摘要
替诺福韦,化学名9-R-[(2-膦酸甲氧基)丙基)]腺嘌呤(PMPA),是一种新型开环膦酸核苷化合物,可有效抑制逆转录病毒的复制。由于其结构中膦酸部分在生理pH下以二价阴离子形式存在,极性太强不易通过生物膜,导致该类药物生物利用度和细胞渗透性差并且具有一定的肾毒性而难以作为药物使用,因此通常被做成前药以掩蔽膦酸部位的强荷电性,改善口服吸收效果和减轻毒副作用。本文对PMPA的前药,包括酯化前药、酯化酰胺化前药以及二聚体前药3个方面的研究进展进行综述。
Tenofovir, the 9-[2-（R）-（phosphonomethoxy） propyl] adenine （PMPA）, is an acyclic nucleoside phosphonate that has potent antiviral activity against both HIV and HBV. Despite its demonstrated antiviral potency, PMPA has limited oral bio- availability, poor cell penetration and moderate-to-severe renal toxicity, presumably resulting from the presence of two negative charges on the phosphonyl group. In order to improve the oral bioavailability and reduce the cytotoxicity, prodrug design is used to mask the high charge of the parent drug. In this paper, we review the advances on the prodrug of tenofovir from three aspects ： esterification, es- ter amidation and dimerization.
出处
《国际药学研究杂志》
CAS
2012年第5期414-419,424,共7页
Journal of International Pharmaceutical Research
