Synthesis and Evaluation of 3,4-Dihydropyrimidin-2(1H)-ones as Sodium Iodide Symporter Inhibitors
The sodium iodide symporter (NIS) is responsible for the accumulation of iodide in the thyroid gland. This transport process is involved in numerous thyroid dysfunctions and is the basis for human contamination in the case of exposure to radioactive iodine species. 4-Aryl-3,4-dihydropyrimidin-2(1H)-ones were recently discovered by high-throughput screening as the first NIS inhibitors. Described herein are the synthesis and evaluation of 115 derivatives with structural modifications at five key positions on the pyrimidone core. This study provides extensive structure-activity relationships for this new class of inhibitors that will serve as a basis for further development of compounds with invivo efficacy and adequate pharmacokinetic properties. In addition, the SAR investigation provided a more potent compound, which exhibits an IC50 value of 3.2nM in a rat thyroid cell line (FRTL5).
Lacotte, Pierre,Puente, Celine,Ambroise, Yves
supporting information
p. 104 - 111
(2013/03/28)
Synthesis of novel imidazolidine-2,4-dione derivatives as potential antidiabetic agents
A series of novel imidazolidine-2,4-dione derivatives were synthesized and their chemical structures were confirmed by 1H NMR and ESI-MS. The preliminary antidiabetic screening results demonstrated that the compound 3b showed some antidiabetic activity and could acted as lead compound for further design and discovery of antidiabetic agents.