title: Discovery of novel phosphonic acid derivatives as new chemical leads for inhibitors of TNF-alpha production.
abstract: 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.
authors.affiliation: Fukui Research Institute, Ono Pharmaceutical Co., Ltd., Yamagishi, Mikuni, Sakai, Fukui, Japan. to.matsui@ono.co.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Shinya
authors.initials: S
authors.lastname: Takahashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsunaga
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakamura
authors.forename: Nagashige
authors.initials: N
authors.lastname: Omawari
authors.forename: Masaru
authors.initials: M
authors.lastname: Sakai
authors.forename: Wataru
authors.initials: W
authors.lastname: Kamoshima
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Terai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohno
authors.forename: Takaaki
authors.initials: T
authors.lastname: Obata
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: 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
chemical_list: D007189:Indans; D008070:Lipopolysaccharides; D010721:Phosphinic Acids; D014409:Tumor Necrosis Factor-alpha