Discovery of Novel Pyrido[2,3-b]Pyrazine Human Cytomegalovirus Polymerase Inhibitors with Broad Spectrum Antiherpetic Activity and Reduced hERG Inhibition.

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 EC₅₀<1 μM), with favorable cytotoxicity profiles. A potent lead compound, 27, with an EC₅₀ of 0.33 μM and improved aqueous solubility was identified. Further antiviral assessment

SUBMITTER: Bai B 

PROVIDER: S-EPMC11911297 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature