Mariano A. Pereira

Studies towards the identification of putative bioactive conformation of potent vasodilator arylidene N-acylhydrazone derivatives

In this report we disclose the synthesis, vasodilatory activity, and identification of bioactive conformation of new N-acylhydrazone and N-methyl-N-acylhydrazone derivatives, structurally designed by bioisosteric replacements of previously described cardioactive compounds LASSBio-294 and its N-methyl derivative LASSBio-785. Some of these novel derivatives presented improved vasorelaxant properties, being new cardiovascular drug candidates.

Synthesis and structural study of arylidene thiazolidine and benzothiazine compounds

Synthesis and physico-chemical properties of some 5-arylidene-3-(2-biphenyl-4-yl-2-oxo-ethyl)- and 3-(4-bromo-benzyl)-4-thioxo-thiazolidin-2-ones, 5-arylidene-3-(4-chloro-benzyl)-4-thioxo- and 4-oxo-thiazolidin-2-ones and 2-arylidene-6-benzoyl-amino- or 6-amino-4 H -benzo[1,4]thiazin-3-ones are described. These arylidene thiazolidines and benzothiazines compounds were prepared by Knoevenagel condensation with benzaldehydes.

The influence of electronic and steric effects in the structure–activity relationship (SAR) study of quinone compounds with biological activity against Trypanosoma cruzi

Abstract A set of 14 quinone compounds with anti-trypanocidal activity was studied by using the AM1 semi-empirical method in order to calculate atomic and molecular properties (variables or descriptors) to be correlated to the biological activity. Principal component analysis (PCA), hierarchical cluster analysis (HCA), stepwise discriminant analysis (SDA) and the K th nearest neighbor (KNN) method were employed to obtain possible relationships between the calculated descriptors and the biological activity studied and to predict the anti-trypanocidal activity of new quinone compounds from a prediction set. The atomic and molecular descriptors responsible for the separation between the active and inactive compounds were: total energy ( E T ), polarizability ( α ) and the charge on the R 1 atom ( Q 4 ). These descriptors give information on the kind of interaction that can occur between the compounds and the biological receptor. The prediction study was done with a set of three new compounds by using the PCA, HCA, SDA and KNN methods and two of them were predicted as active against T. cruzi .

Nitrooxyquinones: synthesis, X-ray diffraction and electrochemical studies

Abstract 2-Methyl-3-(nitrooxymethyl)-[1,4]-naphthoquinone and 2-(nitrooxymethyl)-[9,10]-anthraquinone, the first representatives of quinone-derived organic nitrates, potential hybrid drugs, were obtained and characterized through X-ray diffraction. Voltammetric studies showed that reductive elimination occurs, after quinone reduction. The NO3− release, leading to electrogenerated quinonemethide, would suggest a quinone-driven biological activity.

Conventional and microwave-assisted reaction of N-hydroxymethylphthalimide with arylamines: synthesis of N-(arylaminomethyl)-phthalimides

An efficient and easy synthesis of compounds: 2-Phenylaminomethyl-isoindole-1,3-dione (5a), 2-[(2-Clorophenylamino)methyl]-isoindole-1,3-dione (5b), 2-[(3-Clorophenylamino)methyl]-isoindole-1,3-dione (5c), 2-[(4-Clorophenylamino)methyl)-isoindole-1,3-dione (5d), 2-[(2-Fluorophenylamino)methyl]-isoindole-1,3-dione (5e), 2-[(3-fluorophenylamino)methyl]-isoindole-1,3-dione (5f), 2-[(4-Fluorophenylamino)methyl]-isoindole-1,3-dione (5g), 2-[(2-Nitrophenylamino)methyl]-isoindole-1,3-dione (5h), 2-[(3-Nitrophenylamino)methyl]-isoindole-1,3-dione (5i), 2-[(4-Nitrophenylamino)methyl]-isoindole-1,3-dione (5j), 2-[1H-(1,2,4)Triazol-3-yl-aminomethyl)-isoindole-1,3-dione (5k) and 2-([1,2,4]-Triazole-4-yl-aminomethyl)-isoindole-1,3-dione (5l), is described. The general synthesis procedure starts from N-hydroxymethylphthalimide 3 and aryl- and [1,2,4-triazol-3- and 4-yl]-amines 4a-l by conventional and solvent-free microwave-mediated. The reaction of 3 with 4l turned out to be a very rapid and high-yielding one. A comparison of these two methods has been made. Three probable mechanisms of formation of N-(arylaminomethyl)-phthalimides (one in the solution phase and two in the microwave-accelerated conditions are proposed. Crystallographic analyses of 5d furnished the correct conformation of this molecule. Ab initio molecular orbital calculations of 5d using 6-31G* basis set were performed and the results were comparable to the X-ray data.

