Abstract
1-[((S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl]cytosi ne (cyclic [cHPMPC]) was evaluated as a novel antiviral agent in comparison with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). Evaluation for in vitro activity against herpes simplex virus type 2 in MA-104 and MRC-5 cells showed that both cHPMPC and HPMPC have comparable activities and cytotoxicities. cHPMPC was found to be stable on incubation in human plasma and human liver homogenates. Intracellular metabolism studies revealed that cHPMPC was converted inside of the cells to HPMPC and then to the monophosphate, the diphosphate, and the monophosphate choline metabolites. In a mouse herpes simplex virus type 2 encephalitis model, both cHPMPC and HPMPC exhibited similar potencies in vivo. Nephrotoxicity, which is the dose-limiting toxicity of HPMPC, was assessed in a 14-day repeated-dose toxicity study in rats; cHPMPC has an improved safety margin of > or = 13-fold over that of HPMPC.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
