The prazosin-related compd. (+)-cyclazosin [(+)-1 (I; R = H)] is an α1-adrenoceptor antagonist with moderate selectivity for the α1b-adrenoceptor subtype (selectivity ratio: α1b/α1a = 90, α1b/α1d = 24). To improve its pharmacol. profile, the novel chiral derivs. (+)-2-(+)-5, bearing a bromo, a Me, a methoxy or an acetyl group in position 5 of the 2-furoyl moiety, were synthesized and evaluated for their α1-adrenoceptor blocking activity. All the compds. displayed, like (+)-1, high and preferential affinity for the α1b-adrenoceptor in binding and functional assays. Interestingly, in functional assays, compds. (+)-3 (I; R = ME) and (+)-4 (I; R = OMe) showed, in comparison with (+)-1, an increase in the α1B/α1A selectivity (407 and 724 vs. 44), whereas compd. (+)-5 exhibited an improved α1B/α1D selectivity (1513 vs. 138).
(+)-Cyclazosin derivatives as α1-adrenoceptor antagonists
SAGRATINI, Gianni;BUCCIONI, Michela;MARUCCI, Gabriella;
2004-01-01
Abstract
The prazosin-related compd. (+)-cyclazosin [(+)-1 (I; R = H)] is an α1-adrenoceptor antagonist with moderate selectivity for the α1b-adrenoceptor subtype (selectivity ratio: α1b/α1a = 90, α1b/α1d = 24). To improve its pharmacol. profile, the novel chiral derivs. (+)-2-(+)-5, bearing a bromo, a Me, a methoxy or an acetyl group in position 5 of the 2-furoyl moiety, were synthesized and evaluated for their α1-adrenoceptor blocking activity. All the compds. displayed, like (+)-1, high and preferential affinity for the α1b-adrenoceptor in binding and functional assays. Interestingly, in functional assays, compds. (+)-3 (I; R = ME) and (+)-4 (I; R = OMe) showed, in comparison with (+)-1, an increase in the α1B/α1A selectivity (407 and 724 vs. 44), whereas compd. (+)-5 exhibited an improved α1B/α1D selectivity (1513 vs. 138).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
