title: Prodrugs of hydroxymethylpentamethylmelamine: a principal active metabolite of the antineoplastic agent hexamethylmelamine.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855.
authors.forename: F
authors.initials: F
authors.lastname: Ghodrati
authors.forename: E J
authors.initials: EJ
authors.lastname: Lavoie
mesh_terms: D006585:Altretamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism*; D004355:Drug Stability; D006207:Half-Life; D006868:Hydrolysis; D011355:Prodrugs / Q000138:chemical synthesis / Q000378:metabolism*; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; C024065:pentamethylmonomethylolmelamine; D006585:Altretamine