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.
Austin
Nigel E
NE
Neurology & GI Centre of Excellence for Drug Discovery, GlaxoSmithKline Research & Development Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
Hadley
Michael S
MS
Harling
John D
JD
Harrington
Frank P
FP
Macdonald
Gregor J
GJ
Mitchell
Darren J
DJ
Riley
Graham J
GJ
Stean
Tania O
TO
Stemp
Geoffrey
G
Stratton
Sharon C
SC
Thompson
Mervyn
M
Upton
Neil
N
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