SAR, species specificity, and cellular activity of cyclopentene dicarboxylic acid amides as DHODH inhibitors.
Novel DHODH inhibitors were developed based on a previously described series by introduction of heteroatoms into the cyclopentene ring and hydroxyl groups attached to it. Also, the hydrophobic biphenyl side chain was replaced with benzyloxy phenyl groups. Activities on human, rat, and mouse enzymes indicate a species specificity of these inhibitors.
Leban
Johann
J
4SC AG, Am Klopferspitz 19a, 82152 Martinsried, Germany. leban@4sc.com
Kralik
Martin
M
Mies
Jan
J
Gassen
Michael
M
Tentschert
Karin
K
Baumgartner
Roland
R
D000577:Amides; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology; D004081:Dihydroorotate Oxidase / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D051379:Mice; D051381:Rats; D013045:Species Specificity; D013329:Structure-Activity Relationship
D000577:Amides; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; C409963:cyclopentenedicarboxylic acid; D004081:Dihydroorotate Oxidase