title: Thienopyrimidines as β3-adrenoceptor agonists: hit-to-lead optimization.
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 EC(50)=20 pM, selectivity over hβ1- and hβ2-adrenoceptors and a promising safety profile.
authors.affiliation: 4SC AG, Am Klopferspitz 19a, 82152 Planegg-Martinsried, Germany. stefan.tasler@4sc.com
authors.forename: Stefan
authors.initials: S
authors.lastname: Tasler
authors.forename: Roland
authors.initials: R
authors.lastname: Baumgartner
authors.forename: Astrid
authors.initials: A
authors.lastname: Ammendola
authors.forename: Josef
authors.initials: J
authors.lastname: Schachtner
authors.forename: Tanja
authors.initials: T
authors.lastname: Wieber
authors.forename: Marcus
authors.initials: M
authors.lastname: Blisse
authors.forename: Sandra
authors.initials: S
authors.lastname: Rath
authors.forename: Mirko
authors.initials: M
authors.lastname: Zaja
authors.forename: Philipp
authors.initials: P
authors.lastname: Klahn
authors.forename: Udo
authors.initials: U
authors.lastname: Quotschalla
authors.forename: Peter
authors.initials: P
authors.lastname: Ney
mesh_terms: D058673:Adrenergic beta-3 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D015195:Drug Design; D006801:Humans; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*
chemical_list: D058673:Adrenergic beta-3 Receptor Antagonists; D011743:Pyrimidines; D022702:Receptors, Adrenergic, beta-3; C476003:thienopyrimidine