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.
Institute for Biomolecular Science and Department of Chemistry, University of Wollongong, Northfields Ave, Wollongong, NSW 2522, Australia. susanmc@uow.edu.au
Susan J
SJ
McGinty
Angela
A
Finch
Renate
R
Griffith
Robert M
RM
Graham
John B
JB
Bremner
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008024:Ligands; D009662:Nortropanes / Q000138:chemical synthesis* / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D008024:Ligands; D009662:Nortropanes; D018340:Receptors, Adrenergic, alpha-1