Structure-activity relationships of some Galbulimima alkaloids related to himbacine

Himbacine, himbeline, N-methylhimandravine and himandravine together with their dihydro-derivatives were evaluated as antagonists of muscarinic receptors in guinea-pig ileal longitudinal muscle and electrically stimulated left atrium. Himbacine was the most potent compound and the 15-fold selectivity exhibited for the M2 muscarinic receptor was greater than that found with any of the other compounds examined. Reduction of the double bond linking the decalin ring system and the piperidine ring almost abolished selectivity in dihydrohimbacine. Removal of the N-methyl group in himbacine to form himbeline was associated with reduced selectivity. However the corresponding change in converting N-methylhimandravine to himandravine was not associated with any change in selectivity suggesting that orientation of the 2-methyl group in the piperidine ring may be important for selectivity.