In vivo antiherpesvirus activity of N-7-substituted acyclic nucleoside analog 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine.

Abstract	The efficacy of 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S2242) was evaluated in several animal models for herpesvirus infections. Compound S2242 was more effective than acyclovir (i) when administered subcutaneously in a model for herpes simplex virus type 1 (HSV-1)-induced mortality in immunocompetent mice and (ii) when applied topically to hairless (hr/hr) mice that had been infected intracutaneously with HSV-2. In SCID (severe combined immune deficient) mice that had been infected with a thymidine kinase-deficient HSV-1 strain, S2242 (administered subcutaneously at a dosage of 50 mg/kg/day) completely protected against virus-induced mortality whereas foscarnet was less effective and acyclovir had no or little protective effect. Compound S2242 was far more effective than ganciclovir in preventing or delaying murine cytomegalovirus-induced mortality in immunocompetent and SCID mice. The compound was more effective when a given dose was fractionated and administered on subsequent days than when this dose was administered in one single injection. A 5-day treatment course with S2242 (10 and 50 mg/kg/day) for newborn mice that had been infected with a lethal dose of murine cytomegalovirus suppressed virus-induced mortality. Compound S2242 had no inhibitory effect on the growth of weanling (at 50 mg/kg for 5 days) and 3- to 4-week-old mice (at doses of 50 to 200 mg/kg for 6 weeks). However, akin to ganciclovir, compound S2242 significantly reduced testicle weight, testicle morphology, and spermatogenesis.
Authors	J Neyts, G Jähne, G Andrei, R Snoeck, I Winkler, E De Clercq
Journal	Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 39 Issue 1 Pg. 56-60 (Jan 1995) ISSN: 0066-4804 [Print] United States
PMID	7695329 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antiviral Agents Purines S 2242 Ganciclovir Acyclovir
Topics	Acyclovir (therapeutic use) Animals Antiviral Agents (therapeutic use) Drug Evaluation, Preclinical Ganciclovir (therapeutic use) Herpesviridae Infections (drug therapy) Male Mice Mice, Hairless Mice, Nude Mice, SCID Models, Biological Purines (therapeutic use)

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