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.
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.
Ogino
Yoshio
Y
Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Okubo-3, Tsukuba 300-2611, Ibaraki, Japan.
Ohtake
Norikazu
N
Nagae
Yoshikazu
Y
Matsuda
Kenji
K
Ishikawa
Makoto
M
Moriya
Minoru
M
Kanesaka
Maki
M
Mitobe
Yuko
Y
Ito
Junko
J
Kanno
Tetsuya
T
Ishihara
Akane
A
Iwaasa
Hisashi
H
Ohe
Tomoyuki
T
Kanatani
Akio
A
Fukami
Takehiro
T