Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4'-piperidin]-1'-yl}benzimidazole derivatives.
Design, syntheses, and structure-activity relationships of a novel class of 2-{3-oxospiro[isobenzofuran-1(3H),4'-piperidin]-1'-yl}benzimidazole NPY Y5 receptor antagonists are described. The benzimidazole structures were newly designed based on the urea linkage of our prototype Y5 receptor antagonists (2 and 3). By optimizing substituents on the benzimidazole core part of the lead compound 5a, we were able to develop a potent, orally available, and brain-penetrable Y5 selective antagonist (5k).
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
Moriya
Minoru
M
Suga
Takuya
T
Ishikawa
Makoto
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
D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D015394:Molecular Structure; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor