RESUMO
7-Arylsulfonyl substituted benzofuropiperidine was discovered as a novel scaffold for 5HT(6) receptor antagonists. Optimization by substitution at C-1 position led to identification of selective, orally bioavailable, brain penetrant antagonists with reduced hERG liability. An advanced analog tested in rat social recognition model showed significant activity suggesting potential utility in the enhancement of short-term memory.
Assuntos
Benzofuranos/química , Piperidinas/química , Receptores de Serotonina/química , Antagonistas da Serotonina/farmacologia , Animais , Encéfalo/embriologia , Encéfalo/metabolismo , Canal de Potássio ERG1 , Canais de Potássio Éter-A-Go-Go/metabolismo , Humanos , Concentração Inibidora 50 , Cinética , Memória de Curto Prazo/efeitos dos fármacos , Modelos Químicos , Ratos , Esquizofrenia/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
The elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression.
Assuntos
Proteína-Tirosina Quinases de Adesão Focal/química , Janus Quinase 2/química , Inibidores de Proteínas Quinases/farmacologia , Animais , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Progressão da Doença , Desenho de Fármacos , Humanos , Concentração Inibidora 50 , Camundongos , Modelos Químicos , Mutação , Neoplasias/genética , Neoplasias/patologia , Inibidores de Proteínas Quinases/síntese química , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fatores de TempoRESUMO
A unique porcine circovirus type 2 capsid protein (ORF2) sequence was detected in swine samples submitted to the Iowa State University Veterinary Diagnostic Laboratory. The complete genome sequences of four viruses, one from Mexico and three from the United States, were determined to further characterize this novel PCV2 genotype.