Gudmundsson Kristjan S, Johns Brian A, Wang Zhicheng, Turner Elizabeth M, Allen Scott H, Freeman George A, Boyd F Leslie, Sexton Connie J, Selleseth Dean W, Moniri Kelly R, Creech Katrina L
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA.
Bioorg Med Chem. 2005 Sep 15;13(18):5346-61. doi: 10.1016/j.bmc.2005.05.043.
Herpesviruses are a significant source of human disease; amongst these herpes simplex virus 1 (HSV-1) and HSV-2 are very prevalent and cause recurrent infections. We recently identified a pyrazolo[1,5-a]pyridine scaffold that showed promising activity against HSV-1 and HSV-2 in Vero cell antiviral assays. Here, we describe the synthesis and anti-herpetic activity of several 3-pyrimidinyl-2-phenylpyrazolo[1,5-a]pyridines with differing 2-phenyl substitution patterns. Approaches to rapidly access a number of analogs with different 2-phenyl substitution patterns are outlined. Several of the compounds described have comparable activity to acyclovir against HSV-1 and HSV-2.
疱疹病毒是人类疾病的一个重要来源；在这些病毒中，单纯疱疹病毒1型（HSV-1）和HSV-2非常普遍，并会引起复发性感染。我们最近鉴定出一种吡唑并[1,5-a]吡啶支架，在Vero细胞抗病毒试验中显示出对HSV-1和HSV-2有良好的活性。在此，我们描述了几种具有不同2-苯基取代模式的3-嘧啶基-2-苯基吡唑并[1,5-a]吡啶的合成及其抗疱疹活性。概述了快速获得多种具有不同2-苯基取代模式类似物的方法。所描述的几种化合物对HSV-1和HSV-2的活性与阿昔洛韦相当。
