis of 3-amino-1,4-enynes from glyoxylic acid, an amine, and an alkyne was developed. This new reaction involving two sequential C-C bond formations is air and moisture tolerant and proceeds via a tandem A(3)-coupling and a selective decarboxylative coupling.

Microwave-assisted decarboxylative three-component coupling of a 2-oxoacetic acid, an amine, and an alkyne.

A novel and efficient microwave-assisted decarboxylative three-component coupling of a 2-oxoacetic acid, an amine, and an alkyne (OA(2)-coulpling) has been developed. This new multicomponent coupling constitutes an efficient approach for the synthesis of polysubstituted propargylamines in the presence of a catalytic amount of copper(I) catalyst.

Tetrasubstituted 2-imidazolones via Ag(I)-catalyzed cycloisomerization of propargylic ureas.

A one-pot protocol based on a Ag(I)-catalyzed cycloisomerization of propargylic ureas, derived from secondary propargylamines and isocyanates, was developed for the generation of the 2-imidazolone core.

Structure-activity relationship of 2-hydroxy-2-aryl-2,3-dihydro-imidazo[1,2-a]pyrimidinium salts and 2N-substituted 4(5)-aryl-2-amino-1H-imidazoles as inhibitors of biofilm formation by Salmonella Typhimurium and Pseudomonas aeruginosa.

A library of 80 1-substituted 2-hydroxy-2-aryl-2,3-dihydro-imidazo[1,2-a]pyrimidinium salts and 54 2N-substituted 4(5)-aryl-2-amino-1H-imidazoles was synthesized and tested for the antagonistic effect against biofilm formation by Salmonella Typhimurium and Pseudomonas aeruginosa. The nature of the substituent at the 1-position of the salts was found to have a major effect on their biofilm inhibitory activity. Salts with an intermediate length n-alkyl or cyclo-alkyl chain (C7-C10) substituted at the 1-position in general prevented the biofilm formation of both species at low micromolar concentrations, while salts with a shorter n-alkyl or cyclo-alkyl chain (C1-C5) or longer n-alkyl chain (C11-C14) were much less potent.

An expeditious route toward pyrazine-containing nucleoside analogues.

An improved and convenient methodology for the synthesis of asymmetrically substituted pyrazines starting from 3,5-dichloropyrazin-2(1H)-ones has been elaborated. Several nucleoside analogues have been synthesized containing the pyrazine core as the organic base coupled with the sugar via a triazole linkage. The beneficial effect of microwave irradiation throughout the sequence has been demonstrated.

Diversity-oriented synthesis of dibenzoazocines and dibenzoazepines via a microwave-assisted intramolecular A(3)-coupling reaction.

An unprecedented, diversity-oriented strategy for the generation of 6,7-dihydro-5H-dibenzo[c,e]azepines and 5,6,7,8-tetrahydrodibenzo[c,e]azocines by a microwave-assisted copper-catalyzed intramolecular A(3)-coupling reaction is presented.

Microwave-assisted synthesis of a novel class of imidazolylthiazolidin-4-ones and evaluation of its biological activities.

The synthesis and biological activity of a hitherto unknown class of compounds, the imidazolylthiazolidin-4-ones, are described. A two-step procedure has been elaborated starting from our previously described 2-aminoimidazoles. The application of microwave irradiation has been proven to be beneficial for the condensation of the imine with mercaptoacetic acid leading to the formation of imidazolylthiazolidin-4-ones.

A divergent synthesis of substituted 2-aminoimidazoles from 2-aminopyrimidines.

A new divergent and efficient synthesis of substituted 2-aminoimidazoles 5 and 6 has been developed starting from the readily available 2-aminopyrimidines 1 and alpha-bromocarbonyl compounds 2, using conventional heating or microwave irradiation. Thus, the cleavage of 1,2,3-substituted imidazo[1,2-a]pyrimidin-1-ium salts 4 with hydrazine or secondary amines led to 1,4,5-trisubstituted 2-aminoimidazoles 5, when the hydrazinolysis of 2-hydroxy-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-4-ium salts 3, followed by a novel Dimroth-type rearrangement, resulted in formation of 2-amino-1H-imidazoles 6. The relevant pathway of transformations was identified by characterization of the intermediates.

A new colorimetric test for solid-phase amines and thiols.

A new, efficient, sensitive, and reliable color test for the visual detection of resin-bound primary and secondary amines is described. The reaction between amines and 1-methyl-2-(4'-nitrophenyl)-imidazo[1,2- a]pyrimidinium perchlorate (DESC) provides the "on-bead generated" colored stable intermediate azadiene. The developed protocols allow detection of resin-bound primary amines in the presence of secondary amines.

Transition metal-catalyzed orthogonal solid-phase decoration of the 2(1H)-pyrazinone scaffold using a sulfur linker.

A new transition metal-catalyzed orthogonal solid-phase protocol for the synthesis of highly substituted 2(1H)-pyrazinones was developed, on the basis of Chan-Lam arylation and Liebeskind-Srogl cross-coupling reactions. This strategy opens the way for the generation of small libraries of 2(1H)-pyrazinone analogues for biological screening.

Efficient one-pot, two-step, microwave-assisted procedure for the synthesis of polysubstituted 2-aminoimidazoles.

A microwave-assisted, one-pot, two-step protocol was developed for the construction of polysubstituted 2-aminoimidazoles. This process involves the sequential formation of imidazo[1,2-a]pyrimidinium salts from readily available 2-aminopyrimidines and alpha-bromocarbonyl compounds, followed by opening of the pyrimidine ring with hydrazine. [reaction: see text]

The application of "click chemistry" for the decoration of 2(1H)-pyrazinone scaffold: generation of templates.

The "click chemistry" approach has been explored on the 2-(1H)-pyrazinone scaffold for the generation of pharmacologically interesting heterocyclic moieties. Huisgen 1,3-dipolar cycloaddition has been evaluated as the key step for the construction of the 1,2,3-triazole ring at the C-3 position of 2-(1H)-pyrazinones. Two different pathways have been successfully evaluated: (1) via C-C or C-O linkage of the acetylenic part to the C-3 position of the 2-(1H)-pyrazinone scaffold or (2) via azide introduction in the C-3 position.