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2004
Pyridine derivatives
R 0380
Synthesis of 1H-Pyridin-2-one Derivatives as Potent and Selective FarnesyltransInhibitors. — The A-ring replacement of a potent and selective FTase inhibitor
52- 123 ferase
with two new pyridone moieties gives rise to the synthesis of two series of novel FTase
inhibitors. Both series contain members having potent activity against FTase and excellent selectivity for FTase over GGTase-I. In addition to its potent whole-cell activity,
(VIa) reveals good oral bioavailability. Furthermore, novel heterocycles of type (XV)
are synthesized, which are the precursors of potent FTase inhibitors in the second series.
The structure of (XVa) is confirmed by X-ray crystallography. — (WANG*, L.; et al.;
Bioorg. Med. Chem. Lett. 14 (2004) 18, 4603-4606; Cancer Res., Abbott Lab., Abbott
Park, IL 60064, USA; Eng.) — H. Hoennerscheid
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