Inhibitors of dihydroorotate dehydrogenase

Dihydroorotate dehydrogenase (DHODase) is the rate-limiting step in de novo pyrimidine biosynthesis, required for the proliferation of many cell types and for the growth of microorganisms. Inhibitors of this enzyme have poten tial as immunosuppressive agents for the prevention of organ transplant rej ection, and for the treatment of autoimmune diseases such as rheumatoid art hritis (RA). Other possible applications are as anti-infective agents such as antimalarials and antibacterials. Two major chemical classes of mammalia n DHODase inhibitors have been described in the literature, based on the dr ugs brequinar (BQR) and leflunomide (LFM). A few inhibitors of microbial en zymes have also been disclosed. Since DHODase inhibition has not yet been r eviewed, this paper covers the patents and associated publications which ha ve appeared during the past 13 years.