Novel potent vasodilating agents: Evaluation of the activity and potency of LINS01005 and derivatives in rat aorta

Abstract Cardiovascular diseases (CVDs) present high prevalence rates in the current world. It is estimated that approximately one-third of the global deaths are related to CVDs, and thus there is still a need for novel drugs to treat these disorders. We serendipitously discovered that LINS01005 (5a) is a potent vasodilating agent in rat aorta, and therefore a set of analogues were evaluated for the vasodilating potency in Wistar and SHR rat thoracic aorta precontracted with norepinephrine, with endothelium intact (E+) or denuded (E–) aortic rings. Compounds 5a and 5b were the most potent, showing submicromolar potency for endothelium intact vessels (EC50 853 and 941 nM, respectively) and micromolar values for E– vessels (EC50 2.4 and 7.1 µM, respectively). These compounds were indeed significantly more potent vasodilating agents in SHR-derived aortic rings (p