Wu Zhimeng, Drach John C, Prichard Mark N, Yanachkova Milka, Yanachkov Ivan, Bowlin Terry L, Zemlicka Jiri
Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
Antivir Chem Chemother. 2009 Sep 25;20(1):37-46. doi: 10.3851/IMP782.
Following the example of L-valine prodrugs of antiviral nucleoside analogues, L-valine ester of cyclopropavir (valcyclopropavir) was synthesized.
The known tetrahydropyranylcyclopropavir was transformed to N-(tert-butoxycarbonyl)-L-valine ester, which was deprotected to valcyclopropavir.
Stability of valcyclopropavir towards hydrolysis at pH 7.0 roughly corresponded to that of valganciclovir. Valcyclopropavir inhibited replication of human cytomegalovirus (HCMV, Towne and AD169 strains) to approximately the same extent as the parent drug cyclopropavir. Pharmacokinetic studies in mice established that the oral bioavailability of valcyclopropavir was 95%.
The prodrug valcyclopropavir offers some improved therapeutic parameters over the parent compound cyclopropavir.
以抗病毒核苷类似物的L-缬氨酸前药为范例，合成了环丙沙星的L-缬氨酸酯（缬环丙沙星）。
将已知的四氢吡喃基环丙沙星转化为N-（叔丁氧羰基）-L-缬氨酸酯，然后脱保护得到缬环丙沙星。
缬环丙沙星在pH 7.0时的水解稳定性大致与缬更昔洛韦相当。缬环丙沙星抑制人巨细胞病毒（HCMV，汤氏株和AD169株）复制的程度与母体药物环丙沙星大致相同。在小鼠体内进行的药代动力学研究表明，缬环丙沙星的口服生物利用度为95%。
前药缬环丙沙星相对于母体化合物环丙沙星具有一些改善的治疗参数。
