title: Design, synthesis and structure-activity relationships of novel benzoxazolone derivatives as 18 kDa translocator protein (TSPO) ligands.
abstract: Selective 18 kDa translocator protein (TSPO) ligands are expected to be therapeutic agents with a wide spectrum of action on psychiatric disorders and fewer side effects. We designed novel benzoxazolone derivatives and examined the structure-activity relationship (SAR) of a series of compounds with various substituents at the amide part and C-5 position. Although a number of the synthesized compounds showed high TSPO binding affinity, these compounds had poor drug-like properties. Further optimization of pharmacokinetic properties of these compounds led to discovery of compound 74, which exhibited anxiolytic effect in the rat Vogel conflict model.
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan. takayuki-fukaya@ds-pharma.co.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukaya
authors.forename: Toru
authors.initials: T
authors.lastname: Kodo
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishiyama
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Kakuyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Satoko
authors.initials: S
authors.lastname: Baba
authors.forename: Shuji
authors.initials: S
authors.lastname: Masumoto
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001583:Benzoxazoles; D002352:Carrier Proteins; D008024:Ligands; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; C017057:benzoxazolone