Amino acid derivatives of dapsone as water-soluble prodrugs

Nancy L. Pochopin, William N. Charman, Valentino J. Stella

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54 Citations (Scopus)


Amino acid amides of dapsone, a primary aromatic amine, have been synthesized as potential water-soluble, chemically stable prodrugs that target peptidase enzymes for cleavage to the parent drug in vivo. The alanine, glycine, leucine, lysine, and phenylalanine derivatives of dapsone all exhibited greater aqueous solubility, as their salts, than the parent compound. Solution half-lives ranged from 1 to 12 h at pH 7.4 and 73°C. In the presence of aminopeptidases and in whole blood, rapid enzymatic hydrolysis resulted in quantitative conversion to dapsone. The good chemical stability and rapid enzymatic hydrolysis in vitro suggest that these compounds would be good prodrug candidates.

Original languageEnglish
Pages (from-to)157-167
Number of pages11
JournalInternational Journal of Pharmaceutics
Issue number2
Publication statusPublished - 25 Jul 1995


  • Amino acid
  • Aminopeptidase
  • Blood
  • Dapsone
  • Prodrug
  • Stability

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