Water soluble prodrugs of secondary and tertiary amine containing drugs and methods of making thereof

A composition containing an N-phosphoryloxymethyl prodrug of tertiary amine containing drugs having the following formula VI, ##STR29## wherein R.sub.1, R.sub.2 and R.sub.3 are substituents which comprise the parent tertiary amine, R.sub.4 and R.sub.5 are each hydrogen or an organic residue selected from the group consisting of a straight-chain, substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic group, and a substituted or unsubstituted cyclic group, R.sub.4 and R.sub.5 may contain one or more heteroatoms and may also be joined to form a ring, and X is an organic or inorganic cation, A represents an anion, and a pharmaceutically acceptable carrier thereof.

A method of making a soluble prodrug of a tertiary amine containing parent drug comprising derivatization of a prodrug moiety of formula VII ##STR30## wherein A represents a leaving group, R.sub.4 and R.sub.5 are each hydrogen or an organic residue selected from the group consisting of a straight-chain, substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic group, and a substituted or unsubstituted cyclic group, R.sub.4 and R.sub.5 may contain one or more heteroatoms and may also be joined to form a ring, and Y is a phosphate protecting group,

• through the nucleophilic attack of a tertiary amine causing the displacement of A, followed by the removal of the protecting groups.

A method of making a soluble prodrug of a tertiary amine containing parent drug comprising reaction of a compound of the following Formula VIII ##STR31## wherein R.sub.4 and R.sub.5 are each an organic or inorganic residue, and W and Z are leaving groups, with a tertiary amine to displace one of either W or Z and reacting the remaining leaving group with a protected phosphate.