唑来膦酸的合成研究

Study on synthesis of zoledronic acid

唑来膦酸属于第三代双膦酸药物,是含氮杂环双膦酸和吡啶双膦酸盐的骨吸收抑制剂。由于具有活性强、毒性低等优点,因而具有良好的应用前景。对唑来膦酸工艺进行了改进,通过加入分散剂解决了膦酸化步骤的固化问题。探索出了一种有效的分散剂,解决了双膦酸类化合物制备过程中膦酸化步骤容易固化结块制约工业化生产的问题,经工业放大生产被证明该改进工艺是可行的,合理的。

Zoledronic acid is the third generation bisphosphonate drug. It has the potential for other applications due to it＇s effectiveness in treatment of arresting bone deterioration and restoring normocalcemia in patients with hypercalcemia of malignancy, metastatic bone disease, Paget＇s disease, and osteoporosis. The synthetic process of zoledronic acid were studied and improved. The solidification problems were solved by adding the dispersing agent. The common solification problems in phosphonic acidation of bisphosphonates process were dissolbed by applying a dispersant agent which successfully overcomes the problem of solidification of the reation mixture and the disadvan- tage of the present route.