{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:58:20Z","timestamp":1787655500679,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T00:00:00Z","timestamp":1574726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA003910"],"award-info":[{"award-number":["DA003910"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist\/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure\u2013activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogues maintain a KOR agonist\/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist\/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.<\/jats:p>","DOI":"10.3390\/molecules24234302","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T10:57:27Z","timestamp":1574765847000},"page":"4302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Structure\u2013Activity Relationships of 7-Substituted Dimethyltyrosine-Tetrahydroisoquinoline Opioid Peptidomimetics"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6181-3131","authenticated-orcid":false,"given":"Deanna","family":"Montgomery","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica P.","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Edward F. Domino Research Center, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason A.","family":"Baber","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack J.","family":"Twarozynski","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua G.","family":"Hartman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennon J.","family":"Delong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Traynor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Edward F. Domino Research Center, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry I.","family":"Mosberg","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Edward F. Domino Research Center, Medical School, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.1073\/pnas.90.12.5391","article-title":"A brief history of opiates, opioid peptides, and opioid receptors","volume":"90","author":"Brownstein","year":"1993","journal-title":"Proc. Natl. Acad. Sci. 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