[EN] NUCLEOSIDE PRODRUGS AND USES RELATED THERETO<br/>[FR] PROMÉDICAMENTS NUCLÉOSIDIQUES ET LEURS UTILISATIONS
申请人:UNIV EMORY
公开号:WO2021035214A1
公开(公告)日:2021-02-25
Disclosed are acyclic nucleoside prodrugs with improved metabolic stability and oral bioavailability. In general, the prodrugs are derivatives of acyclic nucleoside phosphonates containing a lipid-like moiety that can increase oral absorption and subsequent stability in the liver and plasma. Preferably, the lipid-like moiety can resist enzyme-mediated ω-oxidation, such as ω -oxidation catalyzed by cytochrome P450 enzymes. Also disclosed are pharmaceutical formulations of the acyclic nucleoside prodrugs. The acyclic nucleoside prodrugs and pharmaceutical formulations thereof can be used to treat viral infections, such as HIV infections, and/or viral-associated cancer, such as HPV-associated cancers.
揭示了具有改善代谢稳定性和口服生物利用度的非环核苷前药。一般来说,这些前药是非环核苷膦酸酯的衍生物,含有类似脂质的基团,可以增加口服吸收并在肝脏和血浆中提高稳定性。最好,类似脂质的基团可以抵抗酶介导的ω-氧化,例如细胞色素P450酶催化的ω-氧化。还揭示了非环核苷前药的药物配方。这些非环核苷前药及其药物配方可用于治疗病毒感染,如HIV感染,和/或病毒相关癌症,如HPV相关癌症。