Totleben MJ

References (1)

Title : Syntheses of benzoquinolizidine and benzoindolizidine derivatives as anti-amnesic agents - Zhao_1999_Bioorg.Med.Chem_7_1637
Author(s) : Zhao S , Totleben MJ , Freeman JP , Bacon CL , Fox GB , O'Driscoll E , Foley AG , Kelly J , Farrell U , Regan C , Mizsak SA , Szmuszkovicz J
Ref : Bioorganic & Medicinal Chemistry , 7 :1637 , 1999
Abstract : Tacrine, one of the drugs available for Alzheimer's disease based on the cholinergic approach, suffers from considerable toxicity. Many analogues of tacrine have been prepared which retain the pharmacologically rich aminopyridine or aminoquinoline motifs. The current research was undertaken to produce an acetylcholinesterase inhibitor by employing 11-aminobenzoquinolizidines (4) and 10-aminobenzoindolizidines (5) as templates. Thus, we aimed to achieve three goals relative to tacrine: eliminate the pyridine and quinoline moieties and render the molecule less flat. Overall, the compounds we prepared were poorer inhibitors of acetylcholinesterase compared to tacrine. The single exception was compound 6f which exhibited an effect comparable to that of tacrine, but only at a dose of the order of 10(-3) M. However, despite the poor acetylcholinesterase inhibition by 6b, this compound proved to be an effective anti-amnesic agent at 45 mg/kg dose.
ESTHER : Zhao_1999_Bioorg.Med.Chem_7_1637
PubMedSearch : Zhao_1999_Bioorg.Med.Chem_7_1637
PubMedID: 10482456