We have recently reported a detailed structure-activity relationship study around a wide series of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl) methyl]thiophene derivatives as potent allosteric enhancers of the A1 adenosine receptor. In the current study, we have continued to explore the potential of these molecules by synthesizing of a novel series of analogues that share a common 2-amino-3-(4-chlorobenzoyl)thiophene nucleus. Modifications were focused on varying the nature and the position of electron-withdrawing or electron-releasing groups on the phenyl of an arylpiperazine moiety attached at the 4-position of the thiophene ring by a methylene chain, combined with the presence of small alkyl groups (methyl or ethyl), bromine, or aryl moieties at the thiophene C-5 position. In this series of compounds, substitution at the 5-position had a fundamental effect on activity, with the 5-aryl group contributing additively to the allosteric enhancer activity. The thiophene C-5 aryl derivatives 4ad, 4ak, and 4al were the most active compounds in binding and functional experiments. © 2012 American Chemical Society.

Synthesis and biological evaluation of 2-amino-3-(4-chlorobenzoyl)-4-[(4- arylpiperazin-1-yl)methyl]-5-substituted-thiophenes. Effect of the 5-modification on allosteric enhancer activity at the A1 adenosine receptor

ROMAGNOLI, Romeo;BARALDI, Pier Giovanni;PRETI, Delia;AGHAZADEH TABRIZI, Mojgan;VINCENZI, Fabrizio;BOREA, Pier Andrea;VARANI, Katia
2012

Abstract

We have recently reported a detailed structure-activity relationship study around a wide series of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl) methyl]thiophene derivatives as potent allosteric enhancers of the A1 adenosine receptor. In the current study, we have continued to explore the potential of these molecules by synthesizing of a novel series of analogues that share a common 2-amino-3-(4-chlorobenzoyl)thiophene nucleus. Modifications were focused on varying the nature and the position of electron-withdrawing or electron-releasing groups on the phenyl of an arylpiperazine moiety attached at the 4-position of the thiophene ring by a methylene chain, combined with the presence of small alkyl groups (methyl or ethyl), bromine, or aryl moieties at the thiophene C-5 position. In this series of compounds, substitution at the 5-position had a fundamental effect on activity, with the 5-aryl group contributing additively to the allosteric enhancer activity. The thiophene C-5 aryl derivatives 4ad, 4ak, and 4al were the most active compounds in binding and functional experiments. © 2012 American Chemical Society.
2012
Romagnoli, Romeo; Baraldi, Pier Giovanni; M. D., Carrion; C., Lopez Cara; O., Cruz Lopez; M. K., Salvador; Preti, Delia; AGHAZADEH TABRIZI, Mojgan; Mo...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1696112
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