title: Synthesis, characterization and biological evaluation of benzothiazoles and tetrahydrobenzothiazoles bearing urea or thiourea moieties as vasorelaxants and inhibitors of the insulin releasing process.
abstract: A series of 1,3-benzothiazoles (series I) and 4,5,6,7-tetrahydro-1,3-benzothiazoles (series II) bearing an urea or a thiourea moiety at the 2-position were synthesized and tested as myorelaxants and inhibitors of insulin secretion. Several compounds (i.e. 13u and 13v) from series I showed a marked myorelaxant activity. Benzothiazoles bearing a strong electron withdrawing group (NO2, CN) at the 6-position and an alkyl group linked to the urea or the thiourea function at the 2-position were found to be the most potent compounds. The weak vasorelaxant activity of series II compounds evidenced the necessity of the presence of a complete aromatic heterocyclic system. The myorelaxant activity of some active compounds was reduced when measured on aorta rings precontracted by 80 mM KCl or by 30 mM KCl in the presence of 10 μM glibenclamide, suggesting the involvement of KATP channels in the vasorelaxant effect. Some compounds of series I tested on rat pancreatic islets provoked a marked inhibition of insulin secretion, among which 13a exhibited a clear tissue selectivity for pancreatic β-cells.
authors.affiliation: Laboratoire de Phytochimie et de Pharmacologie, Département de Chimie, Faculté des Sciences Exactes et Informatique, Université Mohamed Seddik Ben Yahia Jijel, B.P. 98 Ouled Aissa, 18000 Jijel, Algeria.
authors.forename: Kamel
authors.initials: K
authors.lastname: Harrouche
authors.affiliation: Laboratoire de Chimie Pharmaceutique, Center for Interdisciplinary Research on Medicines (CIRM), Université de Liège, 1, Avenue de l'Hôpital, B-4000 Liège, Belgium.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Renard
authors.affiliation: Laboratoire de Phytochimie et de Pharmacologie, Département de Chimie, Faculté des Sciences Exactes et Informatique, Université Mohamed Seddik Ben Yahia Jijel, B.P. 98 Ouled Aissa, 18000 Jijel, Algeria.
authors.forename: Nafila
authors.initials: N
authors.lastname: Bouider
authors.affiliation: Laboratoire de Chimie Pharmaceutique, Center for Interdisciplinary Research on Medicines (CIRM), Université de Liège, 1, Avenue de l'Hôpital, B-4000 Liège, Belgium.
authors.forename: Pascal
authors.initials: P
authors.lastname: de Tullio
authors.affiliation: Laboratoire de Chimie Pharmaceutique, Center for Interdisciplinary Research on Medicines (CIRM), Université de Liège, 1, Avenue de l'Hôpital, B-4000 Liège, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Goffin
authors.affiliation: Laboratoire de Physiologie et Pharmacologie, Université Libre de Bruxelles, Faculté de Médecine, 808, Route de Lennik, B-1070 Bruxelles, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lebrun
authors.affiliation: Laboratoire "Hypoxie: Physiopathologie Cardiovasculaire et Respiratoire" (HP2), INSERM U1042-Université Grenoble Alpes, F-38042 La Tronche, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Faury
authors.affiliation: Laboratoire de Chimie Pharmaceutique, Center for Interdisciplinary Research on Medicines (CIRM), Université de Liège, 1, Avenue de l'Hôpital, B-4000 Liège, Belgium. Electronic address: b.pirotte@ulg.ac.be.
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirotte
authors.affiliation: Laboratoire de Phytochimie et de Pharmacologie, Département de Chimie, Faculté des Sciences Exactes et Informatique, Université Mohamed Seddik Ben Yahia Jijel, B.P. 98 Ouled Aissa, 18000 Jijel, Algeria.
authors.forename: Smail
authors.initials: S
authors.lastname: Khelili
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000737:chemistry*; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D052160:Benzothiazoles; D007328:Insulin; D014665:Vasodilator Agents; D014508:Urea
keywords: Benzothiadiazine; Benzothiazole; Diazoxide; K(ATP) channel; Pinacidil; Potassium channel openers