RESUMO
The syntheses and rat CRF receptor binding affinities of 'retro-pyrazolotriazine' corticotropin-releasing factor (CRF) ligands 4 are reported. Some have high affinity for rat CRF receptors (K(i)< or =10 nM). The data provide additional support for the hypothesis that it is possible to interchange isosteric cores with similar electronic properties in the design of high-affinity CRF receptor ligands, provided the peripheral pharmacophore elements are maintained in the same three-dimensional array.
Assuntos
Pirazóis/química , Receptores de Hormônio Liberador da Corticotropina/efeitos dos fármacos , Triazinas/síntese química , Animais , Sítios de Ligação , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Hormônio Liberador da Corticotropina/química , Hormônio Liberador da Corticotropina/farmacologia , Técnicas In Vitro , Ligantes , Modelos Moleculares , Estrutura Molecular , Ratos , Receptores de Hormônio Liberador da Corticotropina/classificação , Triazinas/farmacologiaRESUMO
Potent, small molecule A beta inhibitors have been prepared that incorporate an alanine core bracketed by an N-terminal arylacetyl group and various C-terminal amino alcohols. The compounds exhibit stereospecific inhibition as demonstrated in an in vitro assay.