title: Synthesis and biological evaluation of biphenyl amides that modulate the US28 receptor.
abstract: To prepare and biologically evaluate 38 new potential US28 allosteric modulators, we employed a straightforward synthetic route involving radical arylation. The study was based on a former lead structure but with the dihydroisoquinolinone moiety replaced by substituted biphenyls. The investigation of structure-activity relationships among the new biphenyl-derived ligands led to a preliminary pharmacophore model and the discovery of four promising candidates with full inverse agonist properties.
authors.affiliation: Department Chemie und Pharmazie, Pharmazeutische Chemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, 91052 Erlangen (Germany).
authors.forename: Ana
authors.initials: A
authors.lastname: Kralj
authors.forename: Elif
authors.initials: E
authors.lastname: Kurt
authors.forename: Nuska
authors.initials: N
authors.lastname: Tschammer
authors.forename: Markus R
authors.initials: MR
authors.lastname: Heinrich
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000577:Amides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D003587:Cytomegalovirus / Q000378:metabolism; D015195:Drug Design; D054314:Drug Inverse Agonism; D057809:HEK293 Cells; D006801:Humans; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D000998:Antiviral Agents; D001713:Biphenyl Compounds; D019707:Receptors, Chemokine; D014764:Viral Proteins; C411191:US28 receptor, Cytomegalovirus; C010574:biphenyl
keywords: US28 receptor; amides; biphenyls; human cytomegalovirus; inverse agonism