4-Amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (1) has been found to be an A(2A) versus A(1) selective antagonist (Colotta et al. Arch. Pharm. Pharm. Med. Chem. 1999,332, 39-41). In this paper some novel triazoloquinoxalin-1-ones 4-25 bearing different substituents on the 2-phenyl and/or 4-amino moiety of the parent 4-amino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (3) have been synthesized and tested in radioligand binding assays at bovine A(1) and A(2A) and cloned human A(3) adenosine receptors (AR). Moreover, the binding activities at the above-mentioned AR subtypes of the 1,4-dione parent compounds 26-31 and their 5-N-alkyl derivatives 33-37 were also evaluated. The substituent on the 2-phenyl ring exerted a different effect on AR subtypes, while replacement of a hydrogen atom of the 4-amino group with suitable substituents yielded selective A(1) or A(3) antagonists. Replacement of a hydrogen atom of the 4-NH2 with an acyl group, or replacement of the whole 4-NH2 with a 4-oxo moiety, shifted the binding activity toward the A(3) AR. The binding results allowed elucidation of the structural requirements for the binding of these novel tricyclic derivatives at each receptor subtype. In particular, A(1) and A(2A) binding required the presence of a proton donor group at position-4, while for A(3) affinity the presence of a proton acceptor in this same region was of paramount importance.

1,2,4-Triazolo[4,3-a]quinoxalin-1-one: a versatile tool for the synthesis of potent and selective adenosine receptor antagonists

MARTINI, CLAUDIA;TRINCAVELLI, MARIA LETIZIA;LUCACCHINI, ANTONIO
2000

Abstract

4-Amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (1) has been found to be an A(2A) versus A(1) selective antagonist (Colotta et al. Arch. Pharm. Pharm. Med. Chem. 1999,332, 39-41). In this paper some novel triazoloquinoxalin-1-ones 4-25 bearing different substituents on the 2-phenyl and/or 4-amino moiety of the parent 4-amino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (3) have been synthesized and tested in radioligand binding assays at bovine A(1) and A(2A) and cloned human A(3) adenosine receptors (AR). Moreover, the binding activities at the above-mentioned AR subtypes of the 1,4-dione parent compounds 26-31 and their 5-N-alkyl derivatives 33-37 were also evaluated. The substituent on the 2-phenyl ring exerted a different effect on AR subtypes, while replacement of a hydrogen atom of the 4-amino group with suitable substituents yielded selective A(1) or A(3) antagonists. Replacement of a hydrogen atom of the 4-NH2 with an acyl group, or replacement of the whole 4-NH2 with a 4-oxo moiety, shifted the binding activity toward the A(3) AR. The binding results allowed elucidation of the structural requirements for the binding of these novel tricyclic derivatives at each receptor subtype. In particular, A(1) and A(2A) binding required the presence of a proton donor group at position-4, while for A(3) affinity the presence of a proton acceptor in this same region was of paramount importance.
Colotta, V; Catarzi, D; Varano, F; Cecchi, L; Filacchioni, G; Martini, Claudia; Trincavelli, MARIA LETIZIA; Lucacchini, Antonio
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS 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/11568/205408
 Attenzione

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

Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 78
  • ???jsp.display-item.citation.isi??? 77
social impact