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2-Aryladenine derivatives as a potent scaffold for adenosine receptor antagonists: The 6-Morpholino derivatives

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Detalhes bibliográficos
Resumo:A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A<inf>1</inf>, A<inf>2A</inf>, A<inf>2B</inf>, and A<inf>3</inf> adenosine receptor subtypes. Eleven purines showed potent antagonism at A<inf>1</inf>, A<inf>3</inf>, dual A<inf>1</inf>/A<inf>2A</inf>, A<inf>1</inf>/A<inf>2B</inf>, or A<inf>1</inf>/A<inf>3</inf> adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity relationships were made for this group of new compounds. The 9-methylpurine derivatives were generally less potent but more selective, and the 9H-purine derivatives were more potent but less selective. These compounds can be an important source of new biochemical tools and/or pharmacological drugs.
Autores principais:Areias, Filipe
Outros Autores:Correia, Carla; Rocha, Ashly; Teixeira, Sofia; Castro, Marián; Brea, Jose; Hu, Huabin; Carlsson, Jens; Loza, Maria I.; Proença, M. Fernanda R. P.; Carvalho, M. Alice
Assunto:2-arylpurine derivatives adenine derivatives adenosine receptor antagonists G protein-coupled receptors structure-activity relationship
Ano:2024
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo:A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A<inf>1</inf>, A<inf>2A</inf>, A<inf>2B</inf>, and A<inf>3</inf> adenosine receptor subtypes. Eleven purines showed potent antagonism at A<inf>1</inf>, A<inf>3</inf>, dual A<inf>1</inf>/A<inf>2A</inf>, A<inf>1</inf>/A<inf>2B</inf>, or A<inf>1</inf>/A<inf>3</inf> adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity relationships were made for this group of new compounds. The 9-methylpurine derivatives were generally less potent but more selective, and the 9H-purine derivatives were more potent but less selective. These compounds can be an important source of new biochemical tools and/or pharmacological drugs.

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