Discovery of novel phosphonic acid derivatives as new chemical leads for inhibitors of TNF-alpha production.
2-(Acylamino)benzylphosphonic acid 6 derived from an artificial substrate of sphingomyelinase was found to show inhibitory activity of TNF-alpha production. Structural optimization was started with the chemical modification of 6. The discovery of another chemical leads 7, 8, 10 and 16 for the development of structurally new inhibitors of TNF-alpha production is reported.
Matsui
Toshiaki
T
Fukui Research Institute, Ono Pharmaceutical Co., Ltd., Yamagishi, Mikuni, Sakai, Fukui, Japan. to.matsui@ono.co.jp
Takahashi
Shinya
S
Matsunaga
Naoki
N
Nakamura
Kazunori
K
Omawari
Nagashige
N
Sakai
Masaru
M
Kamoshima
Wataru
W
Terai
Kouichiro
K
Ohno
Hiroyuki
H
Obata
Takaaki
T
Nakai
Hisao
H
Toda
Masaaki
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D007189:Indans; D008070:Lipopolysaccharides; D010721:Phosphinic Acids; D014409:Tumor Necrosis Factor-alpha