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2004
Thiadiazole derivatives
R 0300
Discovery of Thiadiazoles as a Novel Structural Class of Potent and Selective
Inhibitors. Part 2. Metabolism-Directed Optimization Studies Towards
51- 102 PDE7
Orally Bioavailable Derivatives. — A metabolism-directed optimization study leads
to appropriate modifications of the metabolically labile structural parts of previously
reported potent and selective PDE7 inhibitors to generate compounds with improved
pharmacokinetics. Hydroxylated cyclohexyl derivatives are prepared as potential metabolites of a representative PDE7 inhibitor. Derivatives (X) and (XII) illustrate a successful optimization approach enabling the design of compounds possessing improved
in vivo pharmacokinetics. — (VERGNE*, F.; et al.; Bioorg. Med. Chem. Lett. 14
(2004) 18, 4615-4621; Aventis Pharm., F-94400 Vitry-sur-Seine, Fr.; Eng.) —
H. Hoennerscheid
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