Discovery of substituted 2,4,4-triarylimidazoline derivatives as potent and selective neuropeptide Y Y5 receptor antagonists

Nagaaki Sato; Makoto Jitsuoka; Shiho Ishikawa; Keita Nagai; Hiroyasu Tsuge; Makoto Ando; Osamu Okamoto; Hisashi Iwaasa; Akira Gomori; Akane Ishihara; Akio Kanatani; Takehiro Fukami

doi:10.1016/j.bmcl.2009.01.101

Discovery of substituted 2,4,4-triarylimidazoline derivatives as potent and selective neuropeptide Y Y5 receptor antagonists

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1670-4. doi: 10.1016/j.bmcl.2009.01.101. Epub 2009 Feb 4.

Authors

Nagaaki Sato¹, Makoto Jitsuoka, Shiho Ishikawa, Keita Nagai, Hiroyasu Tsuge, Makoto Ando, Osamu Okamoto, Hisashi Iwaasa, Akira Gomori, Akane Ishihara, Akio Kanatani, Takehiro Fukami

Affiliation

¹ Tsukuba Research Institute, Merck Research Laboratories, Banyu Pharmaceutical Company, Ltd, 3 Okubo, Tsukuba 300-2611, Japan.

PMID: 19233647
DOI: 10.1016/j.bmcl.2009.01.101

Abstract

Novel imidazoline derivatives were discovered to be potent neuropeptide Y Y5 receptor antagonists. High-throughput screening of Merck sample collections against the human Y5 receptor resulted in the identification of 2,4,4-triphenylimidazoline (1), which had an IC(50) of 54nM. Subsequent optimization led to the identification of several potent derivatives.

MeSH terms

Animals
Brain / metabolism
Carboxylic Acids / chemistry
Cerebrospinal Fluid / metabolism
Chemistry, Pharmaceutical / methods*
Drug Design
Humans
Imidazoles / chemistry*
Inhibitory Concentration 50
Mice
Models, Chemical
Molecular Structure
Receptors, Neuropeptide Y / chemistry*
Structure-Activity Relationship

Substances

Carboxylic Acids
Imidazoles
Receptors, Neuropeptide Y
neuropeptide Y5 receptor