Synthesis and preliminary biological evaluation of new alpha-amino amide anticonvulsants incorporating a dextromethorphan moiety.
Dextromethorphan 1 is an effective neuroprotectant in animal models of epilepsy and ischemia but showed side-effects during clinical trials limiting its potential use in a clinical setting. Here we describe the enantioselective and enantiospecific syntheses and the initial in vitro and in vivo biological evaluation of new hybrid structures between 1 and a previously disclosed alpha-amino amide anticonvulsant (3).
Pevarello
P
P
Pharmacia & Upjohn, Chem. Dept., Nerviano, Milan, Italy. paolo.pevarello@eu.pnu.com
Traquandi
G
G
Bonsignori
A
A
McArthur
R A
RA
Maj
R
R
Caccia
C
C
Salvati
P
P
Varasi
M
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001596:Benzylamines / Q000138:chemical synthesis* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D003915:Dextromethorphan / Q000031:analogs & derivatives / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D051381:Rats
D000927:Anticonvulsants; D001596:Benzylamines; D003915:Dextromethorphan; C092797:safinamide; D000409:Alanine