title: Identification of novel allosteric modulators for the G-protein coupled US28 receptor of human cytomegalovirus.
abstract: The highly constitutively active G-protein coupled receptor US28 of human cytomegalovirus (HCMV) is an interesting pharmacological target because of its implication on viral dissemination, cardiovascular diseases and tumorigenesis. We found that dihydroisoquinolinone and tetrahydroisoquinoline scaffolds may be promising lead structures for novel US28 allosteric inverse agonists. These scaffolds were rapidly synthesized by radical carboamination reactions followed by non-radical transformations. Our novel US28 allosteric modulators provide valuable scaffolds for further ligand optimization and may be helpful chemical tools to investigate molecular mechanisms of US28 constitutive signaling and its role in pathogenesis.
authors.affiliation: Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schuhstraße 19, D-91052 Erlangen, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Kralj
authors.forename: Alexander
authors.initials: A
authors.lastname: Wetzel
authors.forename: Shohreh
authors.initials: S
authors.lastname: Mahmoudian
authors.forename: Thomas
authors.initials: T
authors.lastname: Stamminger
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; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D019707:Receptors, Chemokine / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000819:agonists*
chemical_list: D007546:Isoquinolines; D019707:Receptors, Chemokine; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins