ANTIRETROVIRAL ACTIVITIES OF ACYCLIC NUCLEOSIDE PHOSPHONATES [9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE, 9-(2-PHOSPHONYLMETHOXYETHYL) GUANINE, (R)-9-(2-PHOSPHONYLMETHOXYPROPYL)ADENINE, AND MDL-74,968] IN CELL-CULTURES AND MURINE SARCOMA VIRUS-INFECTED NEWBORN NMRI MICE

From a side-by-side comparative study, the acyclic nucleoside phosphon ates (R)-9-(2-phosphonylmethoxypropyl)adenine [(R)-PMPA] and 9-(2-meth ylidene-3-phosphonomethoxypropyl) guanine (MDL 74,968) proved more sel ective in their inhibitory effect on human immunodeficiency virus type s 1 and 2, feline immunodeficiency virus, and Moloney murine sarcoma v irus (MSV) in cell cultures than the 9-(2-phosphonylmethoxyethyl) deri vatives of adenine (PMEA) and guanine (PMEG). In particular, PMEG prov ed quite toxic. PMEA, (R)-PMPA, and MDL 74,968 afforded a marked delay in MSV-induced tumor initiation in MSV-infected newborn NMRI mice and substantially delayed associated animal death at doses as low as 4 to 10 mg/kg of body weight, Treatment of the NMRI mice with PMEA, (R)-PM PA, and MDL 74,968 at 25 or 50 mg/kg resulted in a high percentage of long-term survivors.