title: Highly potent inhibitors of TNF-alpha production. Part I: discovery of new chemical leads and their structure-activity relationships.
abstract: 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.
authors.affiliation: Fukui Research Institute, Ono Pharmaceutical Co., Ltd., Technoport, Yamagishi, Mikuni, Sakai, Fukui, Japan. to.matsui@ono.co.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nishita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itadani
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakatani
authors.forename: Nagashige
authors.initials: N
authors.lastname: Omawari
authors.forename: Masaru
authors.initials: M
authors.lastname: Sakai
authors.forename: Shuichi
authors.initials: S
authors.lastname: Nakazawa
authors.forename: Akihito
authors.initials: A
authors.lastname: Ogata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mori
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Terai
authors.forename: Wataru
authors.initials: W
authors.lastname: Kamoshima
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; 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
chemical_list: D007189:Indans; D008070:Lipopolysaccharides; D009943:Organophosphorus Compounds; D014409:Tumor Necrosis Factor-alpha