{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:37:37Z","timestamp":1783723057220,"version":"3.55.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T00:00:00Z","timestamp":1153094400000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>Loperamide is a well\u2010known peripherally acting opiate used for the treatment of diarrhoea. To gain more knowledge on the structure\u2013activity relationships of antidiarrhoeal drugs and to develop new active molecules, a series of aryl\u2010cyano\u2010piperidinoalkyl\u2010thiazolidinones related to Loperamide was synthesized and screened for antidiarrhoeal activity in mice by castor oil test. To characterize the potency and toxicity of the synthesized compounds ED<jats:sub>50<\/jats:sub> and LD<jats:sub>50<\/jats:sub> values were also determined. The thiazolidinones <jats:bold>2<\/jats:bold>\u2013<jats:bold>6<\/jats:bold> displayed antidiarrhoeal activity at doses ranging between 15 and 82\u2003mg\/kg. Although the results show that the synthesized compounds are 15\u2010 to 80\u2010fold less active respect to the reference compound, Loperamide, they are much less toxic (\u22651000\u2003mg\/kg and 108.9\u2003mg\/kg, respectively). Besides, to evaluate the involvement of opioid receptors in antidiarrhoeal activity, Naloxone was administered prior to test the 2\u2010phenyl\u20103\u2010{2\u2010[(4\u2010phenyl\u20104\u2010cyano)piperidino]ethyl}\u20101,3\u2010thiazolidin\u20104\u2010one (<jats:bold>2<\/jats:bold>), the more active compound of this series. The results obtained by this study, suggest that the antidiarrhoeal activity of this series of thiazolidinone derivatives could involve the opioid receptors.<\/jats:p>","DOI":"10.1111\/j.1747-0285.2006.00399.x","type":"journal-article","created":{"date-parts":[[2006,7,17]],"date-time":"2006-07-17T10:17:45Z","timestamp":1153131465000},"page":"432-436","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis and Pharmacological Activity of 2\u2010(substituted)\u20103\u2010{2\u2010[(4\u2010phenyl\u20104\u2010cyano)piperidino]ethyl}\u20101,3\u2010thiazolidin\u20104\u2010ones"],"prefix":"10.1111","volume":"67","author":[{"given":"Orazio","family":"Mazzoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Mazzella","family":"Di Bosco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Grieco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ettore","family":"Novellino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Bertamino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Borrelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Capasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Vittoria","family":"Diurno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,17]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(87)90677-1"},{"key":"e_1_2_5_3_2","first-page":"1641","article-title":"Loperamide (R\u201018533), a novel type of antidiarrheal agent: Part 3. In vitro studies on the peristaltic reflex and other experiments on isolated tissues","volume":"24","author":"Van Neuten J.M.","year":"1974","journal-title":"Arzeinmittelforschung"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.23.040183.001431"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0950-3528(88)90024-3"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198224050-00005"},{"key":"e_1_2_5_7_2","first-page":"566","volume-title":"Goodman & Gilman's The Pharmacological Basis of Therapeutics","author":"Gutstein H.B.","year":"2003"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.109156"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1996.tb03966.x"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)90261-5"},{"key":"e_1_2_5_11_2","first-page":"1633","article-title":"Loperamide (R\u201018533), a novel type of antidiarrheal agent: Part 1. 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