{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:09Z","timestamp":1760060709806,"version":"build-2065373602"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2024MB099"],"award-info":[{"award-number":["ZR2024MB099"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The development of novel active molecules with a clear target has always been an urgent need for the treatment of epilepsy. Previously, we reported 2\u2010(2\u2010fluorophenyl)\u20105\u2010phenyl\u20107\u2010propyl\u2010[1,2,4]triazolo[1,5\u2010a]pyrimidine (<jats:bold>10C<\/jats:bold>) as a selective and positive modulator of GABA<jats:sub>A<\/jats:sub> receptors, which exhibited excellent antiepileptic activity in mice with an ED<jats:sub>50<\/jats:sub> value of 8.51\u2009mg\/kg. However, the pharmacokinetics (PK) profiles of this compound remain unclear. In this study, <jats:bold>10C<\/jats:bold> and four analogs (<jats:bold>10A<\/jats:bold>, <jats:bold>10B<\/jats:bold>, <jats:bold>10D<\/jats:bold>, and <jats:bold>10E<\/jats:bold>) as well as deuterated <jats:bold>10C<\/jats:bold> were synthesized with high efficiency under optimized reaction conditions, and deuterated <jats:bold>10C<\/jats:bold> was employed as an internal standard. The concentrations of the five compounds in rat plasma and of <jats:bold>10C<\/jats:bold> in tissue homogenate were assayed using a liquid chromatography\u2013tandem mass spectrometry (LC\u2010MS\/MS) method. The results indicated that, compared to the other four analogs, <jats:bold>10C<\/jats:bold> exhibited the highest drug concentration in rat plasma at the same dosage, which provides a good explanation for its superior antiepileptic activity compared to the other four analogs. Following intraperitoneal injection, <jats:bold>10C<\/jats:bold> displayed favorable pharmacokinetic characteristics (<jats:italic>F<\/jats:italic>\u2009=\u200941%) and excellent brain penetration potency (B\/<jats:italic>P<\/jats:italic>\u2009=\u20091.9). Overall, compound <jats:bold>10C<\/jats:bold> is a promising lead for the research and development of new small\u2010molecule therapeutics for epilepsy.<\/jats:p>","DOI":"10.1002\/bmc.70088","type":"journal-article","created":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T23:20:51Z","timestamp":1745191251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics and Tissue Distribution Study for 2\u2010(2\u2010Fluorophenyl)\u20105\u2010Phenyl\u20107\u2010Alkoxy\u2010 [1,2,4]Triazole[1,5\u2010a]Pyrimidine Antiepileptic Compounds in Rats"],"prefix":"10.1002","volume":"39","author":[{"given":"Han","family":"Liang","sequence":"first","affiliation":[{"name":"College of Chemical Engineering Qingdao University of Science and Technology  Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranran","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Chemical 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