The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist PMID: 25065493

ADC Targets in Oncology

2026-04-10

The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist

Bioorg Med Chem Lett. 2014 Sep 1;24(17):4341-7. doi: 10.1016/j.bmcl.2014.06.014.

Nicola Arnold ¹ , David Beattie ¹ , Michelle Bradley ¹ , Andrew Brearley ¹ , Lyndon Brown ¹ , Steven J Charlton ¹ , Robin A Fairhurst ² , David Farr ¹ , John Fozard ¹ , Joe Fullerton ¹ , Martin Gosling ¹ , Julia Hatto ¹ , Diana Janus ¹ , Darryl Jones ¹ , Lynne Jordan ¹ , Christine Lewis ¹ , Janet Maas ¹ , Clive McCarthy ¹ , Mark Mercer ¹ , Helen Oakman ¹ , Neil Press ¹ , Rachel Profit ¹ , Friedrich Schuerch ¹ , David Sykes ¹ , Roger J Taylor ¹ , Alexandre Trifilieff ¹ , Andrew Tuffnell ¹

Affiliations

Abstract

The optimisation of two series of 4-hydroxybenzothiazolone derived β2-adrenoceptor agonists, bearing α-substituted cyclopentyl and β-phenethyl amino-substituents, as inhaled long-acting bronchodilators is described. Analogues were selected for synthesis using a lipophilicity based hypothesis to achieve the targeted rapid onset of action in combination with a long duration of action. The profiling of the two series led to identification of the α-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting β2-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the backup development candidate to indacaterol from the Novartis LABA project.

Keywords

Bronchodilator; Chronic obstructive pulmonary disease; β(2)-Adrenoceptor agonist.