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

• Tác giả: Bing Bai, Alexandr Belovodskiy, Mostofa Hena, Michael Houghton, James A Nieman, John Shen, Appan Srinivas Kandadai
• Ngôn ngữ: eng
• Thông tin xuất bản: Germany : ChemMedChem , 2025
• Bộ sưu tập: NCBI
• ID: 716141

Tóm tắt

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