Discovery of substituted 2,4,4-triarylimidazoline derivatives as potent and selective neuropeptide Y Y5 receptor antagonists.
Novel imidazoline derivatives were discovered to be potent neuropeptide Y Y5 receptor antagonists. High-throughput screening of Merck sample collections against the human Y5 receptor resulted in the identification of 2,4,4-triphenylimidazoline (1), which had an IC(50) of 54nM. Subsequent optimization led to the identification of several potent derivatives.
Sato
Nagaaki
N
Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Company, Ltd, 3 Okubo, Tsukuba 300-2611, Japan.
Jitsuoka
Makoto
M
Ishikawa
Shiho
S
Nagai
Keita
K
Tsuge
Hiroyasu
H
Ando
Makoto
M
Okamoto
Osamu
O
Iwaasa
Hisashi
H
Gomori
Akira
A
Ishihara
Akane
A
Kanatani
Akio
A
Fukami
Takehiro
T
D000818:Animals; D001921:Brain / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D017476:Receptors, Neuropeptide Y / Q000737:chemistry*; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D007093:Imidazoles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor