Anti-inflammatory and immunosuppressive effects of the enaminone E121

Asthma is a chronic inflammatory disease of the airways. The treatment of asthma is far from optimal and hence the need for novel therapeutic agents exists. The purpose of this study was to assess the anti-asthma effects of an enaminone, E121, and also its effects on human peripheral blood mononuclear cell proliferation and cytokine release. The effects of E121 were assessed in an ovalbumin-induced model of airway inflammation and airway hyperresponsiveness. In addition, the effects of E121 on phytohemagglutinin (PHA), anti-CD3 monoclonal antibody and lipopolysaccharide (LPS)-induced human peripheral blood mononuclear cell proliferation and cytokine release, respectively, were assessed. Treatment of mice with E121 significantly decreased the ovalbumin-induced increase in airway total cell influx and eosinophil infiltration and this was associated with an inhibition of ovalbumin-induced airway hyperresponsiveness. Moreover, E121 reduced PHA and anti-CD3-induced human peripheral blood mononuclear cell proliferation in vitro. E121 also inhibited PHA, anti-CD3 monoclonal antibody and LPS-induced cytokine release from human peripheral blood mononuclear cell cultures. These findings indicate that E121 exhibits anti-inflammatory and immunosuppressive activities.

X-ray crystallographic and theoretical studies of an anticonvulsant enaminone:methyl 4-(4'-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate

Objective: The aims of this study were to establish the structure of the potent anticonvulsant enaminone methyl 4-(4′-bromophenyl)amino-6-methyl-2- oxocyclohex-3-en-1-oate (E139), and to determine the energetically preferred conformation of the molecule, which is responsible for the biological activity. Materials and Methods: The structure of the molecule was determined by X-ray crystallography. Theoretical ab initio calculations with different basis sets were used to compare the energies of the different enantiomers and to other structurally related compounds. Results: The X-ray crystal structure revealed two independent molecules of E139, both with absolute configuration C11(S), C12(R), and their inverse. Ab initio calculations with the 6-31G, 3-21G and STO-3G basis sets confirmed that the C11(S), C12(R) enantiomer with both substituents equatorial had the lowest energy. Compared to relevant crystal structures, the geometry of the theoretical structures shows a longer C-N and shorter C=O distance with more cyclohexene ring puckering in the isolated molecule. Conclusion: Based on a pharmacophoric model it is suggested that the enaminone system HN-C=C-C=O and the 4-bromophenyl group in E139 are necessary to confer anticonvulsant property that could lead to the design of new and improved anticonvulsant agents. Copyright © 2003 S. Karger AG, Basel.

Síntese de enaminonas

The general term "enaminone" is applied to any compound bearing the conjugated system N-C=C-C=O. Enaminones are typical capto-dative ethylenes, showing particular properties due to pi-electron delocalization. Their reactivity can be predicted by structural patterns of substitution, conformation and configuration, making them versatile synthetic building blocks. In this review, a variety of methods for the synthesis of enaminones is described. The methods were divided into condensation of amines to beta-dicarbonyl compounds, addition of amines to a,b-unsaturated carbonyl compounds, condensation between carbonyl compounds and N-unsaturated functions and other methods, covering the period from 1993 to 2001.

Structural and reactivity analyses of 2-benzylamino-1,4-naphthoquinone by X-ray characterization, electrochemical measurements, and dft single-molecule calculations

This study represents an integrated approach towards understanding the electronic and structural aspects of 2-benzylamino-1,4-naphthalenedione, a representative 2-amino-napfthoquinone. To this end, theoretical calculations performed at the B3PW91/6-31+G(d) level of density functional theory, electrochemical and X-ray structural investigation were employed. Two intramolecular H-bonds and other two intermolecular H-bonds were observed, including non-classical interactions. Cyclic voltammogram (CV) and differential pulse voltammetry (DPV) show two pairs of peaks, being each one a monoelectronic process.

Acoplamento de cloreto de 4-nitrofenildiazônio com nucleófilos alifáticos: experimento integrado de síntese orgânica e cristalografia de raios X

This article describes an undergraduate experiment for the synthesis of p-nitrophenyldiazonium chloride and its coupling with acetylacetone and two enaminones, 4-phenylamino-pent-3-en-2-one and 4-amino-pent-3-en-2-one, in an adaptation of a previously reported synthetic protocol. The azo dyes 4-(E)-phenylamino-3-[(E)-2-(4-nitrophenylazo)]-3-penten-2-one and 4-(E)-amino-3-[(E)-2-(4-nitrophenylazo)]-3-penten-2-one were obtained, and the solid state structure of this latter azo compound was characterized by single crystal X-ray diffraction studies. This two-week integrated laboratory approach involves simple synthetic experiments and microwave chemistry in the organic laboratory plus crystallography analysis, suitable for novice students on undergraduate experimental chemistry courses.

Simple and efficient synthesis of substituted 2-pyrrolidinones, 2-pyrrolones and pyrrolidines from enaminones of Baylis-Hillman derivatives of 3-isoxazolecarbaldehydes

The enaminones, generated from derivatives of appropriately substituted Baylis-Hillman adducts of 3-isoxazolecarbaldehydes undergo intramolecular ring-closure reactions to afford substituted 2-pyrrolidinones, 1,5-dihydro-2-pyrrolones and N-substituted pyrrolidines in good yields.