The design of 8,8-Dimethyl[1,6]naphthyridines as potential anticonvulsant agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 10; pp. 1627 - 1629
• Main Authors: Austin, Nigel E, Hadley, Michael S, Harling, John D, Harrington, Frank P, Macdonald, Gregor J, Mitchell, Darren J, Riley, Graham J, Stean, Tania O, Stemp, Geoffrey, Stratton, Sharon C, Thompson, Mervyn, Upton, Neil
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 19.05.2003; Elsevier
• Subjects: Administration, Oral; Animals; Anticonvulsants - chemical synthesis; Anticonvulsants - pharmacokinetics; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Design; Medical sciences; Naphthyridines - chemical synthesis; Naphthyridines - pharmacokinetics; Naphthyridines - pharmacology; Neuropharmacology; Pharmacology. Drug treatments; Rats; Seizures - drug therapy; Seizures - prevention & control; Structure-Activity Relationship; Tetrahydroisoquinolines; Ether; Rat; Nitrogen heterocycle; Rodentia; Benzene derivatives; Oral administration; Anticonvulsant; Bioavailability; In vitro; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Convulsion; Structure activity relation; Animal; Bicyclic compound; Carboxamide; Fluorine Organic compounds; Neurological disorder; Pharmacokinetics; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(03)00288-9

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. SAR studies on naphthyridines acting at the [ 3H] SB-204269 binding site have provided anticonvulsants (e.g., 12) with excellent pharmacokinetic parameters.