Synthesis, β-adrenergic blocking activity and β-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates

The compounds 1-isopropylamino-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalate (5) and 1-tert-butylamino-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalate (6) were synthesized from thymol (1), a naturally occurring agent in Thymus vulgaris L. Pharmacological evaluation of 5 and 6 were carried out using mouse ECG and isolated rat uterus models. Pretreatment of 5 (100 μg/kg, i.v.) and 6 (50 μg/kg, i.v.) antagonized isoprenaline (2 μg/kg, i.v.) induced tachycardia, similar to that of atenolol (CAS 29122-68-7, 20 μg/kg, i.v.) pretreatment in mouse ECG experiments as measured by R-R interval. Pretreatment of 5 and 6 blocked isoprenaline and adrenaline induced relaxation of isolated rat uterus (unprimed). Also the compounds 5 and 6 were subjected to in vitro β₁- and β₂-adrenergic receptor binding assay using turkey erythrocyte membrane (β₁) and lung homogenate of rats (β₂). Both 5 and 6 showed β-adrenergic receptor affinity comparable with that of propranolol (propranolol hydrochloride, CAS 318-98-9) with out selectivity to any one β-adrenergic receptor. These results suggest that both the compounds possess non-selective β-adrenergic blocking activity, with the tert-butyl derivative 6 being more active than the isopropyl derivative 5.