Back to results
US 6,140,310 AGranted
Phosphorous prodrugs
AssigneeDrug Innovation & Design, Inc.
InventorArnold Glazier
Life of this patent
Estimating the term…
Abstract
The composition and methods of synthesis of phosphorus prodrugs are described. These methods can be used to convert negatively charged phosphorus bearing drugs into neutrally charged; lipid soluble prodrugs which are able to passively diffuse into cells and into tissues in vivo. Prodrugs for a variety of antiviral and anti-leukemic agents are described.
Claims5
A prodrug compound for a parent drug, wherein the parent drug has the structure:
- ##STR31## wherein X is oxygen or sulfur;
- n is 1 or 2;
- and
- Y is defined by the remainder of the parent drug;
- such that the parent drug is not phosphoric acid;
- wherein the prodrug compound has the structure:
- ##STR32## wherein X, n and Y are defined above;
- and "A" is of the formula:
- ##STR33## wherein:
- R.sub.1, R.sub.3 and R.sub.6 are independently a (--O--CO--R8) group;
- a (--O--CO.sub.2 --R8) group;
- an N-substituted amino carbonyl oxy;
- a (--O--C(O)--NHCH.sub.3) group;
- a (--O--C(O)--N(CH.sub.3).sub.2) group;
- hydrogen;
- a halogen;
- a (--CO.sub.2 R9) group;
- a methyl group;
- a hydroxymethyl group(HO--CH.sub.2 --);
- a hydroxyethyl;
- a --CH.sub.2 --CO.sub.2 R.sub.11 group or a group which undergoes biotransformation in vivo to yield a hydroxy group;
- R.sub.2 and R.sub.7 are independently hydrogen;
- a (--CO.sub.2 --R10) group;
- a methyl group;
- a halogen;
- a methoxy group;
- (--O--CO--R8);
- or a hydroxymethyl group (HO--CH.sub.2);
- R.sub.4 and R.sub.5 are independently hydrogen;
- a methyl group;
- a methoxy-methyl (--CH.sub.2 --O--CH.sub.3);
- a (--CH.sub.2 --CO.sub.2 --R12) group;
- a (--CH.sub.2 --CO--CH.sub.3) group;
- a (--CH(CH.sub.3)--CO.sub.2 --R12) group;
- a (--CH.sub.2 --CO--NH.sub.2) group;
- a (--CH.sub.2 --NO.sub.2) group;
- or a (--CH.sub.2 --SO.sub.2 --CH.sub.3) group;
- R8 is an alkyl;
- a substituted or unsubstituted phenyl group, or wherein R8 can also be selected such that R8--CO.sub.2 H is an amino acid, lactic acid, glycolic acid, glyceric acid, or acetoacetic acid;
- R9, R10, R11 and R12, independently are methyl, ethyl, phenyl, or benzyl;
- and wherein at least one of the groups:
- R.sub.1, R.sub.3 or R.sub.6 is a (--O--CO--R8);
- a (--OCO.sub.2 R8) group;
- a (--O--CO--NHCH.sub.3) group;
- or a (--O--CO--N(CH.sub.3).sub.2) group;
- or a group which undergoes biotransformation in vivo to yield a hydroxy group.
43 more elements
A prodrug compound for a parent drug, wherein the parent drug has the structure:
- ##STR34## wherein X is oxygen or sulfur;
- n is 1 or 2;
- and
- Y is defined by the remainder of the parent drug, such that the parent drug is not phosphoric acid;
- wherein the prodrug compound has the structure:
- ##STR35## wherein X, n and Y are defined above;
- and "A" is of the formula:
- ##STR36## wherein R.sub.1 is a (--O--CO--R.sub.8) group;
- R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7 are each hydrogen;
- R.sub.5 is selected from the group consisting of hydrogen, a methyl group, a (--CH.sub.2 --O--CH.sub.3) group, a (--CH.sub.2 --CO.sub.2 --R.sub.12) group, a (--CH.sub.2 --CO--CH.sub.3) group, a (--CH(CH.sub.3)--CO.sub.2 --R.sub.12) group, a (--CH.sub.2 --CO--NH.sub.2) group, a (--CH.sub.2 --NO.sub.2) group, and a (--CH.sub.2 --SO.sub.2 --CH.sub.3) group;
- R.sub.8 is an alkyl, a substituted or unsubstituted phenyl group, or wherein R.sub.8 can also be selected such that R.sub.8 --CO.sub.2 H is an amino acid, lactic acid, glycolic acid, glyceric acid, or acetoacetic acid;
- and
- R.sub.12 is methyl, ethyl, phenyl, or benzyl.
10 more elements
Dependencies are inferred from the claim text.