Synthesis in Water and Antimicrobial Activity of 5-Trichloromethyl-4,5-dihydroisoxazoles

Abstract Two series of 5-trichloromethylisoxazoles were synthesized from the cyclocondensation of 1,1,1-trichloro-4-methoxy-3-alken-2-ones [Cl3CC(O)C(R2) = C(R1)OMe, where R1 = H, Me, Et, Pr, iso-Pr, cyclo-Pr, Bu, terc-Bu, CH2Br, CHBr2, CH(Me)SMe, (CH2)2Ph, and Ph, and R2 = H; R1 = H and R2 = Me and Et; R1 and R2 = -(CH2)4- and -(CH2)5-; and R1 = Et and Ph and R2 = Me] with hydroxylamine hydrochloride through a rapid one-pot reaction in water. The 5-trichloromethyl-4,5-dihydroisoxazoles were aromatized by reaction with concentrated sulfuric acid to obtain the respective 5-trichloromethylisoxazoles. Their structures were confirmed by elemental analysis, 1H/13C nuclear magnetic resonance, and electron impact mass spectroscopy. Crystal structure analysis for 5-triclhoromethyl-5-hydroxy-3-propyl-4,5-dihydroisoxazole (2d) and 5-trichloromethyl-5-hydroxy-3,4-hexamethylene-4,5-dihydroisoxazole (2o) is presented. The antimicrobial activities of the 5-trichloromethyl-4,5-dihydroisoxazole derivatives were examined using the standard twofold dilution method against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and yeasts (Candida spp. and Cryptococcus neoformans). All of the tested 5-trichloromethyldihydroisoxazoles exhibited antibacterial and antifungal activities at the tested concentrations. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communications® to view the free supplemental file. GRAPHICAL ABSTRACT

trans-5,6-Diphenyl­perhydro­pyran-2,4-dione

In the title compound, C17H14O3, the pyran ring adopts a boat conformation and the dihedral angle between the aromatic ring planes is 59.1 (1)°. In the crystal structure intermolecular C—H⋯O hydrogen bonds and C—H⋯π interactions link the molecules.

3-Bromo-β-lapachone

In the title compound, C15H13BrO3, the benzo and quinone rings are planar, while the heterocycle is in a distorted half-chair conformation.

Synthesis, Structure, and Cyclocondensation of the 4,4,4-Trifluoro-3,3-dihydroxy-2-methyl-1-(thien-2-yl)-1-butanone with Hydroxylamine and Hydrazine

The synthesis of 4,4,4-trifluoro-3,3-dihydroxy-2-methyl-1-(thien-2-yl)butan-1-one (3) through acylation of 1,1-dimethoxy-1-(thien-2-yl)propane (1) with trifluoroacetic anhydride and its reactions with hydroxylamine and hydrazine was investigated. X-ray structural analysis of new trifluoromethyl-substituted dielectrophile 3 revealed that this hydrate exists as a racemate with inter- and intramolecular O-H·O bonds. The crystal structure shows alignment along axis b of pair molecules with the same configuration of the O2-H·O1 bond. For 5(3)-trifluoromethyl-4-methyl-3(5)-(thien-2-yl)-1H-pyrazole (4), obtained via cyclocondensation of precursor 2 and hydrazine hydrochloride, X-ray structural analysis indicated that its rings are almost planar (torsion angle N2-C5-C6-C7–5.4°) and that S1 at the thienyl moiety is anti-periplanar to N2 (torsion angle N2-C5-C6-S1 176.01); no disorder effect was observed for the thienyl ring.