N-heterocyclic dronic acids: applications and synthesis
H R Hudson1, N J Wardle, S W A Bligh
1London Metropolitan University, 166-220 Holloway Rd., London, N7 8DB, UK.
Mini Reviews in Medicinal Chemistry
|February 7, 2012
Summary
Bisphosphonates, including dronic acids and their salts, are vital pharmaceuticals for treating bone-resorption diseases. This review critically examines their synthesis, focusing on improving the popular three-component condensation method.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Pharmacology
Background:
- Bisphosphonates are crucial pharmaceuticals for treating bone-resorption diseases.
- Their therapeutic potential extends to parasite inhibition, immunology, and cancer treatment.
- N-heterocyclic derivatives like zoledronic and risedronic acids are clinically significant.
Purpose of the Study:
- To critically review synthetic routes for dronic acids and their salts.
- To clarify inconsistencies in reported synthetic protocols.
- To propose a practical and improved synthetic procedure.
Main Methods:
- Literature review of synthetic methods for bisphosphonates.
- Analysis of the three-component condensation reaction (substituted acetic acid, phosphorous acid, phosphorus trichloride).
- Critical evaluation of reported protocols and reaction mechanisms.
Main Results:
- The three-component condensation is the most common route to valuable dronic acids.
- Significant diversity and contradictions exist in published synthetic protocols.
- A clarified and practical synthetic procedure is suggested.
Conclusions:
- Bisphosphonates are essential drugs with diverse applications.
- Standardization and clarification of synthetic routes are needed for efficient production.
- Further research into reaction mechanisms can optimize synthesis.
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