{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T19:47:32Z","timestamp":1778701652481,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005289","name":"National Institute of Justice","doi-asserted-by":"publisher","award":["2016\u2010R2\u2010CX\u20100059"],"award-info":[{"award-number":["2016\u2010R2\u2010CX\u20100059"]}],"id":[{"id":"10.13039\/100005289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Forensic Sciences"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Analogs of non\u2010fentanyl novel synthetic opioids (NSO) with modifications that fall outside of established structure\u2013activity relationships (SARs) for that class of drugs create the question whether or not it should be considered an analog, as defined by 21\u2009U.S.C. \u00a7802(32)(A), which is important for its inclusion in the US system of drug scheduling. AH\u20107921 is a US Schedule I drug and an example of the 1\u2010benzamidomethyl\u20101\u2010cyclohexyldialkylamine class of NSO. The SARs regarding substitution of the central cyclohexyl ring have not been well characterized in the literature. Therefore, in order to expand the SAR surrounding AH\u20107921 analogs, <jats:italic>trans<\/jats:italic>\u20103,4\u2010dichloro\u2010<jats:italic>N<\/jats:italic>\u2010[[1\u2010(dimethylamino)\u20104\u2010phenylcyclohexyl]methyl]\u2010benzamide (AP01; 4\u2010phenyl\u2010AH\u20107921) has been synthesized, analytically characterized, and tested in vitro and in vivo pharmacologically. Using methods described in the original patents for this class of NSO, it was found that the single <jats:italic>trans<\/jats:italic> geometric isomer was obtained. The proton nuclear magnetic resonance, mass spectrum, infrared spectrum, and Raman spectrum are reported along with the melting point of the hydrochloride salt. In vitro binding to a battery of 43 central nervous system receptors showed it to be a high\u2010affinity \u03bc\u2010opioid receptor (MOR) and \u03ba\u2010opioid receptor (KOR) ligand (60\u2009nM and 34\u2009nM, respectively). AP01 also had a 4\u00a0nM affinity for the serotonin transporter (SERT), which is a higher level of potency at this receptor than most other opioids. In rats, it exhibited antinociception in the acetic acid writhing test. Therefore, the 4\u2010phenyl modification results in an active NSO, but carries with it potential toxicities beyond those expected for currently approved opioid drugs.<\/jats:p>","DOI":"10.1111\/1556-4029.15222","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T18:34:22Z","timestamp":1677090862000},"page":"978-989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synthesis, structure, in vitro pharmacology, and in vivo activity of <i>trans<\/i>\u20103,<scp>4\u2010dichloro\u2010<i>N<\/i><\/scp>\u2010[[1\u2010(dimethylamino)\u20104\u2010phenylcyclohexyl]methyl]\u2010benzamide (<scp>AP01<\/scp>; <scp>4\u2010phenyl\u2010AH<\/scp>\u20107921), a novel mixed \u03bc\u2010\/\u03ba\u2010opioid"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3773-2523","authenticated-orcid":false,"given":"John 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