{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T03:33:20Z","timestamp":1764646400802,"version":"build-2065373602"},"reference-count":35,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431B 2020\/26"],"award-info":[{"award-number":["ED431B 2020\/26"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2022,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate\u2212coumarins and evaluated their vasorelaxant activity in contraction\u2010relaxation 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 (IC<jats:sub>50<\/jats:sub>=12.73\u2005nM) and sodium nitroprusside (IC<jats:sub>50<\/jats:sub>=4.32\u2005nM). Coumarin\u20107\u2010yl\u2010methyl nitrate (<jats:bold>4<\/jats:bold>), the best compound within the series, was able to relax smooth vascular muscle in the low nanomolar range (IC<jats:sub>50<\/jats:sub>=1.92\u2005nM). The mechanisms of action have been explored, being the activation of sGC and the opening of K<jats:sup>+<\/jats:sup> 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 drugs.<\/jats:p>","DOI":"10.1002\/cmdc.202200476","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T22:18:27Z","timestamp":1663280307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis and Vasorelaxant Activity of Nitrate\u2212Coumarin Derivatives"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-8299","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Matos","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Facultade de Farmacia Universidade Santiago de Compostela  15782 Santiago de Compostela Spain"},{"name":"CIQUP\/Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias Universidade do Porto  4169-007 Porto Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6218-2899","authenticated-orcid":false,"given":"Eugenio","family":"Uriarte","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Facultade de Farmacia Universidade Santiago de Compostela  15782 Santiago de Compostela Spain"},{"name":"Instituto de Ciencias Qu\u00edmicas Aplicadas Universidad Aut\u00f3noma de Chile  7500912 Santiago Chile"}]},{"given":"Nuria","family":"Seoane","sequence":"additional","affiliation":[{"name":"Physiology and Pharmacology of Chronic Diseases (FIFAEC) Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela  Santiago de Compostela Spain"}]},{"given":"Aitor","family":"Picos","sequence":"additional","affiliation":[{"name":"Physiology and Pharmacology of Chronic Diseases (FIFAEC) Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela  Santiago de Compostela Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7728-7140","authenticated-orcid":false,"given":"Jos\u00e9","family":"Gil\u2010Longo","sequence":"additional","affiliation":[{"name":"Physiology and Pharmacology of Chronic Diseases (FIFAEC) Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela  Santiago de Compostela Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3674-3749","authenticated-orcid":false,"given":"Manuel","family":"Campos\u2010Toimil","sequence":"additional","affiliation":[{"name":"Physiology and Pharmacology of Chronic Diseases (FIFAEC) Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela  Santiago de Compostela Spain"}]}],"member":"311","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212166"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/2045-9912.273957"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10101041"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.09.1064"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6376"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216581"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm049857n"},{"volume-title":"Sodium Nitroprusside.","year":"2022","author":"Holme M. R.","key":"e_1_2_8_8_1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm801496u"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.103964"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201000210"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2019.e01552"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.09.012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/11795514211042023"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5985255"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.174867"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.09.100"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2021.104947"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.03.010"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(02)00015-X"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2005.10.013"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules15010270"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2062979"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.08.037"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1218835"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/C1MD00221J"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.04.085"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh0102.102330"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1159\/000174612"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199609000-00004"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708615105"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.56.2.243"},{"key":"e_1_2_8_33_1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S0022-3565(24)35346-7","volume":"292","author":"Leo Tseng C.","year":"2000","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2038"},{"key":"e_1_2_8_35_1","first-page":"181","volume":"19","author":"Cook N.","year":"1990","journal-title":"Pharm. Unserer Zeit"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202200476","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202200476","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202200476","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T16:51:33Z","timestamp":1760287893000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202200476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":35,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2022,11,4]]}},"alternative-id":["10.1002\/cmdc.202200476"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202200476","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"type":"print","value":"1860-7179"},{"type":"electronic","value":"1860-7187"}],"subject":[],"published":{"date-parts":[[2022,10,13]]},"assertion":[{"value":"2022-09-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202200476"}}