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Modification of the amino substituent gave the isomeric tetramethyl derivative 17 and the 4,7-dihydroindanyl indacaterol derivative 29 which had comparable decreases in affinity and selectivity when compared to 1. The 5-n-butylindanyl analogue 16, as a diasteroisomeric mixture epimeric at the 2-indanyl position, exhibited a similar binding profile to 1, suggesting the potential for a similar overall profile. However, the additional stereochemical complexity in 16 reduced the attractiveness of this analogue for further follow up studies. Introduction of the a-methyl group into the amino substituent gave the analogue 25 which led to the anticipated increase in b2adrenoceptor affinity, of greater than 10-fold relative to 1.However, this increase in affinity was also accompanied by an even greater relative increase in b1-adrenoceptor affinity and an overall reduction in binding selectivity.
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»¯ºÏÎï17¡¢29µÄ  Modification of the amino substituent gave the isomeric tetramethyl derivative 17 and the 4,7-dihydroindanyl indacaterol derivative 29 which had comparable decreases in affinity and selectivity when compared to 1.
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5Â¥: Originally posted by jiangsishui at 2012-10-24 09:07:50

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