Activation by thymidine kinase and potent antiherpetic activity of 2′-nor-2′-deoxyguanosine (2′NDG)

摘要: Summary In an investigation of the substrate specificity herpes simplex type I (HSV-1) thymidine kinase, certain chemical analogs acyclovir were prepared. One these, 9-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl]guanine (2′-nor-2′-deoxyguanosine, 2′NDG), prepared in a five-step convergent synthesis from glycerol formal and guanine, was more efficient for kinase GMP rapidly converted to corresponding triphosphate derivative virus-infected cells than known antiherpetic agent, acyclovir. 2′NDG showed activity cell culture (HSV-1 HSV-2 primary rabbit kidney cells) equivalent vivo comparison with five other agents including protection mice against HSV-1 induced encephalitis, at least 60-fold effective. There no effect on viability depression weight gain or evidence toxicity which could be attributed treatment 2′NDG.