Boojamra Constantine G, Parrish Jay P, Sperandio David, Gao Ying, Petrakovsky Oleg V, Lee Sharon K, Markevitch David Y, Vela Jennifer E, Laflamme Genevieve, Chen James M, Ray Adrian S, Barron Abraham C, Sparacino Mark L, Desai Manoj C, Kim Choung U, Cihlar Tomas, Mackman Richard L
Gilead Science, Inc, Foster City, CA 94404, USA.
Bioorg Med Chem. 2009 Feb 15;17(4):1739-46. doi: 10.1016/j.bmc.2008.12.028. Epub 2008 Dec 24.
A diphosphate of a novel cyclopentyl based nucleoside phosphonate with potent inhibition of HIV reverse transcriptase (RT) (20, IC(50)=0.13 microM) has been discovered. In cell culture the parent phosphonate diacid 9 demonstrated antiviral activity EC(50)=16 microM, within two-fold of GS-9148, a prodrug of which is currently under clinical investigation, and within 5-fold of tenofovir (PMPA). In vitro cellular metabolism studies using 9 confirmed that the active diphosphate metabolite is produced albeit at a lower efficiency relative to GS-9148.
已发现一种新型环戊基核苷膦酸酯的二磷酸盐，它对HIV逆转录酶（RT）具有强效抑制作用（20，IC(50)=0.13微摩尔）。在细胞培养中，母体膦酸二酸9表现出抗病毒活性，EC(50)=16微摩尔，与GS-9148相差不到两倍，GS-9148的一种前药目前正在临床研究中，且与替诺福韦（PMPA）相差不到5倍。使用9进行的体外细胞代谢研究证实，尽管相对于GS-9148，活性二磷酸代谢物的产生效率较低，但仍可产生。
