The synthesis, conformation and antimuscarinic properties of ketone analogues of tropane esters

TAVASLI M., O'Hagan D., Batsanov A., Foxon G., Halliwell R., Howard J.

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, no.23, pp.3455-3461, 1999 (SCI-Expanded) identifier identifier


A synthesis of the ketone analogues of three naturally occurring tropane esters has been developed and one of the ketones has been evaluated for its efficacy as a muscarinic acetylcholine receptor (mAChR) antagonist in guinea-pig ileum. The ketone analogue of apoatropine displayed an IC50 value in the micromolar range when compared to atropine, which has antagonist activity in the nanomolar range. The conformational change in replacing the bridging oxygen of the ester moiety by CH2 has been assessed by X-ray structure analysis of one of the compounds and has been evaluated more widely in a Cambridge Crystallographic Database survey. The structural data reveals that both the tropane esters and tropane ketones adopt similar conformations.