220592-67-6

Upstream product

• 108-95-2 phenol 
• 770-12-7 O-phenyl phosphorodichloridate 
• 72873-27-9 (S)-cyclohexyl 2-aminopropanoate 
• 41324-79-2 (S)-methyl-2-amino cyclohexyl acetate hydrochloride 

Downstream Products

• 1615696-46-2 (2S)-cyclohexyl 2-(((((2R,3R,4S,5R)-5-(2-amino-6-ethoxy-1H-purin-9(6H)-yl)-3-fluoro-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate 
• 1615696-55-3 (2S)-cyclohexyl 2-(((((2R,3R,4S,5R)-5-(2-amino-6-oxo-1H-purin-9(6H)-yl)-3-fluoro-4-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate 
• 1613589-83-5 C₆₈H₆₉F₂N₆O₁₀P 

Relevant academic research and scientific papers

Phosphoramidate derivative of nucleoside compound and application thereof

The invention belongs to the technical field of medicines, and relates to a phosphoramidate derivative of a nucleoside compound and application thereof, and a pharmaceutical composition containing thecompound. The phosphoramidate derivative can be used as

NICOTINAMIDE RIBOSIDE AND NICOTINAMIDE MONONUCLEOTIDE DERIVATIVES FOR USE IN THE TREATMENTS OF MITOCHONDRIAL-RELATED DISEASES

Provided herein are compounds of Formula (I): or a pharmaceutically acceptable salt thereof, and compositions comprising such compounds that are useful for increasing the amount of NAD+ in cells. Also disclosed are methods of using the disclosed compounds and compositions for treating mitochondrial-related diseases or disorders.

Anti-hepatitis b virus drug

The invention relates to a novel anti-hepatitis B virus drug represented in a formula I, and a nontoxic pharmaceutically acceptable salt and a hydrate thereof: (img file= 'DSA00000804267600011.TIF' wi= '739' he= '766' /), wherein R1 is alkyl or naphthenic base, of which the carbon number is 1-6, and R2 is H or alkyl of which the carbon number is 1-6.

ProTides of BVdU as potential anticancer agents upon efficient intracellular delivery of their activated metabolites

Nucleosides represent a major chemotherapeutic class for treating cancer, however their limitations in terms of cellular uptake, nucleoside kinase-mediated activation and catabolism are well-documented. The monophosphate pro-nucleotides known as ProTides represents a powerful strategy for bypassing the dependence on active transport and nucleoside kinase-mediated activation. Herein, we report the structural tuning of BVdU ProTides. Forty six phosphoramidates were prepared and biologically evaluated against three different cancer cell lines; murine leukemia (L1210), human CD4+T-lymphocyte (CEM) and human cervical carcinoma (HeLa). Twenty-fold potency enhancement compared to BVdU was achieved against L1210 cells. Interestingly, a number of ProTides showed low micromolar activity against CEM and HeLa cells compared to the inactive parent BVdU. The ProTides showed poor, if any measurable toxicity to non-tumourigenic human lung fibroblast cell cultures. Separation of four pairs of the diastereoisomeric mixtures and comparison of their spectral properties, biological activities and enzymatic activation rate is reported.

HCV POLYMERASE INHIBITORS

The invention provides compounds of the formula:(I) wherein B is a nucleobase selected from the groups (a) to (d) and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

HCV POLYMERASE INHIBITORS

The invention provides compounds of the formula (I) wherein B is a nucleobase selected from the groups (a) to (d): and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.

Application of ProTide technology to gemcitabine: A successful approach to overcome the key cancer resistance mechanisms leads to a new agent (NUC-1031) in clinical development

Gemcitabine is a nucleoside analogue commonly used in cancer therapy but with limited efficacy due to a high susceptibility to cancer cell resistance. The addition of a phosphoramidate motif to the gemcitabine can protect it against many of the key cancer resistance mechanisms. We have synthesized a series of gemcitabine phosphoramidate prodrugs and screened for cytostatic activity in a range of different tumor cell lines. Among the synthesized compounds, one in particular (NUC-1031, 6f) was shown to be potent in vitro. Importantly, compared with gemcitabine, 6f activation was significantly less dependent on deoxycytidine kinase and on nucleoside transporters, and it was resistant to cytidine deaminase-mediated degradation. Moreover, 6f showed a significant reduction in tumor volumes in vivo in pancreatic cancer xenografts. The ProTide 6f is now in clinical development with encouraging efficacy signals in a Phase I/II study, which strongly supports the ProTide approach to generate promising new anticancer agents.

HCV POLYMERASE INHIBITORS

The invention provides compounds of the formula:(I) which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.

Synthesis and Biological Evaluation of Purine 2′-Fluoro-2′-deoxyriboside ProTides as Anti-influenza Virus Agents

2′-Fluoro-2′-deoxyguanosine has been reported to have potent anti-influenza virus activity invitro and invivo. Herein we describe the synthesis and biological evaluation of 6-modified 2′-fluoro-2′-deoxyguanosine analogues and their corresponding phosphora