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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 human β 1 -, β 2 - and β 3 -adrenoceptors expressed in Chinese hamster ovary cells have been determined and compared with the functional potencies in rat atria (β 1 ) and trachea (β 2 ). The results indicate that both (±)-RO363 and ( 2S )-(-)-RO363 are selective for the human and rat β 1 -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. |
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