Synthesis, Spectroscopy and Pharmacology of Emerging Synthetic Opioids

As submitted by the applicant: The latest wave of synthetic drugs of abuse dates from about 2008 with the appearance of synthetic cannabinoids and soon afterwards, stimulants, termed ‘bath salts’. What is new from previous outbreaks of synthetic drugs is the rapidity at which new diverse structural types of compounds appear in an attempt to evade drug scheduling laws. This pace of change has presented a significant challenge to law enforcement. With the ongoing opiate addiction crisis and the relatively recent appearance of several synthetic opioids, particularly AH-7921, as part of this recent synthetic drug wave, the purpose of this proposal is to suggest that it may be reasonable to expect a similar onslaught of multiple newer synthetic opioids. Despite a long history of these compounds, these structurally simple core structures that are distinct from currently scheduled compounds and provide an enticing opportunity for the marketing of ‘legal highs’ within the opioid class. We propose to use combinatorial methods to rapidly synthesize and characterize a series of AH-7921 and closely related bromadol derivatives to make these available for spectroscopic characterization and provide in vitro functional testing using the cloned human-opioid receptor, which has not been reported for these analog. Note: This project contains a research and/or development component, as defined in applicable law. ca/ncf