Referenced in: none

Automatically associated channels: Kv11.1

Title: Synthesis and biological evaluation of imidazole derivatives as novel NOP/ORL1 receptor antagonists: exploration and optimization of alternative pyrazole structure.

Authors: Yuichi Sugimoto, Kensuke Kobayashi, Masanori Asai, Akio Ohno, Koji Yamada, Satoshi Ozaki, Hisashi Ohta, Osamu Okamoto

Journal, date & volume: Bioorg. Med. Chem. Lett., 2009 Aug 15 , 19, 4611-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19604695

Abstract
Nonpeptidic small-molecule NOP/ORL1 receptor antagonists with an imidazole scaffold were designed and synthesized to investigate alternatives to the pyrazole analog. Systematic modification of the original pyrazole lead [Kobayashi et al., Bioorg. Med. Chem. Lett.2009, 19, 3627; Kobayashi et al., Bioorg. Med. Chem. Lett., in press] to change the heterocyclic core, substituted side chain, and pendant functional group demonstrated that examining the structure-activity relationship for novel templates allowed the identification of potent, fully substituted 4-aminomethyl-1H-imidazole and 2-aminomethyl-1H-imidazole. These compounds exhibited excellent potency for ORL1 receptor with minimal P-gp efflux and/or reduced hERG affinity.