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.
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
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Baba
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Makino
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Ohta
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Sohda
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