Síntesis, análisis conformacional y reactividad de inmunosupresores potenciales referibles al oxisurano

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química. Fecha de lectura: 21-11-198

Excitotoxic profile of LY339434, a GluR5 agonist, in cultured murine cortical neurons

The neurotoxic profile of (2S,4R,6E)-2-amino-4-carboxy-7-(2-naphthyl)hept-6-enoic acid (LY339434), a low-affinity kainate receptor subtype 5 (GluR5) agonist at recombinant human glutamate receptors, was evaluated to investigate the involvement of GluR5 in excitotoxic neuronal death. Murine cortical neurons were exposed to treatments for 24 h and assessed by a cell viability assay and phase-contrast microscopy. LY339434 (1-1000 mu M) caused a concentration-dependent decrease in cell viability (EC50 = 11.4+/-1.2 mu M) that was only attenuated by (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801, 10 mu M), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 mu M) or 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466, 20 mu M). Labeling with nucleic acid binding dyes revealed that LY339434 induced few apoptotic-like characteristics. These findings indicate that in cultured murine cortical neurons, LY339434 acts predominantly through N-methyl-D-aspartate (NMDA) receptors rather than GluR5 to effect neuronal death that is rapid and involves predominantly necrosis rather than morphological apoptosis. (C) 2000 Elsevier Science B.V. All rights reserved

General method for the synthesis of 5-arylpyrrole-2-carboxylic acids

5-Arylpyrrole-2-carboxylic acids are prepared by DDQ oxidative aromatization of the corresponding ethyl 2-aryl-DELTA1-pyrroline-5-carboxylate followed by basic hydrolysis.This research was conducted under the Spanish FARMA II programme (Ministerio de lndustria). J. V. is grateful to Lilly,S. A. for a fellowship