Identification of a novel and orally available benzimidazole derivative as an NPY Y5 receptor antagonist with in vivo efficacy

Yuusuke Tamura; Naoki Omori; Naoki Kouyama; Yuji Nishiura; Kyouhei Hayashi; Kana Watanabe; Yukari Tanaka; Takeshi Chiba; Hideo Yukioka; Hiroki Sato; Takayuki Okuno

doi:10.1016/j.bmcl.2012.09.025

Identification of a novel and orally available benzimidazole derivative as an NPY Y5 receptor antagonist with in vivo efficacy

Bioorg Med Chem Lett. 2012 Nov 1;22(21):6554-8. doi: 10.1016/j.bmcl.2012.09.025. Epub 2012 Sep 15.

Authors

Yuusuke Tamura¹, Naoki Omori, Naoki Kouyama, Yuji Nishiura, Kyouhei Hayashi, Kana Watanabe, Yukari Tanaka, Takeshi Chiba, Hideo Yukioka, Hiroki Sato, Takayuki Okuno

Affiliation

¹ Medicinal Research Laboratories, Shionogi & Co., Ltd. 1-1, Futabacho 3-chome, Toyonaka, Osaka 561-0825, Japan. yuusuke.tamura@shionogi.co.jp

PMID: 23025998
DOI: 10.1016/j.bmcl.2012.09.025

Abstract

Optimization of lead compound 2 is described, mainly focusing on modification at the C-2 position of the benzimidazole core. Replacement of the phenyl linker of 2 with saturated rings resulted in identification of compound 8b which combines high Y5 receptor binding affinity with a good ADME profile leading to in vivo efficacy.

MeSH terms

Administration, Oral
Animals
Benzimidazoles / chemistry*
Benzimidazoles / pharmacology*
Drug Design
Drug Stability
Humans
Inhibitory Concentration 50
Mice
Mice, Obese
Protein Binding / drug effects
Receptors, Neuropeptide Y / antagonists & inhibitors*
Solubility
Structure-Activity Relationship

Substances

Benzimidazoles
Receptors, Neuropeptide Y
neuropeptide Y5 receptor