Studies on disease-modifying antirheumatic drugs. II. Synthesis and activity of the metabolites of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmethyl)quino line-3-carboxylate (TAK-603).
The metabolites of ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-ylmeth yl)quinoline -3-carboxylate (1, TAK-603), which is under clinical evaluation as a new type of disease-modifying antirheumatic drug (DMARD), were prepared to confirm their structures and to study their pharmacological properties. Of the metabolites identified, the 4-(4-hydroxy-3-methoxyphenyl) derivative (2c, M-I) was found to have an anti-inflammatory effect in an adjuvant arthritic rat model, although its potency in this model was slightly lower than that of the parent compound.
Baba
A
A
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Makino
H
H
Ohta
Y
Y
Sohda
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D001711:Biotransformation; D002455:Cell Division / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011804:Quinolines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D011804:Quinolines; D014230:Triazoles; C104411:TAK 603