IN-VIVO ANTIHERPESVIRUS ACTIVITY OF N-7-SUBSTITUTED ACYCLIC NUCLEOSIDE ANALOG 2-AMINO-7-[(1,3-DIHYDROXY-2-PROPOXY)METHYL] PURINE

The efficacy of 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S22 42) was evaluated in several animal models for herpesvirus infections. Compound S2242 was more effective than acyclovir (i) when administere d subcutaneously in a model for herpes simplex virus type 1 (HSV-1)-in duced mortality in immunocompetent mice and (ii) when applied topicall y to hairless (hr/hr) mice that had been infected intracutaneously wit h HSV-2. In SCID (severe combined immune deficient) mice that had been infected with a thymidine kinase-deficient HSV-1 strain, S2232 (admin istered subcutaneously at a dosage of 50 mg/kg/day) completely protect ed against virus-induced mortality whereas foscarnet was less effectiv e 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. Th e compound was more effective when a given dose was fractionated and a dministered 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 S2232 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 fo r 6 weeks). However, akin to ganciclovir, compound S2242 significantly reduced testicle weight, testicle morphology, and spermatogenesis.