Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2012 Oct 1;22(19):6280-5. doi: 10.1016/j.bmcl.2012.07.096. Epub 2012 Aug 4.

An investigation into the structure-activity relationships associated with the systematic modification of the β(2)-adrenoceptor agonist indacaterol.

Author information

1
Novartis Institutes for BioMedical Research, Respiratory Diseases Area, Horsham, United Kingdom.

Abstract

The synthesis of a series of indacaterol analogues in which each of the three structural regions of indacaterol are modified in a systematic manner is described. Evaluation of the affinity of these analogues for the β(2)-adrenoceptor identified the 3,4-dihydroquinolinone and 5-n-butylindanyl analogues to demonstrate the most similar profiles to indacaterol. An α-methyl aminoindane analogue was discovered to be 25-fold more potent than indacaterol, and functional studies revealed an atypical β(2)-adrenoceptor activation profile for this compound consistent with that of a slowly dissociating 'super agonist'.

PMID:
22932315
DOI:
10.1016/j.bmcl.2012.07.096
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center