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

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

  • Bioorg Med Chem Lett. 2012 Oct 1;22(19):6280-5. doi: 10.1016/j.bmcl.2012.07.096.
David Beattie 1,  David Beer,  Michelle E Bradley,  Ian Bruce,  Steven J Charlton,  Bernard M Cuenoud,  Robin A Fairhurst,  David Farr,  John R Fozard,  Diana Janus,  Elizabeth M Rosethorne,  David A Sandham,  David A Sykes,  Alexandre Trifilieff,  Katharine L Turner,  Elke Wissler
Affiliations

Affiliation

  • 1 Novartis Institutes for BioMedical Research, Respiratory Diseases Area, Horsham, United Kingdom.
PMID: 22932315 DOI: 10.1016/j.bmcl.2012.07.096
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'.

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