RESUMO
Following the recent disclosure of 3-methyl pyrrole-2,4-dicarboxylic acid 2-propyl ester 4-(1,2,2-trimethyl-propyl) ester, a potent and selective mGluR1 non-competitive antagonist, we report here a detailed exploration of the C-2 position of this scaffold with the preparation of differently substituted amides. Great improvement of the pharmacokinetic properties has been achieved through this exercise.
Assuntos
Ésteres/síntese química , Ésteres/farmacologia , Pirróis/síntese química , Pirróis/farmacologia , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Amidas/síntese química , Amidas/farmacocinética , Animais , Azidas/síntese química , Azidas/farmacocinética , Fenômenos Químicos , Físico-Química , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Ácidos Hidroxâmicos/síntese química , Ácidos Hidroxâmicos/farmacocinética , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Conformação Molecular , Ratos , Solubilidade , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
Following the disclosure of 3-(1,2,2-trimethylpropyl) 4-[3,5-dimethyl-2-propyloxycarbonyl]pyrrolecarboxylate as a potent and selective mGluR1 non-competitive antagonist, the role and the importance of the pyrrole template were investigated. Different aromatic moieties were investigated as possible bio-isosteric replacement of the original scaffold and some of them were shown to be partially able to mimic the properties of the original pyrrole ring.
