A new series of N(6)-[(hetero)aryl/(cyclo)alkyl-carbamoyl-methoxy-phenyl]-(2-chloro)-5'-N-ethylcarboxamido-adenosines (24-43) has been synthesised and tested in binding assays at hA(1), hA(2A) and hA(3) adenosine receptors, and in a functional assay at the hA(2B) subtype. The examined compounds displayed high potency in activating A(2B) receptors with good selectivity versus A(2A) subtypes. The introduction of an unsubstituted 4-[(phenylcarbamoyl)-methoxy]-phenyl chain at the N(6) position of 5'-N-ethylcarboxamido-adenosine led us to the recognition of compound 24 as a full agonist displaying the highest efficacy of the series (EC(50) hA(2B)=7.3 nM). These compounds represent the first report about adenosine-related structures capable of activating hA(2B) subtype in the low nanomolar range.

N-6-[(Hetero)aryl/(cyclo)alkyl-carbamoyi-methoxy-phenyl]-(2chloro)-5 '-N-ethylearboxamido-adenosines: The first example of adenosine-related structures with potent agonist activity at the human A(2B) adenosine receptor

BARALDI, Pier Giovanni;PRETI, Delia;AGHAZADEH TABRIZI, Mojgan;FRUTTAROLO, Francesca;SAPONARO, Giulia;BARALDI, Stefania;ROMAGNOLI, Romeo;GESSI, Stefania;VARANI, Katia;BOREA, Pier Andrea
2007

Abstract

A new series of N(6)-[(hetero)aryl/(cyclo)alkyl-carbamoyl-methoxy-phenyl]-(2-chloro)-5'-N-ethylcarboxamido-adenosines (24-43) has been synthesised and tested in binding assays at hA(1), hA(2A) and hA(3) adenosine receptors, and in a functional assay at the hA(2B) subtype. The examined compounds displayed high potency in activating A(2B) receptors with good selectivity versus A(2A) subtypes. The introduction of an unsubstituted 4-[(phenylcarbamoyl)-methoxy]-phenyl chain at the N(6) position of 5'-N-ethylcarboxamido-adenosine led us to the recognition of compound 24 as a full agonist displaying the highest efficacy of the series (EC(50) hA(2B)=7.3 nM). These compounds represent the first report about adenosine-related structures capable of activating hA(2B) subtype in the low nanomolar range.
2007
Baraldi, Pier Giovanni; Preti, Delia; AGHAZADEH TABRIZI, Mojgan; Fruttarolo, Francesca; Saponaro, Giulia; Baraldi, Stefania; Romagnoli, Romeo; Moorman, Ar; Gessi, Stefania; Varani, Katia; Borea, Pier Andrea
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/470071
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 66
  • ???jsp.display-item.citation.isi??? 61
social impact