Identification of positron emission tomography ligands for NPY Y5 receptors in the brain.
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.
Takahashi
Hirobumi
H
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba 300-2611, Japan.
Haga
Yuji
Y
Shibata
Takunobu
T
Nonoshita
Katsumasa
K
Sakamoto
Toshihiro
T
Moriya
Minoru
M
Ohe
Tomoyuki
T
Chiba
Masato
M
Mitobe
Yuko
Y
Kitazawa
Hidefumi
H
Iwaasa
Hisashi
H
Ishihara
Akane
A
Ishii
Yasuyuki
Y
Kanatani
Akio
A
Fukami
Takehiro
T
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008024:Ligands; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor