论文部分内容阅读
目的开发一条合成新型Na+依赖性葡萄糖共转运体2(SGLT2)抑制剂6-脱氧canagliflozin的简便实用的路线,并研究其可供药用的晶型。方法利用6-脱氧葡萄糖片段和含噻吩的苷元片段作为起始原料,经过3步反应合成了目标分子6-脱氧canagliflozin。使用从溶剂中结晶的方法来制备不同晶型,使用粉末X-射线衍射和差热分析来测定晶型。结果得到了一条简便实用的合成6-脱氧canagliflozin的路线,并获得了其2个晶型和1个与L-脯氨酸的共结晶。结论新合成路线具有步骤短、产率高的优点。6-脱氧canagliflozin的晶型B比较稳定,可以作为其最佳药用形式。
Objective To develop a simple and practical route to synthesize 6-deoxy canagliflozin, a novel Na + -dependent glucose transporter 2 (SGLT2) inhibitor, and to study its pharmacokinetic properties. Methods Using 6-deoxyglucose and thiophene-containing aglycone fragments as starting materials, the target molecule 6-deoxy canagliflozin was synthesized through 3 steps. Different crystalline forms were prepared using a method of crystallization from a solvent, and crystalline forms were determined using powder X-ray diffraction and differential thermal analysis. As a result, a simple and practical route for the synthesis of 6-deoxy canagliflozin was obtained and two crystalline forms and one co-crystal with L-proline were obtained. Conclusion The new synthetic route has the advantages of short steps and high yield. Form B of 6-deoxy canagliflozin is relatively stable and can be used as its best pharmaceutical form.