Biphenyl-4-ylcarbamoyl thiophene carboxylic acids as potent DHODH inhibitors.
A previously discovered DHODH inhibitor series was further improved by replacing the cyclopentene ring by aromatic heterocycles. Different isomers of these compounds were prepared by the directed ortho-metallation procedure. The compounds are more active than the corresponding cyclopentene analogs and show potent effects on PBMC's proliferation.
Leban
Johann
J
4SC AG, Am Klopferspitz 19a, 82152 Martinsried, Germany. leban@4sc.com
Kralik
Martin
M
Mies
Jan
J
Baumgartner
Roland
R
Gassen
Michael
M
Tasler
Stefan
S
D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000090722:Dihydroorotate Dehydrogenase; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D001713:Biphenyl Compounds; D002219:Carbamates; D002264:Carboxylic Acids; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D013876:Thiophenes; D044925:Oxidoreductases Acting on CH-CH Group Donors