Discovery of S-777469: an orally available CB2 agonist as an antipruritic agent

Masahide Odan; Natsuki Ishizuka; Yoshiharu Hiramatsu; Masanao Inagaki; Hiroshi Hashizume; Yasuhiko Fujii; Susumu Mitsumori; Yasuhide Morioka; Masahiko Soga; Masashi Deguchi; Kiyoshi Yasui; Akinori Arimura

doi:10.1016/j.bmcl.2012.02.072

Discovery of S-777469: an orally available CB2 agonist as an antipruritic agent

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2803-6. doi: 10.1016/j.bmcl.2012.02.072. Epub 2012 Mar 3.

Authors

Masahide Odan¹, Natsuki Ishizuka, Yoshiharu Hiramatsu, Masanao Inagaki, Hiroshi Hashizume, Yasuhiko Fujii, Susumu Mitsumori, Yasuhide Morioka, Masahiko Soga, Masashi Deguchi, Kiyoshi Yasui, Akinori Arimura

Affiliation

¹ Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd 1-1, Toyonaka, Osaka, Japan. masahide.oodan@shionogi.co.jp

PMID: 22444677
DOI: 10.1016/j.bmcl.2012.02.072

Abstract

The discovery of novel CB2 ligands based on the 3-carbamoyl-2-pyridone derivatives by adjusting the size of side chain at 1-, 5- and 6-position is reported. The structure-activity relationship around this template lead to the identification of S-777469 as a selective CB2 receptor agonist, which exhibited the significant inhibition of scratching induced by Compound 48/80 at 1.0 mg/kg po and 10 mg/kg po (55% and 61%, respectively).

MeSH terms

Administration, Oral
Animals
Antipruritics / administration & dosage
Antipruritics / chemistry*
Antipruritics / pharmacology*
CHO Cells
Cricetinae
Disease Models, Animal
Inhibitory Concentration 50
Ligands
Mice
Mice, Inbred ICR
Molecular Structure
Protein Binding / drug effects
Pyridones / chemical synthesis*
Pyridones / chemistry
Pyridones / pharmacology*
Receptor, Cannabinoid, CB2 / agonists*

Substances

Antipruritics
Ligands
Pyridones
Receptor, Cannabinoid, CB2
S-777469