Thienopyrimidines as β3-adrenoceptor agonists: Hit-to-lead optimization
| Autor: | Peter Ney, Marcus Blisse, Philipp Klahn, Udo Quotschalla, Roland Baumgartner, Josef Schachtner, Tanja Wieber, Mirko Zaja, Astrid Ammendola, Sandra Rath, Stefan Tasler |
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| Rok vydání: | 2010 |
| Předmět: |
Agonist
Molecular model Cell Survival medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Biochemistry Chemical synthesis Cell Line chemistry.chemical_compound Drug Discovery medicine Humans Moiety Molecular Biology Chemistry Organic Chemistry Hit to lead Pyrimidines Drug Design Receptors Adrenergic beta-3 Molecular Medicine Adrenergic beta-3 Receptor Antagonists Pharmacophore Selectivity Lead compound Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 20:6108-6115 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2010.08.039 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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