title: Identification of positron emission tomography ligands for NPY Y5 receptors in the brain.
abstract: A series of trans-3-oxospiro[(aza)isobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide derivatives were synthesized and profiled for NPY Y5 binding affinity, brain and CSF penetrability in rats, and susceptibility to human and mouse P-glycoprotein transporters in order to develop a PET ligand. Compound 12b exhibited an acceptable profile for a PET ligand, and [(11)C]12b was successfully utilized in clinical settings as a Y5 PET ligand.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba 300-2611, Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haga
authors.forename: Takunobu
authors.initials: T
authors.lastname: Shibata
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Nonoshita
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Moriya
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohe
authors.forename: Masato
authors.initials: M
authors.lastname: Chiba
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mitobe
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kitazawa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwaasa
authors.forename: Akane
authors.initials: A
authors.lastname: Ishihara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Akio
authors.initials: A
authors.lastname: Kanatani
authors.forename: Takehiro
authors.initials: T
authors.lastname: Fukami
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002460:Cell Line; D002555:Cerebrospinal Fluid / Q000000981:diagnostic imaging; D006801:Humans; D008024:Ligands; D051379:Mice; D010949:Plasma / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011869:Radioligand Assay / Q000379:methods*; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008024:Ligands; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor