Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595350 | Bioorganic & Medicinal Chemistry Letters | 2012 | 6 Pages |
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 potency in vitro relative to the parent monomer. Optimization of this structure led to the identification of 22 (milveterol) which demonstrates high potency in vitro and long duration of action in a guinea pig model of bronchoprotection.
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Authors
John R. Jacobsen, Seok Ki Choi, Jesse Combs, Eric J.L. Fournier, Uwe Klein, Juergen W. Pfeiffer, G. Roger Thomas, Cecile Yu, Edmund J. Moran,