A novel hydroxy-bisphosphonic acid prodrug as a candidate for the delivery of ibuprofen to bone

Abstract

Active targeting with controlled delivery of anti-inflammatory drugs to the bone is not sufficiently explored. In this study, concise and novel synthesis of a hydroxy-bisphosphonic acid (HBPA) prodrug containing ibuprofen is described. The key step consisted of preparing the HBPA function from a carboxylic acid precursor, in mild conditions and using appropriate Arbuzov reactions with tris(trimethylsilyl)phosphite. This prodrug would be an excellent candidate for the treatment of bone inflammation diseases such as rheumatoid arthritis.

Graphical Abstract

Keywords:

• Arbuzov reaction
• bone inflammation
• carboxylic acid
• drug delivery
• hydroxy-bisphosphonic acid
• prodrug