Program Director/Principal Invesligator (Last. First, IVIiddle): Bannister, ThomaS, D Core APROJECT 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 yetreported, and have developed efficient synthetic routes for their preparation. Core A will provide medicinalchemistry support for all other cores. The chemists in Core A will further optimize the preparation of potentialprobes of a multigram scale, providing probe candidates and literature comparison compounds to othercores as needed. In addition, we will use in vitro analysis of compound properties to identify appropriatecompounds and suitable salt forms and formulations for animal dosing by other cores. This core isresponsible for giving out compounds to all project members and is deemed a necessary core for all projectteams to perform their research. The project teams will request compound from the core prior to performingtheir 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 theybe needed, so that no project team is unable to perform their work.
Agonists of the NOP receptor have been proposed as potential probes to modulate behavior associated withcocaine addiction. Core A, providing medicinal chemistry support and in vitro assessment of compoundproperties, is central to the combined objectives of the program, which can only succeed with a dependableand 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.
| Pan, Xiaohong; Yang, Chunying; Cleveland, John L et al. (2016) Synthesis and Cytoxicity of Sempervirine and Analogues. J Org Chem 81:2194-200 |
| Pan, Xiaohong; Bannister, Thomas D (2014) Sequential Sonagashira and Larock indole synthesis reactions in a general strategy to prepare biologically active ?-carboline-containing alkaloids. Org Lett 16:6124-7 |
| Andero, Raül; Brothers, Shaun P; Jovanovic, Tanja et al. (2013) Amygdala-dependent fear is regulated by Oprl1 in mice and humans with PTSD. Sci Transl Med 5:188ra73 |
