title: Synthesis and pharmacological activity of 2-(substituted)-3-{2-[(4-phenyl-4-cyano)piperidino]ethyl}-1,3-thiazolidin-4-ones.
abstract: Loperamide is a well-known peripherally acting opiate used for the treatment of diarrhoea. To gain more knowledge on the structure-activity relationships of antidiarrhoeal drugs and to develop new active molecules, a series of aryl-cyano-piperidinoalkyl-thiazolidinones 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 ED50 and LD50 values were also determined. The thiazolidinones 2-6 displayed antidiarrhoeal activity at doses ranging between 15 and 82 mg/kg. Although the results show that the synthesized compounds are 15- to 80-fold less active respect to the reference compound, Loperamide, they are much less toxic (> or = 1000 mg/kg and 108.9 mg/kg, respectively). Besides, to evaluate the involvement of opioid receptors in antidiarrhoeal activity, Naloxone was administered prior to test the 2-phenyl-3-{2-[(4-phenyl-4-cyano)piperidino]ethyl}-1,3-thiazolidin-4-one (2), 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.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, via D. Montesano 49, 80131 Napoli, Italia.
authors.forename: Orazio
authors.initials: O
authors.lastname: Mazzoni
authors.forename: Antonio Mazzella
authors.initials: AM
authors.lastname: di Bosco
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capasso
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Diurno
mesh_terms: D000818:Animals; D000930:Antidiarrheals / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002368:Castor Oil / Q000633:toxicity; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy*; D008139:Loperamide / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D008958:Models, Molecular; D009270:Naloxone / Q000494:pharmacology; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000930:Antidiarrheals; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; D009270:Naloxone; D008139:Loperamide; D002368:Castor Oil