title: Discovery of substituted 2,4,4-triarylimidazoline derivatives as potent and selective neuropeptide Y Y5 receptor antagonists.
abstract: 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.
authors.affiliation: Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Company, Ltd, 3 Okubo, Tsukuba 300-2611, Japan.
authors.forename: Nagaaki
authors.initials: N
authors.lastname: Sato
authors.forename: Makoto
authors.initials: M
authors.lastname: Jitsuoka
authors.forename: Shiho
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Keita
authors.initials: K
authors.lastname: Nagai
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Tsuge
authors.forename: Makoto
authors.initials: M
authors.lastname: Ando
authors.forename: Osamu
authors.initials: O
authors.lastname: Okamoto
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Akira
authors.initials: A
authors.lastname: Gomori
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
mesh_terms: 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
chemical_list: D002264:Carboxylic Acids; D007093:Imidazoles; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor