{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bai B"],"funding":["Li Ka Shing Applied Virology Institute"],"pagination":["e202400629"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11911297"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(6)"],"pubmed_abstract":["The development of non-nucleoside inhibitors targeting human cytomegalovirus (HCMV) polymerase presents a promising approach for enhancing therapeutic treatment for patients with sustained HCMV viremia. A series of non-nucleoside HCMV DNA polymerase inhibitors with various substitution groups at 2-postition of the novel pyrido[2,3-b]pyrazine core was synthesized and investigated. The study focused on optimizing HCMV polymerase inhibition while minimizing off-target inhibition of human ether-à-go-go (hERG) ion channel. Several compounds exhibited strong antiviral activity against HCMV (typical EC<sub>50</sub><1 μM), with favorable cytotoxicity profiles. A potent lead compound, 27, with an EC<sub>50</sub> of 0.33 μM and improved aqueous solubility was identified. Further antiviral assessment"],"journal":["ChemMedChem"],"pubmed_title":["Discovery of Novel Pyrido[2,3-b]Pyrazine Human Cytomegalovirus Polymerase Inhibitors with Broad Spectrum Antiherpetic Activity and Reduced hERG Inhibition."],"pmcid":["PMC11911297"],"funding_grant_id":["RES0055738"],"pubmed_authors":["Srinivas Kandadai A","Hena M","Bai B","Shen J","Nieman JA","Belovodskiy A","Houghton M"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of Novel Pyrido[2,3-b]Pyrazine Human Cytomegalovirus Polymerase Inhibitors with Broad Spectrum Antiherpetic Activity and Reduced hERG Inhibition.","description":"The development of non-nucleoside inhibitors targeting human cytomegalovirus (HCMV) polymerase presents a promising approach for enhancing therapeutic treatment for patients with sustained HCMV viremia. A series of non-nucleoside HCMV DNA polymerase inhibitors with various substitution groups at 2-postition of the novel pyrido[2,3-b]pyrazine core was synthesized and investigated. The study focused on optimizing HCMV polymerase inhibition while minimizing off-target inhibition of human ether-à-go-go (hERG) ion channel. Several compounds exhibited strong antiviral activity against HCMV (typical EC<sub>50</sub><1 μM), with favorable cytotoxicity profiles. A potent lead compound, 27, with an EC<sub>50</sub> of 0.33 μM and improved aqueous solubility was identified. Further antiviral assessment","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2025-04-26T08:44:20.261Z","creation":"2025-04-06T12:48:04.629Z"},"accession":"S-EPMC11911297","cross_references":{"pubmed":["39656778"],"doi":["10.1002/cmdc.202400629"]}}