Synthesis and Structure−Activity Relationship of Fluoro Analogues of
8-{2-[4-(4-Methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as
Selective α1d-Adrenergic Receptor Antagonists

Konkel, Michael J.; Wetzel, John M.; Cahir, Marie; Craig, Douglas A.; Noble, Stewart A.; Gluchowski, Charles

doi:10.1021/jm0491391.s001

jm0491391_si_001.pdf (47.36 kB)

Synthesis and Structure−Activity Relationship of Fluoro Analogues of 8-{2-[4-(4-Methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as Selective α_1d-Adrenergic Receptor Antagonists

journal contribution

posted on 2005-04-21, 00:00 authored by Michael J. Konkel, John M. Wetzel, Marie Cahir, Douglas A. Craig, Stewart A. Noble, Charles Gluchowski

We have discovered high-affinity antagonists (exemplified by 11 and 12) that are the most selective for α_1d-adrenergic receptors (α_1d-AR) reported to date. In cloned receptor assay systems, 12 displays at least 95-fold selectivity for the α_1d-AR over all other G-protein-coupled receptors tested, and the subtype selectivity of 11 was confirmed in pharmacologically defined isolated tissue preparations.