A structural investigation on some 4-amido-2-phenyl-1,2-dihydro-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives, designed as human A3 adenosine receptor (hA3 AR) antagonists, is described. In the new derivatives, some acyl residues with different steric bulk were introduced on the 4-amino group, and their combination with the 4-methoxy group on the 2-phenyl moiety, and/or the 6-nitro/6-amino substituent on the fused benzo ring, was also evaluated. Most of the new derivatives were potent and selective hA3 AR antagonists. SAR analysis showed that hindering and lipophilic acyl moieties not only are well tolerated but even ameliorate the hA3 affinity. Interestingly, the 4-methoxy substituent on the appended 2-phenyl moiety, as well as the 6-amino group, always exerted a positive effect, shifting the affinity toward the hA3 receptor subtype. In contrast, the 6-nitro substituent exerted a variable effect. An intensive molecular modeling investigation was performed to rationalize the experimental SAR findings.

4-Amido-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-ones as New Potent and Selective Human A3 Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation and Ligand-Receptor Modeling Studies / O. LENZI; V. COLOTTA; D. CATARZI; F.VARANO; G. FILACCHIONI; C. MARTINI; L. TRINCAVELLI; OSELE CIAMPI; KATIA VARANI; FEDERICO MARIGHETTI; ERIKA MORIZZO; STEFANO MORO. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 49:(2006), pp. 3916-3925.

4-Amido-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-ones as New Potent and Selective Human A3 Adenosine Receptor Antagonists. Synthesis, Pharmacological Evaluation and Ligand-Receptor Modeling Studies.

COLOTTA, VITTORIA;CATARZI, DANIELA;VARANO, FLAVIA;FILACCHIONI, GUIDO;
2006

Abstract

A structural investigation on some 4-amido-2-phenyl-1,2-dihydro-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives, designed as human A3 adenosine receptor (hA3 AR) antagonists, is described. In the new derivatives, some acyl residues with different steric bulk were introduced on the 4-amino group, and their combination with the 4-methoxy group on the 2-phenyl moiety, and/or the 6-nitro/6-amino substituent on the fused benzo ring, was also evaluated. Most of the new derivatives were potent and selective hA3 AR antagonists. SAR analysis showed that hindering and lipophilic acyl moieties not only are well tolerated but even ameliorate the hA3 affinity. Interestingly, the 4-methoxy substituent on the appended 2-phenyl moiety, as well as the 6-amino group, always exerted a positive effect, shifting the affinity toward the hA3 receptor subtype. In contrast, the 6-nitro substituent exerted a variable effect. An intensive molecular modeling investigation was performed to rationalize the experimental SAR findings.
2006
49
3916
3925
O. LENZI; V. COLOTTA; D. CATARZI; F.VARANO; G. FILACCHIONI; C. MARTINI; L. TRINCAVELLI; OSELE CIAMPI; KATIA VARANI; FEDERICO MARIGHETTI; ERIKA MORIZZO; STEFANO MORO
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/312840
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