2003 Fused pyridine derivatives

Fused pyridine derivativesR 0450 The Design of 8,8-Dimethyl[1,6]naphthyridines as Potential Anticonvulsant

Agents. — Design and structure—activity relationship analysis provides a series of naphthyridines for further exploration. In this series, the gem dimethyl group is intro-duced to prevent aromatization, and the fused phenyl ring of the key lead compound is replaced by a pyridyl ring to reduce hydroxylation. The unpredictable and toxic dem-ethylation step [(III)→(IV)] requires an alternative pathway to the title compounds. The alternative route, cf. (V)→(IV), yields the targets (IV) in high overall yield (20%) com-pared to the published route (<4%). Naphthyridines like (IVc) display excellent anti-convulsant activity and an encouraging pharmacokinetic profile in vivo. — (THOMPSON*, M.; et al.; Bioorg. Med. Chem. Lett. 13 (2003) 10, 1627-1629; Dep. Discovery Chem., SmithKline Beecham Pharm., New Front. Sci. Park, Harlow, Essex CM19 5AW, UK; Eng.) — H. Hoennerscheid

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