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Antagonists such as UBP1700 and positive allosteric modulators including PYD-106 and 3-acylamino-2-aminopropionic acid derivatives such as UA3-10 ((\n                    <jats:italic>R<\/jats:italic>\n                    )-2-amino-3-{[5-(2-bromophenyl)thiophen-2-yl]carboxamido}propionic acid) represent promising tool compounds to investigate the role of GluN2C-containing NMDA receptors in the signal transduction in the brain. However, due to its high polarity the bioavailability and CNS penetration of the amino acid UA3-10 are expected to be rather low. Herein, three ester prodrugs\n                    <jats:bold>12a<\/jats:bold>\n                    \u2013\n                    <jats:bold>c<\/jats:bold>\n                    of the NMDA receptor glycine site agonist UA3-10 were prepared and pharmacokinetically characterized. The esters\n                    <jats:bold>12a<\/jats:bold>\n                    \u2013\n                    <jats:bold>c<\/jats:bold>\n                    showed higher lipophilicity (higher log\n                    <jats:italic>D<\/jats:italic>\n                    <jats:sub>7.4<\/jats:sub>\n                    values) than the acid UA3-10 but almost the same binding at human serum albumin. The acid UA3-10 was rather stable upon incubation with mouse liver microsomes and NADPH, but the esters\n                    <jats:bold>12a<\/jats:bold>\n                    \u2013\n                    <jats:bold>c<\/jats:bold>\n                    were fast hydrolyzed to afford the acid UA3-10. Incubation with pig liver esterase and mouse serum led to rapid hydrolysis of the esters\n                    <jats:bold>12a<\/jats:bold>\n                    \u2013\n                    <jats:bold>c<\/jats:bold>\n                    . The isopropyl ester\n                    <jats:bold>12c<\/jats:bold>\n                    showed a promising log\n                    <jats:italic>D<\/jats:italic>\n                    <jats:sub>7.4<\/jats:sub>\n                    value of 3.57 and the highest stability in the presence of pig liver esterase and mouse serum. These results demonstrate that ester prodrugs of UA3-10 can potentially afford improved bioavailability and CNS penetration.\n                  <\/jats:p>","DOI":"10.1515\/hsz-2022-0229","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T11:16:35Z","timestamp":1669374995000},"page":"255-265","source":"Crossref","is-referenced-by-count":4,"title":["<i>In vitro<\/i>\n                    ADME characterization of a very potent 3-acylamino-2-aminopropionic acid-derived GluN2C-NMDA receptor agonist and its ester prodrugs"],"prefix":"10.1515","volume":"404","author":[{"given":"Elena","family":"Bechthold","sequence":"first","affiliation":[{"name":"Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, GRK 2515, Chemical Biology of Ion Channels (Chembion) , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"},{"name":"Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, Institut f\u00fcr Pharmazeutische und Medizinische Chemie , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1536-1231","authenticated-orcid":false,"given":"Lucie","family":"Grey","sequence":"additional","affiliation":[{"name":"Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, Institut f\u00fcr Pharmazeutische und Medizinische Chemie , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Diamant","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology , Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, Institut f\u00fcr Pharmazeutische und Medizinische Chemie , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Steigerwald","sequence":"additional","affiliation":[{"name":"Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, GRK 2515, Chemical Biology of Ion Channels (Chembion) , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"},{"name":"Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, Institut f\u00fcr Pharmazeutische und Medizinische Chemie , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry , Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University , No. 44, Wenhua West Road, Lixia District , Ji\u2019nan , Shandong , 250012 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper B.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Center for Structural and Functional Neuroscience, Center for Biomolecular Structure and Dynamics, Division of Biological Sciences, University of Montana , 32 Campus Drive , Missoula , MT 59812 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennart","family":"Bunch","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology , Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasmus P.","family":"Clausen","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology , Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9030-8417","authenticated-orcid":false,"given":"Bernhard","family":"W\u00fcnsch","sequence":"additional","affiliation":[{"name":"Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, GRK 2515, Chemical Biology of Ion Channels (Chembion) , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"},{"name":"Westf\u00e4lische Wilhelms-Universit\u00e4t M\u00fcnster, Institut f\u00fcr Pharmazeutische und Medizinische Chemie , Corrensstra\u00dfe 48, D-48149 M\u00fcnster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"2023033110335738234_j_hsz-2022-0229_ref_001","doi-asserted-by":"crossref","unstructured":"Bhattacharya, S., Khatri, A., Swanger, S.A., DiRaddo, J.O., Yi, F., Hansen, K.B., Yuan, H., and Traynelis, S.F. 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