title: Syntheses and structure-activity relationships of novel, potent, and selective trans-2-[3-oxospiro[isobenzofuran-1(3H),1'-cyclohexan]-4'-yl]benzimidazole NPY Y5 receptor antagonists.
abstract: Syntheses and structure-activity relationships of a novel class of 2-[3-oxospiro[isobenzofuran-1(3H),1'-cyclohexan]-4'-yl]benzimidazole NPY Y5 receptor antagonists are described. Optimization of the lead compound 2a by incorporating substituents into the 5-position or into both the 5- and 6-positions of the benzimidazole core part led to the identification of 5-(5-methyl-1,2,4-oxadiazol-2-yl)benzimidazole (2r: IC(50)=3.3 nM) and 5-(2-methyltetrazol-5-yl)benzimidazole (2u: IC(50)=5.9 nM), both of which are potent, selective, and orally bioavailable Y5 receptor antagonists.
authors.affiliation: Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Okubo-3, Tsukuba 300-2611, Ibaraki, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ogino
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ohtake
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nagae
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuda
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Maki
authors.initials: M
authors.lastname: Kanesaka
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mitobe
authors.forename: Junko
authors.initials: J
authors.lastname: Ito
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kanno
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohe
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami