Synthesis and biological evaluation of bicyclic and tricyclic substituted nortropane derivatives: discovery of a novel selective alpha1D-adrenergic receptor ligand.

A range of 3,6,6-trisubstituted nortropane derivatives based upon 6beta-phenyltropane-3beta,6 alpha-diol have been synthesised from 6beta-hydroxytropinone, including some novel related tricyclic hemi-ketal and tricyclic ketal compounds. Derivatives were assessed for pharmacological affinity and selectivity at alpha(1)-adrenergic receptors, and 6beta-phenyl-8-azabicyclo[3.2.1]octan-3-spiro-2'-(1',3'-dioxolane)-6-ol, a novel lead compound selective for the alpha(1D)-adrenergic receptor, is reported.