Identification of positron emission tomography ligands for NPY Y5 receptors in the brain

Hirobumi Takahashi; Yuji Haga; Takunobu Shibata; Katsumasa Nonoshita; Toshihiro Sakamoto; Minoru Moriya; Tomoyuki Ohe; Masato Chiba; Yuko Mitobe; Hidefumi Kitazawa; Hisashi Iwaasa; Akane Ishihara; Yasuyuki Ishii; Akio Kanatani; Takehiro Fukami

doi:10.1016/j.bmcl.2009.07.103

Identification of positron emission tomography ligands for NPY Y5 receptors in the brain

Bioorg Med Chem Lett. 2009 Sep 15;19(18):5436-9. doi: 10.1016/j.bmcl.2009.07.103. Epub 2009 Jul 25.

Authors

Hirobumi Takahashi¹, Yuji Haga, Takunobu Shibata, Katsumasa Nonoshita, Toshihiro Sakamoto, Minoru Moriya, Tomoyuki Ohe, Masato Chiba, Yuko Mitobe, Hidefumi Kitazawa, Hisashi Iwaasa, Akane Ishihara, Yasuyuki Ishii, Akio Kanatani, Takehiro Fukami

Affiliation

¹ Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo 3, Tsukuba 300-2611, Japan.

PMID: 19679469
DOI: 10.1016/j.bmcl.2009.07.103

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.

Publication types

Evaluation Study

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Animals
Brain / diagnostic imaging*
Brain / metabolism
Cell Line
Cerebrospinal Fluid / diagnostic imaging
Humans
Ligands
Mice
Plasma / diagnostic imaging
Positron-Emission Tomography / methods*
Protein Binding
Radioligand Assay / methods*
Rats
Receptors, Neuropeptide Y / metabolism*
Structure-Activity Relationship

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Ligands
Receptors, Neuropeptide Y
neuropeptide Y5 receptor