{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:37:47Z","timestamp":1791221867677,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T00:00:00Z","timestamp":1607817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>New indomethacin analogs <jats:bold>4a\u2013g<\/jats:bold>, <jats:bold>5<\/jats:bold>, <jats:bold>6<\/jats:bold>, <jats:bold>8a<\/jats:bold>, and <jats:bold>8b<\/jats:bold> were synthesized to overcome the nonselectivity and ulcer liability of indomethacin. All newly synthesized compounds were more potent against cyclooxygenase 2 (COX\u20102; IC<jats:sub>50<\/jats:sub> value range: 0.09\u20130.4\u2009\u03bc\u041c) as\u00a0compared with celecoxib (IC<jats:sub>50<\/jats:sub>\u2009=\u20090.89\u2009\u03bc\u041c). Compounds <jats:bold>4a<\/jats:bold>, <jats:bold>4b<\/jats:bold>, <jats:bold>4d<\/jats:bold>, <jats:bold>5<\/jats:bold>, and <jats:bold>6<\/jats:bold> showed the highest COX\u20102 selectivity index (SI range\u2009=\u20094.07\u20136.33) as compared with indomethacin (SI\u2009=\u20091.14) and celecoxib (SI\u2009=\u20093.52). Additionally, <jats:bold>4a<\/jats:bold>, <jats:bold>4b<\/jats:bold>, <jats:bold>4d<\/jats:bold>, <jats:bold>5<\/jats:bold>, and <jats:bold>7<\/jats:bold> showed good anti\u2010inflammatory activity with edema inhibition (79.36\u201388.8%), relative to celecoxib (78.96%) and indomethacin (90.43%), after 5\u2009h. Also, ulcerogenic effects and histopathological examination were assessed for the most potent analogs,\u00a0<jats:bold>4b<\/jats:bold>, <jats:bold>4d<\/jats:bold>, <jats:bold>5<\/jats:bold>, and <jats:bold>6<\/jats:bold>, to determine their safety. The results can shed light on indomethacin analog\u00a0<jats:bold>5<\/jats:bold> as a remarkable anti\u2010inflammatory lead compound with a good safety profile (ulcer index\u2009=\u200910.62) close to the nonulcerogenic drug celecoxib (ulcer index\u2009=\u200910.53) and better than indomethacin (ulcer index\u2009=\u200918.50). Docking studies were performed in the COX\u20102 active site for the most active compounds, to test their selectivity and to confirm their mechanism of action.<\/jats:p>","DOI":"10.1002\/ardp.202000328","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T10:34:49Z","timestamp":1607942089000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["New indomethacin analogs as selective COX\u20102 inhibitors: Synthesis, COX\u20101\/2 inhibitory activity, anti\u2010inflammatory, ulcerogenicity, histopathological, and docking studies"],"prefix":"10.1002","volume":"354","author":[{"given":"Khaled R. A.","family":"Abdellatif","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"},{"name":"Department of Pharmaceutical Science Ibn Sina National College for Medical Studies  Jeddah Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman K. A.","family":"Abdelall","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0699-0650","authenticated-orcid":false,"given":"Heba A. 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M.","family":"Abdelgawad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1224398"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-015-1327-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.09.024"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.01.031"},{"key":"e_1_2_8_6_1","first-page":"113","volume":"57","author":"Botting R.","year":"2006","journal-title":"J. Physiol. 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