Design and synthesis of orally active inhibitors of TNF synthesis as anti-rheumatoid arthritis drugs.
A novel series of TNF inhibitors was identified based on the screening of existing MMP inhibitor libraries. Further SAR optimization led to the discovery of a novel lead compound. Its synthesis, efficacy in experimental animal models, and pharmacokinetic data are discussed.
Chen
Jian Jeffrey
JJ
Roche Bioscience, 3401 Hillview Avenue, Palo Alto, CA 94304, USA. jianc@amgen.com
Dewdney
Nolan
N
Lin
Xiaohong
X
Martin
Robert L
RL
Walker
Keith A M
KA
Huang
Jane
J
Chu
Frances
F
Eugui
Elsie
E
Mirkovich
Anna
A
Kim
Yong
Y
Sarma
Keshab
K
Arzeno
Humberto
H
Van Wart
Harold E
HE
D000818:Animals; D018501:Antirheumatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha