Highly fluorinated analogues of pharmacologically active compounds

Abstract

The pentafluorophenyl analogues of noradrenaline, adrenaline, and N-methyladrenaline [C₆F₅·CH(OH)·CH₂·NR¹R² with R¹= R²= H; R¹= H, R²= Me; R¹= R²= Me, respectively] have been prepared by reduction with sodium borohydride of the corresponding amino-ketones obtained by standard methods. 3-(N-2-Chloroethyl-N-ethyl)-aminomethyl-4,5,6,7-tetrafluorobenzo[b]thiophen has also been synthesised as a potential catecholamine antagonist and anti-tumour agent, by a method involving the cyclisation with polyphosphoric acid of 2,3,4,5-tetra-fluorophenylthiopropanone to give the expected 4,5,6,7-tetrafluoro-3-methylbenzo[b]thiophen, and thence by standard methods. The above pentafluorophenyl compounds are only very weak catecholamine antagonists.