Thienopyrimidines as β3-adrenoceptor agonists: Hit-to-lead optimization

…, R Baumgartner, A Ammendola, J Schachtner…

Index: Tasler, Stefan; Baumgartner, Roland; Ammendola, Astrid; Schachtner, Josef; Wieber, Tanja; Blisse, Marcus; Rath, Sandra; Zaja, Mirko; Klahn, Philipp; Quotschalla, Udo; Ney, Peter Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 20 p. 6108 - 6115

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Citation Number: 4

Abstract

Resulting from a vHTS based on a pharmacophore alignment on known β3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human β3-AR agonist, yielding a lead compound with an excellent cellular activity of EC50= 20pM, selectivity over hβ1-and hβ2-adrenoceptors and a promising safety profile.