Synthesis and pharmacological evaluation of some 6-substituted 7-methyl-1,4-dioxa-7-azaspiro[4.5]decanes as potential dopamine agonists.

Three 7-methyl-1,4-dioxa-7-azaspiro[4.5]decanes that contained either the benzyl, 3-indolylmethyl, or 4-indolylmethyl group at the 6-position were synthesized via alkylation of the pyrrolidine enamine of the key intermediate, ethyl 3-oxopiperidine-1-carboxylate. The spirodecane derivatives were evaluated for in vivo central and peripheral dopamine agonist activity. None of the compounds displayed central nervous system activity; however, the 4-indolymethyl analogue exhibited potent dopamine agonist activity in the cat cardioaccelerator nerve assay and possesses an ID50 of 0.095 mumol/kg compared to apomorphine, which possesses an ID50 of 0.0348 mumol/kg in the same assay.