Thienopyrimidines as b3-adrenoceptor agonists: Hit-to-lead optimization

Thienopyrimidines as b3-adrenoceptor agonists: Hit-to-lead optimization

Resulting from a vHTS based on a pharmacophore alignment on known b3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human b3-AR agonist, yielding a lead compound with an excellent cellular activity of EC sub(50) = 20 pM, selecti...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2010-10, Vol.20 (20), p.6108-6115
Hauptverfasser: Tasler, Stefan, Baumgartner, Roland, Ammendola, Astrid, Schachtner, Josef, Wieber, Tanja, Blisse, Marcus, Rath, Sandra, Zaja, Mirko, Klahn, Philipp, Quotschalla, Udo, Ney, Peter
Format: Artikel
Sprache:eng
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pharmacophores
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Zusammenfassung:Resulting from a vHTS based on a pharmacophore alignment on known b3-adrenoceptor ligands, an aryloxypropanolamine scaffold comprising a thienopyrimidine moiety was further optimized as a human b3-AR agonist, yielding a lead compound with an excellent cellular activity of EC sub(50) = 20 pM, selectivity over hb1- and hb2-adrenoceptors and a promising safety profile.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2010.08.039