Hydrolysis of the Prodrug, 2′, 3′, 5′ -Triacetyl-6-azauridine

C. M. Riley, M. A. Mummert, J. Zhou, R. L. Schowen, D. G. Vander Velde, M. D. Morton, M. Slavik

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Purpose. The purposes were to study the kinetics of hydrolysis of 2′,3′,5′-triacetyl-6-azauridine (1) in aqueous solution (µ = 0.5) and to identify the main intermediates and products of the reaction. Methods. A stability indicating isocratic LC assay was used to study the rate of degradation of 1 A gradient LC assay was used to study the time courses of the degradants. The products of hydrolysis were isolated by preparative liquid chromatography and identified by 1H-NMR and CI-MS. The pKa value was obtained by potentiometric titration. Results. At 36.8°C, the pH-rate profile of 1 in water was adequately described by a four-term rate equation. The intermediates were identified as the primary and secondary di-acetates, and the primary and secondary mono-acetates. The final product was 6-azauridine. Conclusions. A simplified kinetic scheme could be used to describe the concentration-time profiles of 1, the intermediates and the final product.

Original languageEnglish (US)
Pages (from-to)1361-1370
Number of pages10
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Volume12
Issue number9
DOIs
StatePublished - Sep 1995

Keywords

  • 2′,3′,5′-triacetyl-6-azauridine
  • CI-MS
  • NMR
  • arrhenius plots
  • hydrolysis
  • liquid chromatography
  • pH-profile
  • prodrug

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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