Identification of novel benzimidazole series of potent and selective ORL1 antagonists

Osamu Okamoto; Kensuke Kobayashi; Hiroshi Kawamoto; Satoru Ito; Atsushi Satoh; Tetsuya Kato; Izumi Yamamoto; Sayaka Mizutani; Masaya Hashimoto; Atsushi Shimizu; Hiroki Sakoh; Yasushi Nagatomi; Yoshikazu Iwasawa; Hiroyuki Takahashi; Yasuyuki Ishii; Satoshi Ozaki; Hisashi Ohta

doi:10.1016/j.bmcl.2008.04.054

Identification of novel benzimidazole series of potent and selective ORL1 antagonists

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3278-81. doi: 10.1016/j.bmcl.2008.04.054. Epub 2008 Apr 25.

Authors

Osamu Okamoto¹, Kensuke Kobayashi, Hiroshi Kawamoto, Satoru Ito, Atsushi Satoh, Tetsuya Kato, Izumi Yamamoto, Sayaka Mizutani, Masaya Hashimoto, Atsushi Shimizu, Hiroki Sakoh, Yasushi Nagatomi, Yoshikazu Iwasawa, Hiroyuki Takahashi, Yasuyuki Ishii, Satoshi Ozaki, Hisashi Ohta

Affiliation

¹ Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd., Okubo-3, Tsukuba, Ibaraki 300-2611, Japan. osamu_okamoto@merck.com

PMID: 18468891
DOI: 10.1016/j.bmcl.2008.04.054

Abstract

Structure-activity studies on benzimidazole lead 1 obtained from library screening led to the discovery of potent and selective ORL1 antagonist 28, 5-chloro-2-[(1-ethyl-1-methylpropyl)thio]-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazole, which is structurally distinct from conventional non-peptide antagonists known to date.

MeSH terms

Benzimidazoles / chemical synthesis*
Benzimidazoles / chemistry
Benzimidazoles / pharmacology*
Combinatorial Chemistry Techniques
Humans
Molecular Structure
Narcotic Antagonists*
Nociceptin Receptor
Receptors, Opioid
Structure-Activity Relationship

Substances

5-chloro-2-((1-ethyl-1-methylpropyl)thio)-6-(4-(2-hydroxyethyl)piperazin-1-yl)-1H-benzimidazole
Benzimidazoles
Narcotic Antagonists
Receptors, Opioid
Nociceptin Receptor
OPRL1 protein, human