A multivalent approach to the discovery of long-acting β 2-adrenoceptor agonists for the treatment of asthma and COPD

JR Jacobsen, SK Choi, J Combs, EJL Fournier…

Index: Jacobsen, John R.; Choi, Seok Ki; Combs, Jesse; Fournier, Eric J.L.; Klein, Uwe; Pfeiffer, Juergen W.; Thomas, G. Roger; Yu, Cecile; Moran, Edmund J. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 2 p. 1213 - 1218

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Citation Number: 18

Abstract

A multivalent approach was applied to the design of long-acting inhaled β2-adrenoceptor agonists. A series of dimeric arylethanolamines based on the short acting β2-adrenoceptor agonist albuterol were prepared, varying the nature and length of the linker between the basic nitrogens. None of the C2-symmetric dimers demonstrated increased potency, however dimer 5j, derived from 4-phenethylamine, was found to have increased binding ...