RESUMO
We describe herein the discovery and development of a series of 4-arylthieno[3,2-d]pyrimidines which are potent adenosine A(2A) receptor antagonists. These novel compounds show high degrees of selectivity against the human A(1), A(2B) and A(3) receptor sub-types. Moreover, a number of these compounds show promising activity in vivo, suggesting potential utility in the treatment of Parkinson's disease.
Assuntos
Antagonistas do Receptor A2 de Adenosina , Antiparkinsonianos/uso terapêutico , Desenho de Fármacos , Transtornos Parkinsonianos/tratamento farmacológico , Pirimidinas/uso terapêutico , Antagonistas do Receptor A1 de Adenosina , Antagonistas do Receptor A3 de Adenosina , Antiparkinsonianos/síntese química , Humanos , Modelos Químicos , Pirimidinas/síntese química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A series of pyrazolo[3,4-d]pyrimidine, pyrrolo[2,3-d]pyrimidine and 6-arylpurine adenosine A(2A) antagonists is described. Many examples were highly selective against the human A(1) receptor sub-type and were active in an in vivo model of Parkinson's disease.
Assuntos
Antagonistas do Receptor A2 de Adenosina , Antiparkinsonianos/uso terapêutico , Desenho de Fármacos , Transtornos Parkinsonianos/tratamento farmacológico , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Antagonistas do Receptor A1 de Adenosina , Antiparkinsonianos/síntese química , Humanos , Modelos Químicos , Purinas/síntese química , Pirazóis/síntese química , Pirimidinas/síntese química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
The (-)-(11R,2'S)-enantiomer of the antimalarial drug mefloquine has been found to be a reasonably potent and moderately selective adenosine A(2A) receptor antagonist. Further investigation of this compound has led to the discovery of a series of keto-aryl thieno[3,2-d]pyrimidine derivatives, which are potent and selective antagonists of the adenosine A(2A) receptor. These derivatives show selectivity against the A(1) receptor. Furthermore, some of these compounds have been shown to have in vivo activity in a commonly used model, suggesting the potential for the treatment of Parkinson's disease.