Triquinane-based compounds as possible serotonin 5-HT(6) receptor antagonists for the treatment of Alzheimer's disease.
The recently discovered serotonin 5-HT(6) receptor is a novel target for the treatment of cognitive decline associated with neurodegenerative diseases such as Alzheimer's disease (AD). Several studies have shown that antagonism of this receptor leads to improved learning and memory. Two serotonin 5-HT(6) receptor antagonists are currently in Phase II clinical trials for cognitive enhancement. Striking structural similarities between the polycyclic features of some 5-HT(6) antagonists and those of the cis-syn-cis triquinane ring system led us to propose that triquinane-derived compounds may represent a novel class of 5-HT(6) receptor antagonists. Using computational methodologies, we propose a structure with features that may impart potent 5-HT(6) receptor antagonistic activities to the triquinane ring complex. Related compounds, once synthesized, may have possible utility in the treatment of cognitive decline associated with AD.
Geldenhuys
Werner J
WJ
Texas Tech University Health Sciences Center, School of Pharmacy, 1300 Coulter Drive, Amarillo, TX 79106, USA.
Van der Schyf
Cornelis J
CJ
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D001665:Binding Sites; D001812:Blood-Brain Barrier / Q000378:metabolism; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods; D015195:Drug Design; D005240:Feasibility Studies; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C097216:serotonin 6 receptor