Synthesis of beta-hydroxy-propenamide derivatives and the inhibition of human dihydroorotate dehydrogenase.
Novel beta-hydroxy propenamides as analogues of the active metabolite of leflunomide (A 771726) were synthesized and evaluated for their inhibitory activity on dihydroorotate dehydrogenase (DHODH) in an investigation into their immunosuppressive activity. Compounds 2a, 3a, and 3h were approximately 4-40 times more potent than leflunomide in their activity while they were-less active than A 771726.
Kim
Taek Hyeon
TH
Department of Applied Chemistry, College of Engineering, Chonnam National University, Gwangju 500-757, Korea. thkim@chonnam.ac.kr
Na
Hye-Sun
HS
Löffler
Monika
M
D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003437:Crotonates; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006885:Hydroxybutyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007555:Isoxazoles / Q000378:metabolism; D000077339:Leflunomide; D009570:Nitriles; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014052:Toluidines
D000814:Aniline Compounds; D003437:Crotonates; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D006885:Hydroxybutyrates; D007555:Isoxazoles; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000077339:Leflunomide