Highly potent inhibitors of TNF-alpha production. Part I: discovery of new chemical leads and their structure-activity relationships.
Discovery of new chemical leads of inhibitors for TNF-alpha production starting from the chemical modification of 1 is reported. Further biological studies of 1 to disclose the site of its action strongly suggested that 1 inhibits LPS-induced TNF-alpha expression in the liver and spleen of mice. Structure-activity relationships (SARs) are also discussed and full details including the chemistry are reported.
Matsui
Toshiaki
T
Fukui Research Institute, Ono Pharmaceutical Co., Ltd., Technoport, Yamagishi, Mikuni, Sakai, Fukui, Japan. to.matsui@ono.co.jp
Kondo
Takashi
T
Nishita
Yoshitaka
Y
Itadani
Satoshi
S
Nakatani
Shingo
S
Omawari
Nagashige
N
Sakai
Masaru
M
Nakazawa
Shuichi
S
Ogata
Akihito
A
Mori
Hideaki
H
Terai
Kouichiro
K
Kamoshima
Wataru
W
Ohno
Hiroyuki
H
Obata
Takaaki
T
Nakai
Hisao
H
Toda
Masaaki
M
D000818:Animals; D005260:Female; D007189:Indans / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D013154:Spleen / Q000737:chemistry; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D007189:Indans; D008070:Lipopolysaccharides; D009943:Organophosphorus Compounds; D014409:Tumor Necrosis Factor-alpha