Design, synthesis and evaluation of a novel cyclohexanamine class of neuropeptide Y Y1 receptor antagonists

Kaimei Cho; Makoto Ando; Kensuke Kobayashi; Hiroshi Miyazoe; Toshiaki Tsujino; Sayaka Ito; Tomoki Suzuki; Takeshi Tanaka; Shigeru Tokita; Nagaaki Sato

doi:10.1016/j.bmcl.2009.06.050

Design, synthesis and evaluation of a novel cyclohexanamine class of neuropeptide Y Y1 receptor antagonists

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4781-5. doi: 10.1016/j.bmcl.2009.06.050. Epub 2009 Jun 17.

Authors

Kaimei Cho¹, Makoto Ando, Kensuke Kobayashi, Hiroshi Miyazoe, Toshiaki Tsujino, Sayaka Ito, Tomoki Suzuki, Takeshi Tanaka, Shigeru Tokita, Nagaaki Sato

Affiliation

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

PMID: 19596193
DOI: 10.1016/j.bmcl.2009.06.050

Abstract

A novel series of cyclohexanamine derivatives was designed and synthesized as potent and selective human neuropeptide Y Y1 receptor antagonists. Modification of high-throughput screening hit compound 1 resulted in the identification of compound 3i, which displays potent Y1 activity and good selectivity towards hERG K(+) channel and serotonin transporter.

MeSH terms

Cell Line
Cyclohexylamines / chemical synthesis
Cyclohexylamines / chemistry*
Cyclohexylamines / pharmacology
Drug Design
Ether-A-Go-Go Potassium Channels / metabolism
Humans
Receptors, Neuropeptide Y / antagonists & inhibitors*
Receptors, Neuropeptide Y / metabolism
Serotonin / metabolism
Structure-Activity Relationship

Substances

Cyclohexylamines
Ether-A-Go-Go Potassium Channels
KCNH1 protein, human
Receptors, Neuropeptide Y
neuropeptide Y-Y1 receptor
Serotonin