N-heterocyclic dronic acids: Applications and synthesis

H. R. Hudson, N. J. Wardle, S. W.A. Bligh, I. Greiner, A. Grün, G. Keglevich

Research output: Contribution to journalReview article

36 Citations (Scopus)


Substituted hydroxymethylenebisphosphonic acid derivatives - either as dronic acids or their dronate sodium salts, are important pharmaceuticals in the treatment of diseases arising from excessive bone-resorption. Potential has also been identified in areas ranging from parasite-growth inhibition to immunological and cancer therapeutics. Representative clinically relevant N-heterocyclic derivatives include zoledronic and risedronic acids. The biochemical background and mechanism of action of these drugs are discussed, along with trends in structural development and future prospects. Synthetic routes to dronates are then summarized. The most popular route to valuable dronic acids involves the 3- component condensation of a substituted acetic acid, phosphorous acid, and phosphorus trichloride. However, the protocols recorded in the literature are very diverse. This review gives a critical account of reported methods, explores the contradictions and suggests a practical synthetic procedure after clarifying the inconsistencies described. Possible mechanisms of the reaction are also discussed.

Original languageEnglish
Pages (from-to)313-325
Number of pages13
JournalMini-Reviews in Medicinal Chemistry
Issue number4
Publication statusPublished - Apr 1 2012



  • Anti-cancer
  • Anti-parasitic
  • Bone disease
  • Dronates
  • Practical synthesis
  • Reaction mechanism
  • Risedronic acid
  • Zoledronic acid

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Cancer Research

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