A novel series of 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamides have been identified as potential antivirals against human herpesvirus infections resulting from human cytomegalovirus (HCMV), herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV). Compounds 10c and 14 demonstrated broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, and VZV. High specificity for the viral polymerases was observed compared to human alpha polymerase. The antiviral activity of 10c and 14, as determined by plaque reduction assay, was comparable or superior to that of existing antiherpes drugs, ganciclovir (for HCMV) and acyclovir (for HSV-1 and VZV). Drug resistance to compound 14 correlated to point mutations in conserved domain III of the herpesvirus DNA polymerase, but these mutations do not confer resistance to existing nucleoside therapy. In addition, compound 14 maintained potent antiviral activity against acyclovir-resistant HSV-1 strains. Substitution to the pyridone nitrogen (N7) was found to be critical for enhanced in vitro antiviral activity.

中文翻译：

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4-Oxo-4,7-dihydrothieno [2,3-b]吡啶类是人类巨细胞病毒和相关疱疹病毒聚合酶的非核苷抑制剂。

一种新型的4-氧代-4,7-二氢噻吩并[2,3-b]吡啶-5-甲酰胺被鉴定为潜在的抗人疱疹病毒感染的抗病毒药，人疱疹病毒是由人巨细胞病毒（HCMV），1型单纯疱疹病毒（HSV）引起的。 -1）和水痘带状疱疹病毒（VZV）。化合物10c和14对疱疹病毒聚合酶HCMV，HSV-1和VZV表现出广谱抑制作用。与人α聚合酶相比，观察到对病毒聚合酶的高特异性。通过噬菌斑减少测定法确定的10c和14的抗病毒活性与现有抗疱疹药物更昔洛韦（对于HCMV）和阿昔洛韦（对于HSV-1和VZV）相当或更好。对化合物14的耐药性与疱疹病毒DNA聚合酶保守结构域III中的点突变有关，但是这些突变不会赋予对现有核苷治疗的抗性。另外，化合物14保持了对抗阿昔洛韦的HSV-1菌株的有效抗病毒活性。发现取代吡啶酮氮（N7）对于增强体外抗病毒活性至关重要。