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.
D000478:Alkylation; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D011187:Posture; D011759:Pyrrolidines; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology
D007211:Indoles; D011759:Pyrrolidines; D013141:Spiro Compounds; C049802:6-(3-indolylmethyl)-7-methyl-1,4-dioxa-7-azaspiro(4,5)-decane; C049803:6-benzyl-7-methyl-1,4-dioxa-7-azaspiro(4,5)decane; C049801:6-(4-indolylmethyl)-7-methyl-1,4-dioxa-7-azaspiro(4,5)decane; D013134:Spiperone; D001058:Apomorphine; D004298:Dopamine