Synthesis of beta-spiro[pyrrolidinoindolines], their binding to the glycine receptor, and in vivo biological acitivity.
A series of beta-spiro[pyrrolidinoindolines], 3a-d, was prepared and evaluated for their ability to bind to the glycine receptor. These compounds were also tested in vivo to determine if they would produce convulsant or anxiolytic effects. The target indolines were chosen because they represent rings A, B, E, and a portion of ring C of strychnine. Results of this study indicate that, in this series, an acetylindoline in the endo configuration and a tertiary amine, such as that of the pyrrolidine ring nitrogen, are required for biological activity. In all of the cases studied, the activity was of a convulsant rather than a relaxant nature. Excellent correlation was found to exist between the binding affinities to the strychnine site of the glycine receptor and clonic convulsions (ED50) and death (LD50) in the mouse.
D000818:Animals; D003292:Convulsants / Q000138:chemical synthesis* / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013331:Strychnine / Q000378:metabolism
D003292:Convulsants; D007211:Indoles; D017981:Receptors, Neurotransmitter; D013331:Strychnine; D005998:Glycine