{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T05:00:53Z","timestamp":1768539653938,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T00:00:00Z","timestamp":1516665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Research Council of Shahid Beheshti University","award":["600-1858"],"award-info":[{"award-number":["600-1858"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Novel substituted amino acid tethered norsufentanil derivatives were synthesized by the four\u2010component Ugi reaction. Norsufentanil was reacted with succinic anhydride to produce the corresponding carboxylic acid. The resulting carboxylic acid has undergone a multicomponent reaction with different aldehydes, amines, and isocyanides to produce a library of the desired compounds. In all cases, amide bond rotation was observed in the<jats:styled-content style=\"fixed-case\">NMR<\/jats:styled-content>spectra. In vivo analgesic activity of the synthesized compounds was evaluated by a tail flick test. Very encouraging results were obtained for a number of the synthesized products. Some of the synthesized compounds such as<jats:bold>5a<\/jats:bold>,<jats:bold>5b<\/jats:bold>,<jats:bold>5h<\/jats:bold>,<jats:bold>5j<\/jats:bold>, and<jats:bold>5r<\/jats:bold>were found to be more potent than sufentanil, sufentanil citrate, and norsufentanil. Binding modes between the compounds and mu and delta\u2010opioid receptors were studied by molecular docking method. The relationship between the molecular structural features and the analgesic activity was investigated by a quantitative structure\u2013activity relationship model. The results of the molecular modeling studies and the in vivo analgesic activity suggested that the majority of the synthesized compounds were more potent than sufentanil and norsufentanil.<\/jats:p>","DOI":"10.1111\/cbdd.13157","type":"journal-article","created":{"date-parts":[[2017,12,9]],"date-time":"2017-12-09T02:37:14Z","timestamp":1512787034000},"page":"902-914","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis of novel norsufentanil analogs via a four\u2010component Ugi reaction and in vivo, docking, and<scp>QSAR<\/scp>studies of their analgesic activity"],"prefix":"10.1111","volume":"91","author":[{"given":"Majid","family":"Nami","sequence":"first","affiliation":[{"name":"Faculty of Chemistry Shahid Beheshti University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5774-3372","authenticated-orcid":false,"given":"Peyman","family":"Salehi","sequence":"additional","affiliation":[{"name":"Department of Phytochemistry Medicinal Plants and Drugs Research Institute Shahid Beheshti University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoo","family":"Dabiri","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry Shahid Beheshti University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morteza","family":"Bararjanian","sequence":"additional","affiliation":[{"name":"Department of Phytochemistry Medicinal Plants and Drugs Research Institute Shahid Beheshti University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sajjad","family":"Gharaghani","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Drug Design (LBD) Institute of Biochemistry and Biophysics University of Tehran Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Khoramjouy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Al\u2010Harrasi","sequence":"additional","affiliation":[{"name":"UoN Chair of Oman`S Medicinal Plants and Marine Natural University of Nizwa Nizwa Oman"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehrdad","family":"Faizi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.13.215"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198836030-00003"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0885-3924(92)90047-L"},{"key":"e_1_2_8_5_1","unstructured":"J.Mathew J.Kendall\u2010Killgore Methods for the synthesis of alfentanil sufentanil and remifentanil. 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