Stanford Research Institute

Sri International

Priscilla A Sturm

David W Henry

Elmer J Reist

Certain open chain purine nucleoside phosphonate derivatives have antiviral activity against the Herpes group of viruses, and also show effective antiviral activity against retroviruses, including human immunodeficiency virus (HIV). These compounds have the formula ##STR1## wherein B represents a substituted or unsubstituted purine base, especially adenine or guanine and their halogenated derivatives. R1 is selected from H, methyl, hydroxymethyl, halomethyl, azidomethyl, and cyano; R2 is selected from H, methyl, hydroxymethyl, halomethyl, azidomethyl, cyano, and OH; also when R2 is OH the carbon to which it is attached may be oxidized so that the H there shown and R2 together may be =0; and n is an integer of 0-5. The compounds of the invention further include the pharmaceutically acceptable mono and dibasic salts and the mono- and diesters of the phosphonate moiety and the acid addition salts of the murine-substituted purines. In addition, when R1 or R2 is --CH.sub.2 OH, or when R2 is OH, the acyl (1-6C) esters of these alcohols are included in the invention. Further, when n is 0, 1, or 2 and R1 is CH.sub.2 OH, the compounds of Formula 1 include the cyclic forms wherein formal dehydration between R1 and one of the --OH groups on the phosphonate results in compounds of the formula: ##STR2## and their corresponding salts and esters.

Acyclic purine phosphonate nucleotide analogs

The compounds 3-(N-diethylcarbamyl)amino-1-methyl pyrrolidine, 3-(N-carbethoxy-N-methyl)amino-1-methyl pyrrolidine, 1-diethylcarbamyl-3-(N-methyl)amino pyrrolidine and 1-diethylcarbamyl-3-dimethylamino pyrrolidine, said compounds having utility as antifilarial agents.

N-substituted 3-aminopyrrolidines

The compounds 4-carbethoxy-1,4-diazabicyclo[3.2.1]octane and 4-diethylcarbamyl-1,4-diazabicyclo[3.2.1]octane, said compounds having utility as antifilarial agents.

1,4-Diazabicyclo[3.2.1]octanes

Twelve analogs of diethylcarbamazine as prepared by acylation of 3- and 8-methyl-3,8-diazabicyclo[3.2.1]octane, 2-methyl-2,5-diazabicyclo[2.2.2]octane, and 2-methyl-2,5-diazabicyclo[2.2.1]heptane with diethylcarbamyl chloride, ethyl chloroformate, ethyl isocyanate, and cyclohexanecarbonyl chloride. These compounds are formally derived from diethylcarbamazine in possessing two- or one-carbon bridges over the piperazine ring. The compounds have utility as antifilarial agents and as bronchodilators.

3-Substituted-8-methyl-3,8-diazabicyclo[3.2.1]octanes

Twelve analogs of diethylcarbamazine as prepared by acylation of 3- and 8-methyl-3,8-diazabicyclo[3.2.1]octane, 2-methyl-2,5-diazabicyclo[2.2.2]octane, and 2-methyl-2,5-diazabicyclo [2.2.1]heptane with diethylcarbamyl chloride, ethyl chloroformate, ethyl isocyanate, and cyclohexanecarbonyl chloride. These compounds are formally derived from diethylcarbamazine in possessing two- or one-carbon bridges over the piperazine ring. The compounds have utility as antifilarial agents and as bronchodilators.

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Priscilla A Sturm