{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T23:58:39Z","timestamp":1782431919508,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007514","name":"Universit\u00e0 di Pisa","doi-asserted-by":"publisher","award":["Fondi di ateneo 2024"],"award-info":[{"award-number":["Fondi di ateneo 2024"]}],"id":[{"id":"10.13039\/501100007514","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":[[2026,4,28]]},"abstract":"<jats:p>\n                    Carbonic anhydrases (CAs) are ubiquitous metalloenzymes that catalyze the interconversion of carbon dioxide and water to bicarbonate and proton. Given CA crucial role in carbon\u2010based life, CA inhibition is a well\u2010known therapeutic strategy for several diseases. However, in recent years, CA activation has emerged as a promising therapeutic approach for neurodegenerative conditions such as Alzheimer's disease, generalized anxiety, phobias and post\u2010traumatic stress disorder. In this study, a new series of amino alcohol oxime ethers was synthesized from hit compound\n                    <jats:bold>A<\/jats:bold>\n                    to enhance its activity and selectivity towards\u00a0four brain hCA isoforms, particularly hCA VII, which plays a key role in regulating neuronal pH related to synaptic plasticity and cognitive performance. Herein, we report a structure\u2013activity relationship analysis to identify compounds that are both potent and selective activators for hCA VII. Among the synthesized derivatives, the morpholino propyl compound\n                    <jats:bold>12<\/jats:bold>\n                    emerged as the most active (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>A<\/jats:sub>\n                    \u2009=\u200972\u2009nM) and selective over other brain isoforms. These results were further supported by in silico studies, which revealed favorable binding interactions at site A due to structural features present in both\n                    <jats:italic>R<\/jats:italic>\n                    and\n                    <jats:italic>S<\/jats:italic>\n                    enantiomers of compound\n                    <jats:bold>12<\/jats:bold>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70272","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:14:37Z","timestamp":1776816877000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A New Series of Amino Alcohol Oxime Ethers as Activators of Human Brain Carbonic Anhydrases: Advances in Selective Activation of Human Carbonic Anhydrase VII"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6810-8110","authenticated-orcid":false,"given":"Camilla","family":"Mangini","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5051-1584","authenticated-orcid":false,"given":"Riccardo Di","family":"Leo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Pisa Italy"},{"name":"Institute of Clinical Physiology National Research Council (CNR)  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3294-3626","authenticated-orcid":false,"given":"Jacopo","family":"Castagnoli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Pisa 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