title: Highly potent inhibitors of TNF-alpha production. Part II: metabolic stabilization of a newly found chemical lead and conformational analysis of an active diastereoisomer.
abstract: Design and synthesis of metabolically stabilized inhibitors of TNF-alpha production, which could be new drug candidates, are reported. Conformational analysis of an active diastereoisomer was performed based on biological evaluations of the conformationally fixed indane derivatives 17 and 18. Structure-activity relationships (SARs) based on biological evaluations of the optically active derivatives are also discussed. Full details including chemistry are reported.
authors.affiliation: Fukui Research Institute, Ono Pharmaceutical Co., Ltd., Technoport, Yamagishi, Mikuni, Sakai, 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: Hiroshi
authors.initials: H
authors.lastname: Tsuruta
authors.forename: Setsuko
authors.initials: S
authors.lastname: Fujita
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: 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; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy; D004355:Drug Stability; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D020714:Maximum Tolerated Dose; D051379:Mice; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015996:Survival Rate; D014018:Tissue Distribution; 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