Small molecule Nociceptin Receptor Agonists to Treat Cocaine Abuse

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Program Director/Principal Invesligator (Last. First, IVIiddle): Bannister, ThomaS, D Core A PROJECT SUMMARY (See instmctions): Core A. Medicinal Chemistry Core, Director Thomas Bannister. Ph.D. Abstract: We have previously identified NOP agonists with very high selectivity, surpassing those of any ligands yet reported, and have developed efficient synthetic routes for their preparation. Core A will provide medicinal chemistry support for all other cores. The chemists in Core A will further optimize the preparation of potential probes of a multigram scale, providing probe candidates and literature comparison compounds to other cores as needed. In addition, we will use in vitro analysis of compound properties to identify appropriate compounds and suitable salt forms and formulations for animal dosing by other cores. This core is responsible for giving out compounds to all project members and is deemed a necessary core for all project teams to perform their research. The project teams will request compound from the core prior to performing their assessments. The core will keep a minimum of 1 gram of important compounds (SR-8323, SR-8993, SR-9279, etc.) on hand, and be prepared to quickly synthesize any other necessary compounds, should they be needed, so that no project team is unable to perform their work. RELEVANCE (See instructions): Agonists of the NOP receptor have been proposed as potential probes to modulate behavior associated with cocaine addiction. Core A, providing medicinal chemistry support and in vitro assessment of compound properties, is central to the combined objectives of the program, which can only succeed with a dependable and timely supply of probe candidates to the other cores. Four aims are outlined, including scale-up studies, delivery of probe candidates, salt form evaluation, and in vitro assessment of probe properties.