Thienopyrimidines as β3-adrenoceptor agonists: hit-to-lead optimization.

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.