Substituted Triazoles as novel Kappa Opioid-selective Ligands Useful in the Treatment of Disease
The small molecules in this work represent a novel composition of matter that can be used as either Kappa Opioid Receptor (KOR) agonists or antagonists. Further some of the compounds have been shown to weak agonists making them ideal to explore for the use of addiction.
The primary application is to use the small molecules to treat addiction, depression, pain relief, and/or immune response.
The chemotypes were identified using HTS. These chemotypes were subsequently modified and their binding affinity for KORs was measured.
Presently compounds implicated as KOR agonists or antagonists are extremely complicated compounds that require many synthetic steps to alter. The chemotypes in the present invention have few, if any stereocenters so the synthetic steps required for alteration is significantly minimized.
The ease at which the chemotypes are altered allow for quick synthesis and testing for binding affinity.
The compounds could be radiolabeled to serve as key probes for receptor distribution and internalization studies, as well as probes to map out the contribution of different steps along the β-arrestin mediated signaling pathway in cells.