1365246-84-9Relevant academic research and scientific papers
NRTI THERAPIES
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Page/Page column 60-61; 78, (2020/07/14)
Polymer-of-prodrug (POP) materials enable new nucleoside reverse transcriptase inhibitor (NRTI) therapy strategies. The materials are prodrugs of NRTIs in the form of polymers. Suitable materials include products which are polymeric NRTI delivery systems comprising polymeric materials which are capable of degradation after administration to release NRTIs or NRTI prodrugs which themselves are capable of metabolism to the parent NRTIs. The NRTIs may optionally be selected from tenofovir (TFV), emtricitabine (FTC), lamivudine (3TC) and MK-8591 (EFdA). The invention facilitates long-acting (LA) regimens. Constructs of the materials may be in the form of injectable compositions or implants.
Synthesis and anti-HIV activities of glutamate and peptide conjugates of nucleoside reverse transcriptase inhibitors
Agarwal, Hitesh K.,Chhikara, Bhupender S.,Quiterio, Megrose,Doncel, Gustavo F.,Parang, Keykavous
experimental part, p. 2672 - 2687 (2012/06/01)
Mono-, di-, and trinucleoside conjugates of glutamate or peptide scaffolds containing nucleoside reverse transcriptase inhibitors were synthesized. Among dinucleoside glutamate ester derivatives, N-myristoylated derivatives showed significantly higher anti-HIV activity than the corresponding N-acetylated conjugates against cell-free virus. Myristoyl-Glu(3TC)-FLT (46, EC50 = 0.3-0.6 μM) and myristoyl-Glu(FTC)-FLT (47, EC50 = 0.1-0.4 μM) derivatives were the most active glutamate-dinucleoside conjugates. A trinucleoside glutamate derivative containing AZT, FLT, and 3TC (34, EC 50 = 0.9-1.4 μM) exhibited higher anti-HIV activity than AZT and 3TC against cell-free virus. Compound 34 also exhibited higher anti-HIV activity against multidrug (IC50 = 5.9 nM) and NNRTI (IC50 = 12.9 nM) resistant viruses than parent nucleosides. The physical mixture containing FLT-succinate, AZT, 3TC, and glutamic acid exhibited 115-fold less activity against cell associated virus (EC50 = 91.9 μM) when compared to 34 (EC50 = 0.8 μM). Other conjugates showed less or comparable potency to that of the corresponding physical mixtures.
