Zhu Z, Chen H G, Goel O P, Chan O H, Stilgenbauer L A, Stewart B H
Chemical Development, Parke-Davis Pharmaceutical Research, Arbor, MI 48105, USA.
Bioorg Med Chem Lett. 2000 May 15;10(10):1121-4. doi: 10.1016/s0960-894x(00)00183-9.
In the preparation of phosphate prodrugs of PD154075, several strategies of linking a phosphate group to the indole moiety were studied. A novel linker, p-hydroxymethylbenzoyloxymethoxycarbonyl, was discovered to provide the phosphate prodrug of PD154075 (compound 9) with significantly increased aqueous solubility, sufficient stability in aqueous solution and good bio-reconversion in vivo.
在制备PD154075的磷酸酯前药时，研究了几种将磷酸基团连接到吲哚部分的策略。发现了一种新型连接基对羟基甲基苯甲酰氧基甲氧基羰基，它能使PD154075的磷酸酯前药（化合物9）具有显著提高的水溶性、在水溶液中有足够的稳定性以及在体内良好的生物转化性能。
