Phosphonyl ester conjugates as prodrugs

A prodrug compound

• where R8 in each occurrence is OH, OR9,
• Q is O or S;
• R3 is —(CH2)n—, —CHCH3(CH2)n—, or —(C6H4)(CH2)n;
• n is independently in each occurrence an integer between 0 and 12;
• R10 is independently in each occurrence H, F, Cl, Br, C1-C4 alkyl, C0-C4 primary amine, C0-C4 amine having one or two C1-C8 alkyl substituents, C0-C4 hydroxyl, C0-C4 carboxyl, C0-C4 sulfonate, and a quaternary amine or
• R5 is H, or
• R6 is an amino acid side chain of —H, —NH2, —C1-5 alkyl, —C1-5 alkanol, —C1-5 alkyl carboxylic acid, —C1-5 alkyl amine, —C1-5 alkyl amide, —C1-5 alkyl imine, —C1-5 alkyl delta-guanido and -methylphenyl;
• and R5 is isopropyl, isobutyl, tert-butyl, or isopentyl or 2-tert-pentyl;
• C* is either a R- or S-chiral carbon atom;
• and L is a nullity or a linker a group of C1-C8 alkyl, C1-C8 alkyl having a pendent heteroatom containing moiety of O, N or S present as a carboxyl, carbonyl, hydroxyl, amino, amido, sulfonyl, or quaternary amino;
• and R7 is a C1-C5 alkyl, —(CH2)n—C6R58, —(CH2)n—CH—(C6R58)2, —(CH2)nC(C6R58)3, or —C5N′R58.

An inventive prodrug compound of the formula:

• where R3 is —(CH2)n—, —CHCH3(CH2)n, and
• —(C6H4)(CH2)n;
• R4 is O-isopropyl, O-isobutyl, O-tert-butyl or O-2-tert-pentyl,
• —O—(CH2)n—C6R510, —O—(CH2)n—CH—(C6R510)2, —O—(CH2)nC(C6R510)3, and —O—C5N′R510;
• n is independently in each occurrence an integer between 0 and 12;
• R10 is independently in each occurrence H, F, Cl, Br, C1-C4 alkyl, C0-C4 primary amine, C0-C4 amine having one or two C1-C8 alkyl substituents, C0-C4 hydroxyl, C0-C4 carboxyl, C0-C4 sulfonate, and a quaternary amine or
• R5 is H, or
• R6 is an amino acid side chain of —H, —NH2, —C1-5 alkyl, —C1-5 alkanol, —C1-5 alkyl carboxylic acid, —C1-5 alkyl amine, —C1-5 alkyl amide, —C1-5 alkyl imine, —C1-5 alkyl delta-guanido and -methylphenyl;
• and R7 is —O-isopropyl, —O-isobutyl, —O-tert-butyl, —O-isopentyl or —O-2-tert-pentyl;
• and C* is either a R- or S-chiral carbon atom. L is a nullity or a linker a group of C1-C8 alkyl, C1-C8 alkyl having a pendent heteroatom containing moiety of O, N or S present as a carboxyl, carbonyl, hydroxyl, amino, amido, sulfonyl, or quaternary amino. It is appreciated that a radioisotope or spectroscopically active label is readily added as a pendent moiety to the linker L.