Prodrugs of phosphonates
AssigneesInstitute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, Rega Stichting v.z.w.
InventorsJohn E. Starrett, Jr., Muzammil M. Mansuri, John C. Martin, David R. Tortolani, Joanne J. Bronson
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Abstract
There are disclosed novel oral prodrugs of phosphonate nucleotide analogs which are hydrolyzable under physiological conditions to yield compounds which are useful as antiviral agents, especially as agents effective against RNA and DNA viruses. They may also find use as antitumor agents.
Claims18
Antivirally active compounds or intermediates therefor of the formula I or V ##STR25## wherein B represents adenyl (A), guanyl (G), or 2,6-diaminopurinyl (DAP);
- R.sup.1 and R.sup.2 are independently each OR.sup.4
- R.sup.3 represents ##STR26## X represents hydrogen, methyl or hydroxymethyl;
- R.sup.4 represents a physiologically hydrolyzable group selected from the group consisting of CH.sub.2 OC(O)R.sup.5 and CH(R.sup.5)OC(O)R.sup.5 (R, S, or RS stereochemistry);
- and
- R.sup.5 represents C.sub.1 -C.sub.20 alkyl, aryl or aryl-alkyl which may be substituted or unsubstituted by hydroxy or halogen.
Antivirally active compounds or intermediates therefor of Formula III ##STR27## wherein B represents adenyl (A), guanyl (G), or diaminopurinyl (DAP);
- R.sup.7 is OH;
- X represents hydrogen, methyl or hydroxymethyl;
- R.sup.1 is OR.sup.4 ;
- R.sup.4 represents a physiologically hydrolyzable group selected from the group consisting of CH.sub.2 OC(O)R.sup.5 and CH(R.sup.5)OC(O)R.sup.5 (R, S, or RS stereochemistry);
- and
- R.sup.5 represents C.sub.1 -C.sub.20 alkyl, aryl or aryl-alkyl which may be substituted or unsubstituted by hydroxy or halogen.
A method for the treatment of HSV-2, HCMV or HIV in a mammal which comprises orally administering to the mammal an antiviral effective non-toxic dose of 9-(2-phosphonylmethoxy) ethyladenine di(pivaloyloxymethyl)ester for a treatment period of sufficient duration to mitigate said infection.
Dependencies are inferred from the claim text.