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.
Roche Bioscience, 3401 Hillview Avenue, Palo Alto, CA 94304, USA. jianc@amgen.com
Jian Jeffrey
JJ
Chen
Nolan
N
Dewdney
Xiaohong
X
Lin
Robert L
RL
Martin
Keith A M
KA
Walker
Jane
J
Huang
Frances
F
Chu
Elsie
E
Eugui
Anna
A
Mirkovich
Yong
Y
Kim
Keshab
K
Sarma
Humberto
H
Arzeno
Harold E
HE
Van Wart
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