Alpha1-adrenoceptor selective antagonists are crucial in investigating the role and biological functions of alpha1-adrenoceptor subtypes. We synthesized and studied the a1-adrenoceptor blocking properties of new molecules structurally related to the alpha1B-adrenoceptor selective antagonist (+)-cyclazosin, in an attempt to improve its receptor selectivity. In particular, we investigated the importance of substituents introduced at position 5 of the 2-furan moiety of (+)-cyclazosin and its replacement with classical isosteric rings. The 5-methylfuryl derivative (+)-3, [(+)-metcyclazosin], improved the pharmacological properties of the progenitor, displaying a competitive antagonism and an 11 fold increased selectivity for alpha1B over alpha1A, while maintaining a similar selectivity for the alpha1B-adrenoceptor relative to the alpha1D adrenoceptor. Compound (+)-3 may represent a useful tool for alpha1B adrenoceptor characterization in functional studies.

Synthesis and alpha1-adrenoceptor antagonist activity of derivatives and isosters of the furan portion of (+)-cyclazosin

SAGRATINI, Gianni;ANGELI, Piero;BUCCIONI, Michela;GULINI, Ugo;MARUCCI, Gabriella;GIARDINA', Dario
2007-01-01

Abstract

Alpha1-adrenoceptor selective antagonists are crucial in investigating the role and biological functions of alpha1-adrenoceptor subtypes. We synthesized and studied the a1-adrenoceptor blocking properties of new molecules structurally related to the alpha1B-adrenoceptor selective antagonist (+)-cyclazosin, in an attempt to improve its receptor selectivity. In particular, we investigated the importance of substituents introduced at position 5 of the 2-furan moiety of (+)-cyclazosin and its replacement with classical isosteric rings. The 5-methylfuryl derivative (+)-3, [(+)-metcyclazosin], improved the pharmacological properties of the progenitor, displaying a competitive antagonism and an 11 fold increased selectivity for alpha1B over alpha1A, while maintaining a similar selectivity for the alpha1B-adrenoceptor relative to the alpha1D adrenoceptor. Compound (+)-3 may represent a useful tool for alpha1B adrenoceptor characterization in functional studies.
2007
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/11581/201805
 Attenzione

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

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 13
social impact