An improved synthesis of the enantiomers of BM-5 and their effects on the central in vivo release of acetylcholine.
Racemic N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5), a putative postsynaptic agonist and presynaptic antagonist at muscarinic receptors, was resolved into the enantiomers by a new method suitable for large scale preparation. The method involves a chemoselective N-debenzylation as the key step. The enantiomers of BM-5 were obtained after six separate steps in 25% overall yield. The ability of the enantiomers to release acetylcholine was evaluated in vivo by use of brain dialysis. (R)-BM-5 was the more potent enantiomer in this assay.
Nilsson
B M
BM
Department of Organic Pharmaceutical Chemistry, Uppsala University, Sweden.
De Boer
P
P
Grol
C J
CJ
Hacksell
U
U
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002852:Chromatography, Ion Exchange; D003956:Dialysis; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010277:Parasympathomimetics / Q000138:chemical synthesis* / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects
D010277:Parasympathomimetics; D011759:Pyrrolidines; D011976:Receptors, Muscarinic; C038672:N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide; D000109:Acetylcholine