{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T09:06:02Z","timestamp":1784106362755,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:p>\n                    GluN2A containing N\u2010methyl\u2010D\u2010aspartate receptors are involved in neuropsychiatric disorders. Studies with GluN2A knockout mice revealed an anxiolytic and antidepressant\u2010like phenotype across multiple behavioral tests and in humans. Despite its relevance, the development of selective GluN2A antagonists has been hindered by challenges in achieving compound specificity and favorable pharmacological profiles. While competitive antagonists show GluN2A preference, negative allosteric modulators like TCN\u2010201 offer superior selectivity but suffer from poor solubility and glycine sensitivity. Subsequent analogues such as MPX\u2010007 showed significant improvements in potency but remained unsuitable for in\u2009vivo use due to their efflux liability, associated with the presence of a sulfonamide moiety as an important pharmacophoric feature. Herein, we report a structurally distinct novel class of GluN2A\u2010selective negative allosteric modulators identified through virtual screening of the MPX\u2010007 binding site and advanced in\u2009vitro profile, with an optimized compound\n                    <jats:bold>6m<\/jats:bold>\n                    , representing a promising and structurally unique tool for advancing mechanistic studies and exploring therapeutic potential targeting GluN2A.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70358","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:14:49Z","timestamp":1783970089000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Class of Novel, Selective, Structurally Distinct GluN2A Negative Allosteric Modulators Through Virtual Screening"],"prefix":"10.1002","volume":"21","author":[{"given":"Carlos M. Mart\u00ednez","family":"Viturro","sequence":"first","affiliation":[{"name":"Johnson &amp; Johnson  Toledo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Neff","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Bembenek","sequence":"additional","affiliation":[{"name":"Denovicon Therapeutics  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-8361","authenticated-orcid":false,"given":"Jose M.","family":"Cid","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson  Toledo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.002451"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802075105"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251915"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13548"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2006.08.011"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3504"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2006.07.016"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1697-04.2004"},{"key":"e_1_2_7_10_1","first-page":"255","article-title":"Role of Distinct NMDA Receptor Subtypes at Central Synapses","volume":"2004","author":"Cull\u2010Candy S. 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