Synthesis and study of alendronate derivatives as potential prodrugs of alendronate sodium for the treatment of low bone density and osteoporosis

  • Vachal P
  • Hale J
  • Lu Z
 et al. 
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Abstract

Alendronate derivatives were evaluated as potential prodrugs for the osteoporosis drug alendronate sodium in an attempt to enhance the systemic exposure after oral administration. An investigation of the chemical behavior of alendronate derivatives led to development of practical synthetic strategies and prediction of each structural class's prodrug potential. Pharmacokinetic studies of N-myristoylalendronic acid revealed that 25% have been converted in vivo after i.v. administration in rat, providing an important proof-of-concept for this strategy.

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Authors

  • Petr Vachal

  • Jeffrey J. Hale

  • Zhe Lu

  • Eric C. Streckfuss

  • Sander G. Mills

  • Malcolm MacCoss

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