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Leflunomide's Bioactive Metabolite Has the Minimal Structural Requirements for the Efficient Inhibition of Human Dihydroorotate Dehydrogenase

✍ Scribed by Christos Papageorgiou; M. Zurini; Hans-Peter Weber; Xaver Borer


Publisher
Elsevier Science
Year
1997
Tongue
English
Weight
192 KB
Volume
25
Category
Article
ISSN
0045-2068

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✦ Synopsis


The Ͱ-cyano-ͱ-hydroxy enamide 1 is an inhibitor of human dihydroorotate dehydrogenase (IC 50 ϭ 0.26 ȐM), the rate-limiting enzyme in the de novo pyrimidine biosynthesis. A structure-activity analysis based on selected derivatives of 1 demonstrates that both its structural characteristics and its physicochemical properties are mandatory for the efficient inhibition of the enzyme.