Efficacy of 2'-nor-2'-deoxyguanosine treatment for orofacial herpes simplex virus type 1 skin infections in mice

Abstract

2'-Nor-2'-deoxyguanosine (2'NDG), a new antiviral agent, conferred protection when given orally or topically to hairless mice after the mice were subjected to orofacial infection with herpes simplex virus type 1. The average severity of orofacial lesions was significantly reduced in mice receiving oral gavage treatments twice daily for 7 days beginning 3 h postinfection. The minimum effective dose of 2'NDG was 0.2 mg/kg per day. A minimum of eight treatments over 4 days resulted in a significant reduction in lesion severity. Topical treatment begun 3 h postinfection and continued four times daily for 3 days resulted in a minimum effective dose of 0.06%. Oral treatment with 2'NDG begun as late as 72 h postinfection or topical treatment begun as late as 48 h postinfection resulted in significantly reduced lesion severity compared with lesion severity among placebo-treated animals. In addition, significant prevention of ganglionic infection occurred when 2'NDG was administered either orally or topically within 24 h after infection.

Synthesis and antiherpetic activity of (S)-, (R)-, and (.+-.)-9-[(2,3-dihydroxy-1-propoxy)methyl]guanine, linear isomers of 2'-nor-2'-deoxyguanosine

“…Two recrystallizations from hexane-CH2C12 yielded 9.08 g (71%) of off-white crystals: mp 83.5-84.5 °C;• [a]20!, +8.8°( c 2.5, CHC13) [lit.13 mp 84-84.5 °C; [a]D + 9.2°( c 1, CHC13)]; 200-MHz NMR (CDC13) 3.29 (d, J = 5 Hz, 2 H, CHCH2OTr), 3.67 (m, 2 H, CHCH2OCH2Ar), 3.78 (m, 1 H, CH2CHCH2), 4.53, 4.69 (s, each 2 H, OCH2Ar), 7. 25-7.5 (m, 25 H, ArH).…”

“…2.3-Di-O -benzyl-1-O -trityl-L-glycerol (25). Alkylation of 24 under the conditions used for the preparation of 22 yielded, after recrystallization from EtOH-CHCl3,29% of white crystals: mp 80-81 °C; [a]24D -9.4°(c 2.5, CHC13) [lit.18 mp 84.5-86 °C;…”

“…Lesion severity was evaluated on a graded scale of 0, for no evidence of infection, to 4.0, for total lesion involvement of the orofacial area. 25 Orofacial lesion scores were compared for different treatment groups by Duncan analysis27 in which pairwise comparisons were performed at a level of significance based on a 95% confidence interval.…”

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Ethyl l-Acetoxy-2,3-dihydro-7-methoxy-8-nitro-1Hpyrrolo[l,2-a ]indole-9-carboxylate (25). A mixture of 21 (646 mg, 2.5 mmol), freshly prepared lead tetraacetate (2.43 g, 4.4 mmol),20 and acetic acid (60 mL) was stirred under N2 for 10 h. Water was added and the mixture was filtered and extracted with ether.

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