Synthesis and evaluation of a series of 2,4-diaminopyridine derivatives as potential positron emission tomography tracers for neuropeptide Y Y1 receptors

Minoru Kameda; Makoto Ando; Chisato Nakama; Kensuke Kobayashi; Hiroshi Kawamoto; Sayaka Ito; Tomoki Suzuki; Takeshi Tani; Satoshi Ozaki; Shigeru Tokita; Nagaaki Sato

doi:10.1016/j.bmcl.2009.07.030

Synthesis and evaluation of a series of 2,4-diaminopyridine derivatives as potential positron emission tomography tracers for neuropeptide Y Y1 receptors

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5124-7. doi: 10.1016/j.bmcl.2009.07.030. Epub 2009 Jul 10.

Authors

Minoru Kameda¹, Makoto Ando, Chisato Nakama, Kensuke Kobayashi, Hiroshi Kawamoto, Sayaka Ito, Tomoki Suzuki, Takeshi Tani, Satoshi Ozaki, Shigeru Tokita, Nagaaki Sato

Affiliation

¹ Department of Medicinal Chemistry, Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Co. Ltd, Okubo 3, Tsukuba, Ibaraki, Japan.

PMID: 19640706
DOI: 10.1016/j.bmcl.2009.07.030

Abstract

A series of 2,4-diaminopyridine derivatives was synthesized and evaluated as potential candidates for neuropeptide Y (NPY) Y1 receptor positron emission tomography (PET) tracers. Derivatives bearing substitutions allowing reliable access to radiolabeling were designed, focusing on Y1 binding affinity and lipophilicity. The advanced derivatives 2n and 2o were identified as promising PET tracer candidates.

MeSH terms

4-Aminopyridine / analogs & derivatives*
4-Aminopyridine / chemical synthesis
4-Aminopyridine / chemistry
Aminopyridines / chemical synthesis*
Aminopyridines / chemistry
Animals
CHO Cells
Cell Line
Cricetinae
Cricetulus
Humans
Positron-Emission Tomography*
Receptors, Neuropeptide Y / metabolism*
Recombinant Proteins / metabolism
Structure-Activity Relationship
Thiazoles / chemical synthesis*
Thiazoles / chemistry

Substances

Aminopyridines
Receptors, Neuropeptide Y
Recombinant Proteins
Thiazoles
neuropeptide Y-Y1 receptor
2,4-diaminopyridine
4-Aminopyridine