RESUMO
Novel pyrazolo[3,4-b]quinoline α-ketophosphonic and hydroxymethylenebisphosphonic acid compounds were synthesized using different methodologies, starting from 2-chloro-3-formylquinoline 1. New phosphonic acid compounds were obtained as N-1 derivatives with a side chain with 1 or 3 (n = 1 or 3) methylene groups. All phosphonic acid compounds and their corresponding ester and carboxylic acid precursors were fully characterized, and their structures elucidated by spectroscopic data, using NMR techniques and infrared and high-resolution mass spectroscopy. During the process to obtain the N-1 substituted derivative with two methylene groups (n = 2) in the side chain, an unexpected addition-cyclization cascade reaction was observed, involving the phosphonylation of an aromatic ring and the formation of a new six-member lactam ring to afford a tetracyclic ring system. This was an unexpected result since other pyrazolo[3,4-b]quinoline derivatives and all corresponding pyrazolo[3,4-b]pyridine derivatives already prepared, under similar experimental conditions, did not undergo this reaction. This domino reaction occurs with different phosphite reagents but only affords the six-member ring. The spectroscopic data allowed the identification of the new synthesized tetracyclic compounds and the X-ray diffraction data of compound 11 enabled the confirmation of the proposed structures.
RESUMO
A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2)(n)CO2R of different lengths (n = 0-6, 9, 10) are described. Nucleophilic substitution reactions on halo esters (X(CH2)(n)CO2R) by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomer predominates. Basic hydrolysis of the ester derivatives allowed the synthesis of the corresponding indazole carboxylic acids. All compounds were fully characterised by multinuclear NMR and IR spectroscopies, MS spectrometry and elemental analysis; the NMR spectroscopic data were used for structural assignment of the N-1 and N-2 isomers. The molecular structure of indazol-2-yl-acetic acid (5b) was determined by X-ray diffraction, which shows a supramolecular architecture involving O2-H...N1 intermolecular hydrogen bonds.
Assuntos
Ácidos Carboxílicos/química , Ácidos Carboxílicos/síntese química , Ésteres/química , Ésteres/síntese química , Indazóis/química , Indazóis/síntese química , Ácido Acético/química , Isótopos de Carbono , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , EstereoisomerismoRESUMO
The in vitro antimicrobial activity of a new series of synthetic fluorine-substituted triaryl alcohols against the human pathogens Staphylococcus aureus, Escherichia coli, and Candida albicans was studied with the aim of overcoming multiple drug resistance and improving the clinical usefulness of antimicrobial drugs. The nature and positions of substituents attached to aromatic rings, as well as their electronegativities and sizes, seem to affect the preferred molecular conformations and, hence, the binding of the compounds to the corresponding cell receptors.