Prodrugs of hydroxymethylpentamethylmelamine: a principal active metabolite of the antineoplastic agent hexamethylmelamine.

Author(s): Ghodrati F, Lavoie EJ

Affiliation(s): Department of Pharmaceutical Chemistry, College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855.

Publication date & source: 1994-02, Drug Des Discov., 11(2):135-47.

Publication type:

Hexamethylmelamine is in clinical use as an antineoplastic agent. Derivatives and prodrugs of two of its biologically-active metabolites were prepared in an effort to alter its solubility and to enhance bioavailability. In this study prodrugs of pentamethylmelamine and hydroxymethylpentamethylmelamine were synthesized. Among the compounds prepared were N-(methoxymethyl)pentamethylmelamine, N-(ethylthiomethyl)pentamethylmelamine, and several N'-alkyl-N'-methyl-N-(aminomethyl)pentamethylmelamine and N'-aryl-N'-methyl-N-(aminomethyl)pentamethylmelamine derivatives. The aqueous solubility of these prodrugs relative to hexamethylmelamine was compared. The half-lives of these prodrugs were also determined at pH 7.4. The more stable derivatives were assayed at pH 6.4. These prodrugs represent a novel approach for the delivery of the suspect active metabolite of hexamethylmelamine, hydroxymethylpentamethylmelamine.