Matos, Maria JoãoUriarte Villares, EugenioSeoane Lloves, NuriaPicos Martínez, AitorGil Longo, JoséCampos Toimil, Manuel2023-01-022023-01-022022Chem Med Chem 2022,17, e20220047. https://doi.org/10.1002/cmdc.2022004761860-7179http://hdl.handle.net/10347/29703Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate−coumarins and evaluated their vasorelaxant activity in contraction-relaxation studies using rat aorta rings precontracted with phenylephrine or by depolarization with a high concentration of potassium chloride. Four of the new compounds were able to relax smooth vascular muscle with a similar profile and potency to glyceryl trinitrate (IC50=12.73 nM) and sodium nitroprusside (IC50=4.32 nM). Coumarin-7-yl-methyl nitrate (4), the best compound within the series, was able to relax smooth vascular muscle in the low nanomolar range (IC50=1.92 nM). The mechanisms of action have been explored, being the activation of sGC and the opening of K+ channels involved. Our studies indicate that the new nitrate derivatives are reversible and not deleterious for aortic rings, suggesting that these compounds have a potential interest for the development of new and highly efficient vasodilator drugseng© 2022 The Authors.ChemMedChem published by Wiley-VCHGmbH.This is an open access article under the terms of the CreativeCommonsAttributionNon-CommercialNoDerivsLicense,which permits use and distributionin any medium,provided the original work is properly cited,the use is non-commercial and no modification sor adaptations are madeAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Nitrate−coumarinsVasorelaxationNitroglycerinSodium nitroprussideNitric oxidejournal article10.1002/cmdc.2022004761860-7187open access