Novel DMARDs on the basis of a new concept of dual cytokine regulation, TNF-alpha suppression and IL-10 augmentation.
A series of arylpiperazine derivatives was synthesized to obtain agents showing apparent therapeutic effects in a chronic inflammatory animal model, starting from a lead possessing potent dual cytokine regulatory activity in vivo. We found a pyrimidylpiperazine derivative 17c showing the dual regulatory activity and an excellent therapeutic effect in an adjuvant-induced arthritis model.
Hanano
T
T
Drug Discovery Laboratories, Pharmaceutical Research Division, Yoshitomi Pharmaceutical Industries, Ltd., Saitama, Japan. hanano@welfide.co.jp
Adachi
K
K
Aoki
Y
Y
Morimoto
H
H
Naka
Y
Y
Hisadome
M
M
Fukuda
T
T
Sumichika
H
H
D000818:Animals; D018501:Antirheumatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005528:Foot / Q000473:pathology; D005620:Freund's Adjuvant; D016753:Interleukin-10 / Q000819:agonists*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D018121:Receptors, Cytokine / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D008070:Lipopolysaccharides; D010879:Piperazines; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005620:Freund's Adjuvant