Substituted Triazoles as novel Kappa Opioid-selective Ligands Useful in the Treatment of Disease

Track Code: 
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.
KORs have been implicated in patients suffering from addiction, depression, pain relief and immune response. It is believed that small molecules that are capable of modulating the KOR can be utilized as tools to combat the aforementioned ailments. It is to this end that the inventors took to find a new class of KOR agonists and antagonists. The current invention utilized high-throughput screening (HTS) to find chemotypes that bind to KOR. The target molecules were then modified and the binding affinity for each of the analogs is determined. The chemotypes identified are easily modifiable so that different variations can be used in a situation dependent manner.
The primary application is to use the small molecules to treat addiction, depression, pain relief, and/or immune response.
How it works: 
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.
Why it is better: 
The ease at which the chemotypes are altered allow for quick synthesis and testing for binding affinity.
Other Applications: 
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.
Licensing Associate: 
Aswini Betha, PhD · · 913-588-5713
Jeffrey Aube
Kevin J. Frankowski
Kevin Li
Thomas E. Prisinzano
Partha Ghosh
David Whipple
US 9,345,703
US 9,540,375