Synthesis, characterization and biological evaluation of benzothiazoles and tetrahydrobenzothiazoles bearing urea or thiourea moieties as vasorelaxants and inhibitors of the insulin releasing process

Article abstract of DOI:10.1016/j.ejmech.2016.03.028

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 K_ATP 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.