Synthesis, structure-activity relationships, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3-hydroxy-N-[3'-methyl-4 …

…, N McDowall, CB Jones, CJR Hedgecock…

文献索引：Kuo, Elizabeth A.; Hambleton, Philip T.; Kay, David P.; Evans, Phillip L.; Matharu, Saroop S.; Little, Edward; McDowall, Neil; Jones, C. Beth; Hedgecock, Charles J. R.; Yea, Christopher M.; Chan, A. W. Edith; Hairsine, Peter W.; Ager, Ian R.; Tully, W. Roger; Williamson, Richard A.; Westwood, Robert Journal of Medicinal Chemistry, 1996 , vol. 39, # 23 p. 4608 - 4621

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被引用次数: 88

摘要

The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biological activity determined in rat and mouse delayed type hypersensitivity has been found to correlate well with their in ...