Salts of isophosphoramide mustard and analogs thereof as anti-tumor agents
AssigneeDekk-Tec, Inc.
InventorLee Roy Morgan
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Abstract
The present disclosure relates to salts and compositions of isophosphoramide mustard and isophosphoramide mustard analogs. In one embodiment the salts can be represented by the formula wherein A+ represents an ammonium species selected from the protonated (conjugate acid) or quaternary forms of aliphatic amines and aromatic amines, including basic amino acids, heterocyclic amines, substituted and unsubstituted pyridines, guanidines and amidines; and X and Y independently represent leaving groups. Also disclosed herein are methods for making such compounds and formulating pharmaceutical compositions thereof. Methods for administering the disclosed compounds to subjects, particularly to treat hyperproliferative disorders, also are disclosed.
Claims54
A compound of the formula:
- wherein A+ represents an ammonium species selected from quaternary ammonium, the conjugate acid of a basic amino acid, aliphatic ammonium, heterocyclic ammonium, aromatic ammonium, substituted and unsubstituted pyridinium, guanidinium, and amidinium;
- and
- X and Y independently represent leaving groups.
A salt comprising an isophosphoramide mustard anion and an ammonium cation.
A pharmaceutical composition comprising a salt of isophosphoramide mustard and an amine base;
- and a pharmaceutically acceptable carrier.
A compound of the formula:
A compound of the formula:
- wherein A+ represents an acyclic aliphatic ammonium that includes one or more substitutions with a hydroxyl group;
- and X and Y independently are selected from the halogens and the sulfonates.
A sterile aqueous solution suitable for administration to a human patient, comprising a compound dissolved directly therein of the formula:
- wherein A+ represents an ammonium species selected from quaternary ammonium, the conjugate acid of a basic amino acid, aliphatic ammonium, heterocyclic ammonium, aromatic ammonium, substituted and unsubstituted pyridinium, guanidinium, and amidinium;
- and X and Y independently represent leaving groups.
A sterile aqueous solution suitable for administration to a human patient, having dissolved directly therein
- (i). a compound of the formula:
- wherein X and Y independently represent leaving groups, and
- (ii). an ammonium species selected from quaternary ammonium, the conjugate acid of a basic amino acid, aliphatic ammonium, heterocyclic ammonium, aromatic ammonium, substituted and unsubstituted pyridinium, guanidinium, and amidinium;
- wherein the compound in the solution has a half-life at room temperature that is equal or greater to five times the half-life of the compound in solution in the absence of the ammonium species.
A sterile lyophilisate of a compound of the formula:
- wherein A+ represents an ammonium species selected from quaternary ammonium, the conjugate acid of a basic amino acid, aliphatic ammonium, heterocyclic ammonium, aromatic ammonium, substituted and unsubstituted pyridinium, guanidinium, and amidinium;
- and X and Y independently represent leaving groups,
- and wherein the lyophilisate is formed from a sterile solution of the compound dissolved in water.
A sterile lyophilisate formed from an aqueous solution having dissolved therein a compound of the formula
- and an acyclic aliphatic ammonium that includes one or more substitutions with a hydroxyl group;
- and X and Y independently are selected from the halogens and the sulfonates, wherein the compound in the lyophilisate does not substantially undergo decomposition during storage of the lyophilisate for ten (10) months at −20° C.
Dependencies are inferred from the claim text.