{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:10:06Z","timestamp":1780492206185,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,24]],"date-time":"2021-07-24T00:00:00Z","timestamp":1627084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI16\/01041"],"award-info":[{"award-number":["PI16\/01041"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01724"],"award-info":[{"award-number":["PI19\/01724"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In excitable cells, mitochondria play a key role in the regulation of the cytosolic Ca2+ levels. A dysregulation of the mitochondrial Ca2+ buffering machinery derives in serious pathologies, where neurodegenerative diseases highlight. Since the mitochondrial Na+\/Ca2+ exchanger (NCLX) is the principal efflux pathway of Ca2+ to the cytosol, drugs capable of blocking NCLX have been proposed to act as neuroprotectants in neuronal damage scenarios exacerbated by Ca2+ overload. In our search of optimized NCLX blockers with augmented drug-likeness, we herein describe the synthesis and pharmacological characterization of new benzothiazepines analogues to the first-in-class NCLX blocker CGP37157 and its further derivative ITH12575, synthesized by our research group. As a result, we found two new compounds with an increased neuroprotective activity, neuronal Ca2+ regulatory activity and improved drug-likeness and pharmacokinetic properties, such as clog p or brain permeability, measured by PAMPA experiments.<\/jats:p>","DOI":"10.3390\/molecules26154473","type":"journal-article","created":{"date-parts":[[2021,7,25]],"date-time":"2021-07-25T22:07:00Z","timestamp":1627250820000},"page":"4473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Synthesis and Biological Assessment of 4,1-Benzothiazepines with Neuroprotective Activity on the Ca2+ Overload for the Treatment of Neurodegenerative Diseases and Stroke"],"prefix":"10.3390","volume":"26","author":[{"given":"Luc\u00eda","family":"Viejo","sequence":"first","affiliation":[{"name":"Instituto-Fundaci\u00f3n Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/Arzobispo Morcillo, 4, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Servicio de Farmacolog\u00eda Cl\u00ednica, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3005-2149","authenticated-orcid":false,"given":"Marcos","family":"Rubio-Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto-Fundaci\u00f3n Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel L.","family":"Arribas","sequence":"additional","affiliation":[{"name":"Instituto-Fundaci\u00f3n Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Moreno-Castro","sequence":"additional","affiliation":[{"name":"Instituto-Fundaci\u00f3n Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"P\u00e9rez-Mar\u00edn","sequence":"additional","affiliation":[{"name":"Instituto-Fundaci\u00f3n Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Braun-Cornejo","sequence":"additional","affiliation":[{"name":"Instituto-Fundaci\u00f3n Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-9785","authenticated-orcid":false,"given":"Mart\u00edn","family":"Estrada-Valencia","sequence":"additional","affiliation":[{"name":"Instituto-Fundaci\u00f3n Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/Arzobispo Morcillo, 4, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-7589","authenticated-orcid":false,"given":"Crist\u00f3bal","family":"de los R\u00edos","sequence":"additional","affiliation":[{"name":"Instituto-Fundaci\u00f3n Te\u00f3filo Hernando and Departamento de Farmacolog\u00eda y Terap\u00e9utica, Universidad Aut\u00f3noma de Madrid, C\/Arzobispo Morcillo, 4, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria, Servicio de Farmacolog\u00eda Cl\u00ednica, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrm1155","article-title":"Calcium Signalling: Dynamics, Homeostasis and Remodelling","volume":"4","author":"Berridge","year":"2003","journal-title":"Nat. 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