Fostedil

Simple and efficient preparation of Fostedil, di-Et 4-(2-benzothiazolyl)benzylphosphonate (7) is described.Heterocyclization of RC(OMe):NCOEt (1a-d) with 2-mercaptoaniline (2) gave 2-R-benzothiazoles (3a-d; R = Ph, PhCH₂, 4-MeC₆H₄, 4-ClC₆H₄).Bromination of 3c (R = 4-MeC₆H₄) by NBS gave 2-(4-bromomethylphenyl)benzothiazole (6), which was converted to title compound 7 in 68% yield by Arbuzov reaction with tri-Et phosphite in xylene at reflux.The structure of these products were confirmed by means of IR,¹H,¹³C, and ³¹P NMR spectroscopy and mass spectra.

Four aryl vinyl diethyl benzylphosphonates related to Fostedil were synthesized and evaluated for their in vitro calcium-inhibitory activity. None of these compounds exhibited any calcium antagonistic profile. Unlike a series of diethyl-styryl benzylphosphonates, previously described, the presence of two aromatic rings linked by a vinyl group did not improve the calcium antagonistic activity.