Innovative Medicinal Chemistry Core

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Abstract: Small organic molecules also continue to be of great utility as biological tools for the identification and characterization of new targets and inhibitory or stimulatory mechanisms, as well as for low-cost large-scale therapeutic applications. Our Core provides unique small molecule synthesis and analysis capabilities based on innovative medicinal chemistry and analytical procedures to the CMCR, and we have a successful track record for working synergistically in developing novel tool compounds and therapeutic candidates for radiation mitigation. Our specific aims are: 1. To synthesize labeled (fluorescent-and isotope-labeled) variants of (a) necrostatin-1, (b) MMS350, (c) varespladib, and (d) R-BEL for Projects 1, 3 and 4 as well as Core H. 2. To supply Project 1 and Core G with scaled-up quantities of BODIPY-JP4-039 and MMS-350. 3. To supply Project 2 with lipid mediators, including homologs of cardiolipins. 4. To supply Projects 1, 2 and 3 with (a) imidazole fatty acid derivatives, (b) MitoEbselen-2, and (c) hepoxillin-A3 and analogs thereof; and 5. To perform EPR and HPLC analyses with either direct electrochemical detection of the analytes or, following tissue extraction, FL detection after derivatization with fluorophores.