Fluorinated 3,4-Dihydro-2H-1,4-Benzothiazin- 1,1-Dioxide Derivatives with Antiarrhythmic and Hypertensive Effects

Abstract

A series of fluorinated 3,4-dihydro-2H-1,4-benzothiazine derivatives was synthesized starting from pentafluorobenzoic acid and 2-mercaptoethanol via aromatic nucleophilic substitution of fluorine atoms. They were characterized by spectral methods, X-ray diffraction analysis, and screened for the cardiotropic activity in vivo on mature male rats of line Wistar. The presence of a possible antiarrhythmic activity in the selected derivatives was tested, as was the effect on blood pressure in widely accepted models of arrhythmia. It was found that this series of chemical compounds has an antiarrhythmic effect and causes a monotonic increase in blood pressure within 3-5min. As the most promising agents were selected 5,7difluoro-3,4-dihydro-2H-benzo[1,4]thiazine-1,1-dioxide derivatives 3c and 5, containing a cyclopentylamine fragment at position 8.