RESUMO
Potent and selective antagonists of the adenosine A2A receptor often contain a nitrogen-rich fused-ring heterocyclic core. Replacement of the core with an isomeric ring system has previously been shown to improve target affinity, selectivity, and in vivo activity. This paper describes the preparation, by a novel route, of A2A receptor antagonists containing the [1,2,4]triazolo[1,5-a]pyrazine nucleus, which is isomeric with the [1,2,4]triazolo[1,5-c]pyrimidine core of a series of known A2A antagonists with in vivo activity in animal models of Parkinson's disease.
Assuntos
Antagonistas do Receptor A2 de Adenosina , Pirazinas/síntese química , Animais , Encéfalo/ultraestrutura , Membrana Celular/química , Membrana Celular/metabolismo , Modelos Animais de Doenças , Doença de Parkinson/tratamento farmacológico , Pirazinas/farmacologia , Ensaio Radioligante , Ratos , Relação Estrutura-AtividadeRESUMO
Designed as a new group of planar molecule containing the proposed 2-phenylnaphthalene-type structure, a number of 11H-indolo[3.2-c]quinoline derivatives were synthesized and evaluated biologically. Several compounds were found to possess cytotoxic activity against the growth of human promyelocytic leukemia cells (HL-60), against the small cell lung cancer (SCLC), and showed good response in the National Cancer Institute preclinical antitumor drug discovery 60-cell line panel.