1,2,5-Oxadiazole analogues of leflunomide and related compounds.
A new series of compounds, structurally related to leflunomide, based on the 1,2,5-oxadiazole ring system (furazan) has been synthesised, and their ability to undergo ring scission at physiological pH to afford the corresponding cyano-oximes has been analyzed. The latter, together with the respective nitro derivatives obtained by oxidation, have been characterised as weak inhibitors of rat dihydroorotate dehydrogenase (DHODH).
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via Pietro Giuria 9, I-10125 Torino, Italy.
Marta
M
Giorgis
Marco Lucio
ML
Lolli
Barbara
B
Rolando
Angela
A
Rao
Paolo
P
Tosco
Shilpi
S
Chaurasia
Domenica
D
Marabello
Roberta
R
Fruttero
Alberto
A
Gasco
D000818:Animals; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology; D000077339:Leflunomide; D008297:Male; D008958:Models, Molecular; D010069:Oxadiazoles / Q000737:chemistry*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors / Q000737:chemistry; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar
D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D010069:Oxadiazoles; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000077339:Leflunomide