Studies on disease-modifying antirheumatic drugs. IV. Synthesis of novel thieno[2,3-b:5,4-c']dipyridine derivatives and their anti-inflammatory effect.
The syntheses and anti-inflammatory activities of novel thieno[2,3-b]pyridine and thieno[2,3-b:5,4-c']-dipyridine derivatives are described. These compounds were designed by modification of the quinoline template of a new type of disease-modifying antirheumatic drug (DMARD), TAK-603, and prepared by the Friedländer reaction as a key reaction. Their anti-inflammatory effects were evaluated using an adjuvant arthritis rat model. Most of the compounds which included a diethylamino moiety in the side chain had potent anti-inflammatory effect. In particular, ethyl 2-(diethylaminomethyl)-4-(3,4-dimethoxyphenyl)thieno[2,3-b:5,4-c'] dipyridine-3-carboxylate (21) exhibited more potent activity than TAK-603.
Baba
A
A
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Mori
A
A
Yasuma
T
T
Unno
S
S
Makino
H
H
Sohda
T
T
D000818:Animals; D018501:Antirheumatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D005528:Foot / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology
D018501:Antirheumatic Agents; D011725:Pyridines; D011804:Quinolines; D014230:Triazoles; C104411:TAK 603