In this paper we report the synthesis and biological evaluation of a new class of 2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-4-ones as A 3 adenosine receptor antagonists. We designed a new route based on the Kira-Vilsmeier reaction for the synthesis of this class of compounds. Some of the synthesized compounds showed A 3 adenosine receptor affinity in the nanomolar range and good selectivity as evaluated in radioligand binding assays at human (h) A1, A 2A, A 2B, and A 3 adenosine receptor subtypes. We introduced several substituents on the 2-phenyl ring. In particular substitution at the 4-position by methyl, methoxy, and chlorine gave optimal activity and selectivity 6c (K ihA 1, A 2A> 1000 nM, EC 50hA 2B> 1000 nM, K ihA 3 = 9 nM), 6d (K ihA 1, A 2A> 1000 nM, EC 50hA 2B> 1000 nM, K ihA 3 = 16 nM), 6b (K ihA 1, A 2A > 1000 nM, EC 50-hA 2B> 1000 nM, K ihA 3 = 19 nM). In conclusion, the 2-phenyl-2,5-dihydro- pyrazolo[4,3-c]quinolin-4-one derivatives described herein represent a new family of in vitro selective antagonists for the adenosine A 3 receptor. © 2005 American Chemical Society.

New 2-arylpyrazolo[4,3-c]quinoline derivatives as potent and selective human A(3) adenosine receptor antagonists

BARALDI, Pier Giovanni;AGHAZADEH TABRIZI, Mojgan;PRETI, Delia;BOVERO, Andrea;FRUTTAROLO, Francesca;ROMAGNOLI, Romeo;VARANI, Katia;BOREA, Pier Andrea
2005

Abstract

In this paper we report the synthesis and biological evaluation of a new class of 2-phenyl-2,5-dihydro-pyrazolo[4,3-c]quinolin-4-ones as A 3 adenosine receptor antagonists. We designed a new route based on the Kira-Vilsmeier reaction for the synthesis of this class of compounds. Some of the synthesized compounds showed A 3 adenosine receptor affinity in the nanomolar range and good selectivity as evaluated in radioligand binding assays at human (h) A1, A 2A, A 2B, and A 3 adenosine receptor subtypes. We introduced several substituents on the 2-phenyl ring. In particular substitution at the 4-position by methyl, methoxy, and chlorine gave optimal activity and selectivity 6c (K ihA 1, A 2A> 1000 nM, EC 50hA 2B> 1000 nM, K ihA 3 = 9 nM), 6d (K ihA 1, A 2A> 1000 nM, EC 50hA 2B> 1000 nM, K ihA 3 = 16 nM), 6b (K ihA 1, A 2A > 1000 nM, EC 50-hA 2B> 1000 nM, K ihA 3 = 19 nM). In conclusion, the 2-phenyl-2,5-dihydro- pyrazolo[4,3-c]quinolin-4-one derivatives described herein represent a new family of in vitro selective antagonists for the adenosine A 3 receptor. © 2005 American Chemical Society.
2005
Baraldi, Pier Giovanni; AGHAZADEH TABRIZI, Mojgan; Preti, Delia; Bovero, Andrea; Fruttarolo, Francesca; Romagnoli, Romeo; Zaid, Na; Moorman, Ar; Varan...espandi
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/11392/516943
 Attenzione

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

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 68
  • ???jsp.display-item.citation.isi??? 64
social impact