Synthesis and β-adrenoceptor agonist properties of (±)-1-(3',4'- dihydroxyphenoxy)-3-(3',4'-dimethoxyphenyl) ethylamino-2-propanol hydrochloride, (±)-RO363.HCl, and the (2S)-(-)-isomer

Article abstract of DOI:10.1016/S0223-5234(99)80103-2

The synthesis of (±)-1-(3',4'-dihydroxyphenoxy)-3-(3',4'- dimethoxyphenyl)ethylamino-2-propanol hydrochloride, (±)RO363.HCl, and the (2S)-(-)-isomer is described for the first time. The binding affinities for (±)-RO363.HCl, (2S)-(-)-RO363.HCl and a number of well known β-adrenoceptor agonists for transfected humanβ₁,-, β₂- and β₃-adrenoceptors expressed in Chinese hamster ovary cells have been determined and compared with the functional potencies in rat atria (β₁) and trachea (β₂). The results indicate that both (±)-RO363 and (2S)-(-)-RO363 are selective for the human and rat β₁-adrenoceptors. The (2S)-(-)-isomer of RO363, as expected, has a higher binding affinity for the human and functional potency for rat β- adrenoceptor subtypes than the racemate. However, in contrast to the catecholamines and formoterol, the functional potency of the racemic mixture and its (-)-enantiomer are not significantly different from their binding affinity, suggesting that they are examples of partial agonists with sufficient intrinsic activity to produce full agonist responses.