New diastereomeric propranolol analogues - e.g. 1-(1-naphthyl:oxy)-3 -(1-phenyl:ethylamino) -propan-2-ol cpd., used to regulate blood pressure without affecting heart rate

摘要

Diastereomeric 1-(1-naphthyloxy)-3-(1-phenylethylamino)-propan-2-ols (I) are new. USE/ADVANTAGE - Cpds. (I) lower diastolic and systolic blood pressure, but do not affect heart rate. (SS)- and (RS)-cpds. (I) lowered blood pressure in rats in lower doses than (S)-(-)-propanolol. In an example (i) 1-naphthol (10.6 g) in DMF (74.5 ml) was treated with NaOH (2.7 g) in DMF (74.5 ml) and (R)-(-)-epichlorohydrin (5.9 ml) in DMF (37.5 ml) were added. The mixt. was stirred, treated with satd. NH4Cl soln. and water and extracted. Washing, drying and evapn. gave (R)-(-)-1-(naphthyloxy)-2,3-epoxypropane (II) (12.3 g; oil). (ii) (II) (12.3 g) and (S)-(-)-1-phenylethylamine (58 ml) were refluxed for 5 hrs. Vacuum removal of excess amine, dissolution in isopropanol and neutralisation with HCl/isopropanol gave (SS)-(-)-1-(1-naphthyloxy)- 3-(1-phenylethylamino)-propan-2-ol HCl (I); m.pt. 155-178 deg.C.