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 thieno2,3-b]pyridine and thieno2,3-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 Friedl?nder 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)thieno2,3-b:5,4-c'] dipyridine-3-carboxylate (21) exhibited more potent activity than TAK-603.