Carbon‐14 radiolabeling and tissue distribution evaluation of MMV390048

Abstract

The antimalarial compound MMV390048 ([ C]-11) was labeled with carbon-14 isotope via a 3-step synthesis. It was obtained in a 15.5% radiochemical overall yield from carbon-14 labeled methyl iodide with a radiochemical purity of >99%. After single oral administration of [ C]-11 to albino and pigmented rats its tissue distribution profile was studied. Tissue distribution results showed high local exposure in the GI tract and excretory organs but low exposure of all other tissues. The radioactivity uptake was higher in the eyes of the pigmented rats than in the eyes of the albino rats at all-time points. The highest accumulation reached in the eyes of the pigmented rats was 0.46% at 6 hours. However, these levels are still very low as compared to the other organs studied. There was very little radioactivity from MMV390048 ([ C]-11) present in the skin of both the albino and pigmented rats. The results obtained are supportive of further development of MMV390048 as a potential antimalarial compound.

CF2H, a Functional Group-Dependent Hydrogen-Bond Donor: Is It a More or Less Lipophilic Bioisostere of OH, SH, and CH3?

“…The latter reagent was also used to synthesize difluoromethylated compound 11 as described in detail in the Experimental Section. The noncommercial sulfoxides 3c , 4c , 5c , and 6c and sulfones 3d , 4d , 5d , and 6d were prepared by oxidation of the corresponding sulfides using previously reported procedures . The noncommercial sulfide 6b and the difluoromethylated compounds 5a , 9 , and 7 were prepared according to previously published methods.…”

The 15th Frank Warren Organic Chemistry Conference

“…In a move away from conventional medicinal chemistry lectures, Dr. Molahleni Sonopo (South African Nuclear Energy Corporation, NECSA) discussed strategies to incorporate 14 C radiolabels into biologically active compounds for ADME investigations …”

Application of Vinamidinium Salt Chemistry for a Palladium Free Synthesis of Anti-Malarial MMV048: A “Bottom-Up” Approach

“…This is a very logical and efficient sequence of bond disconnects, and it excels for a given policy which seeks to provide access to a diverse range of biologically active structures. All syntheses to date have relied upon this approach. , …”