RESUMO
A series of pyrazinones were prepared and evaluated as potential CRF(1)R PET imaging agents. Optimization of their CRF(1)R binding potencies and octanol-phosphate buffer phase distribution coefficients are discussed herein.
Assuntos
Tomografia por Emissão de Pósitrons , Pirazinas/farmacologia , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Animais , Encéfalo , Humanos , Estrutura Molecular , Pirazinas/química , Ratos , Receptores de Hormônio Liberador da Corticotropina/químicaRESUMO
Based on a favorable balance between CRF-R1 affinity, lipophilicity and metabolic stability, compound 10 was evaluated for potential development as PET radioligand. Compound [(18)F]10 was prepared with high radiochemical purity and showed promising binding properties in rat brain imaging experiments.
Assuntos
Compostos de Anilina/química , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Pirazinas/química , Pirazóis/química , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Radioisótopos de Flúor/sangue , Imageamento Tridimensional , Estrutura Molecular , Pirazóis/metabolismo , Ratos , Distribuição TecidualRESUMO
A series of N-fluoroalkyl-8-(6-methoxy-2-methylpyridin-3-yl)-2,7-dimethyl-N-alkylpyrazolo[1,5-a][1,3,5]triazin-4-amines were prepared and evaluated as potential CRF(1)R PET imaging agents. Optimization of their CRF(1)R binding potencies and octanol-phosphate buffer phase distribution coefficients resulted in discovery of analog 7e (IC(50)=6.5 nM, logD=3.5).