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Human dihydroorotate dehydrogenase(hsDHODH),a flavin-dependent mitochondrial enzyme,plays a rate-limiting role in pyrimidine de novo biosynthesis,which has been identified as a potential target for the treatment of autoimmune diseases such as rheumatoid arthritis.[1] On the basis of lead hit 413,a series of novel thiazole-scaffold derivatives were designed and synthesized.