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ID: ALA1147165
Journal: Bioorg Med Chem
Title: Synthesis and alpha(1)-adrenoceptor antagonist activity of derivatives and isosters of the furan portion of (+)-cyclazosin.
Authors: Sagratini G, Angeli P, Buccioni M, Gulini U, Marucci G, Melchiorre C, Leonardi A, Poggesi E, Giardinà D.
Abstract: alpha(1)-Adrenoceptor selective antagonists are crucial in investigating the role and biological functions of alpha(1)-adrenoceptor subtypes. We synthesized and studied the alpha(1)-adrenoceptor blocking properties of new molecules structurally related to the alpha(1B)-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 alpha(1B) over alpha(1A), while maintaining a similar selectivity for the alpha(1B)-adrenoceptor relative to the alpha(1D)-adrenoceptor. Compound (+)-3 may represent a useful tool for alpha(1B)-adrenoceptor characterization in functional studies.
CiteXplore: 17276073