A number of 4-oxo-substituted 1,2,4-triazolo[1,5-a]quinoxaline derivatives bearing at position-2 the claimed (hetero)aryl moiety (compounds 1-15) but also a carboxylate group (16-28, 32- 36) or a hydrogen atom (29-31) were designed as human A3 (hA3) adenosine receptor (AR) antagonists. This study produced some interesting compounds and among them the 2-(4- methoxyphenyl)-1,2,4-triazolo[1,5-a]quinoxalin-4-one (8), which can be considered one of the most potent and selective hA3 adenosine receptor antagonists reported till now. Moreover, as a new finding, replacement of the classical 2-(hetero)aryl moiety with a 2-carboxylate function (compounds 16-28 and 32-36) maintained good hA3 AR binding activity but, most importantly and interestingly, produced a large increase in hA3 versus hA1 selectivity. A receptor-based SAR analysis provided new interesting insights about the steric and electrostatic requirements that are important for the anchoring of these derivatives at the hA3 receptor recognition site, thus highlighting the versatility of the triazoloquinoxaline scaffold for obtaining potent and selective hA3 AR antagonists.

1,2,4-Triazolo[1,5-a]quinoxaline as a versatile tool for the design of selective human A3 adenosine receptor antagonists: synthesis, biological evaluation and molecular modeling studies of 2-(hetero)aryl- and 2-carboxy-substituted derivatives / D. CATARZI; V. COLOTTA; F. VARANO; O. LENZI; G. FILACCHIONI; L. TRINCAVELLI; C. MARTINI; C. MONOPOLI; S. MORO. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 48(2005), pp. 7932-7945.

1,2,4-Triazolo[1,5-a]quinoxaline as a versatile tool for the design of selective human A3 adenosine receptor antagonists: synthesis, biological evaluation and molecular modeling studies of 2-(hetero)aryl- and 2-carboxy-substituted derivatives.

CATARZI, DANIELA;COLOTTA, VITTORIA;VARANO, FLAVIA;FILACCHIONI, GUIDO;
2005

Abstract

A number of 4-oxo-substituted 1,2,4-triazolo[1,5-a]quinoxaline derivatives bearing at position-2 the claimed (hetero)aryl moiety (compounds 1-15) but also a carboxylate group (16-28, 32- 36) or a hydrogen atom (29-31) were designed as human A3 (hA3) adenosine receptor (AR) antagonists. This study produced some interesting compounds and among them the 2-(4- methoxyphenyl)-1,2,4-triazolo[1,5-a]quinoxalin-4-one (8), which can be considered one of the most potent and selective hA3 adenosine receptor antagonists reported till now. Moreover, as a new finding, replacement of the classical 2-(hetero)aryl moiety with a 2-carboxylate function (compounds 16-28 and 32-36) maintained good hA3 AR binding activity but, most importantly and interestingly, produced a large increase in hA3 versus hA1 selectivity. A receptor-based SAR analysis provided new interesting insights about the steric and electrostatic requirements that are important for the anchoring of these derivatives at the hA3 receptor recognition site, thus highlighting the versatility of the triazoloquinoxaline scaffold for obtaining potent and selective hA3 AR antagonists.
48
7932
7945
Goal 3: Good health and well-being
D. CATARZI; V. COLOTTA; F. VARANO; O. LENZI; G. FILACCHIONI; L. TRINCAVELLI; C. MARTINI; C. MONOPOLI; S. MORO
File in questo prodotto:
File Dimensione Formato  
Catarzijmc_05_48_7932.pdf

Accesso chiuso

Tipologia: Altro
Licenza: DRM non definito
Dimensione 741.12 kB
Formato Adobe PDF
741.12 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in FLORE 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: http://hdl.handle.net/2158/310007
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 53
  • ???jsp.display-item.citation.isi??? 52
social impact