The design of 8,8-dimethyl[1,6]naphthyridines as potential anticonvulsant agents.
Starting from a series of 7-linked tetrahydroisoquinoline derivatives, as exemplified by SB-270664, a new series of 8,8-dimethylnaphthyridine compounds has been identified. SAR studies around these attractive leads have provided compounds such as 12 which display excellent anticonvulsant activity and an encouraging pharmacokinetic profile in vivo.
Neurology & GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Research & Development Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
Nigel E
NE
Austin
Michael S
MS
Hadley
John D
JD
Harling
Frank P
FP
Harrington
Gregor J
GJ
Macdonald
Darren J
DJ
Mitchell
Graham J
GJ
Riley
Tania O
TO
Stean
Geoffrey
G
Stemp
Sharon C
SC
Stratton
Mervyn
M
Thompson
Neil
N
Upton
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines
D000927:Anticonvulsants; D009287:Naphthyridines; D044005:Tetrahydroisoquinolines