183370-70-9

Upstream product

• 5557-81-3 L-alanine benzyl ester hydrochloride 
• 770-12-7 O-phenyl phosphorodichloridate 
• 108-95-2 phenol 
• 17831-01-5 H-Ala-OBzl 
• 100-51-6 benzyl alcohol 
• 104-15-4 toluene-4-sulfonic acid 
• 42854-62-6 L-alanine benzyl ester p-toluenesulfonate 

Downstream Products

• 936616-56-7 C₂₇H₃₀N₃O₁₀P 
• 936616-49-8 phenyl-[benzyloxy-L-alaninyl]-[((1R,3R,4R,7R)-3-(adenine-9-yl)-7-hydroxy-2,5-dioxabicyclo[2:2:1]heptane-1-yl)methyl] phosphate 
• 936616-59-0 C₂₇H₃₀N₃O₁₀P 
• 936616-53-4 phenyl-[benzyloxy-L-alaninyl]-[((1R,3R,4R,7S)-3-(adenine-9-yl)-7-hydroxy-2,5-dioxablcyclo[2:2:1]heptane-1-yl)methyl] phosphate 
• 1029347-62-3 2',3'-O,O-isopropylidene-β-2'-methyl-guanosine 5'-O-[phenyl(benzoxy-L-alaninyl)] phosphate 
• 1170666-24-6 C₃₁H₃₃N₈O₉P 
• 1228877-52-8 C₂₇H₂₉IN₃O₉P 
• 1268354-32-0 C₃₀H₃₂ClN₄O₈P 
• 1321581-04-7 C₂₅H₂₅ClF₂N₃O₉P 
• 1321580-98-6 C₂₅H₂₅F₂IN₃O₉P 
• 1321581-03-6 C₂₅H₂₅BrF₂N₃O₉P 

Relevant academic research and scientific papers

Influence of 4′-Substitution on the Activity of Gemcitabine and Its ProTide against VZV and SARS-CoV-2

In addition to its therapeutic value as a chemotherapy drug, gemcitabine is of ongoing interest to the scientific community for its broad-spectrum antiviral activity. Herein the synthesis of 4′-methoxy- and 4′-fluoro-substituted gemcitabine analogues along with their phosphoramidate prodrugs is described. Among these derivatives, 4′-fluorogemcitabine proved to be active against varicella zoster virus (VZV, TK+ strain) with an EC50 of 0.042 μM and produced significant cytotoxicity (CC50 = 0.11 μM). Upon derivatization of this trifluoro nucleoside as its prodrug, decreased anti-VZV activity was observed, but with a concomitantly improved selectivity index (SI = 36). When this prodrug was tested against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its antiviral activity (EC50 = 0.73 μM) was comparable to or slightly lower than its cytotoxic concentration in measurements of cell growth and cell morphology, respectively.

Generation of Stable Isopentenyl Monophosphate Aryloxy Triester Phosphoramidates as Activators of Vγ9Vδ2 T Cells

Aryloxy triester phosphoramidate prodrugs of the monophosphate derivatives of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) were synthesized as lipophilic derivatives that can improve cell uptake. Despite the structural similarity of IPP and DMAPP, it was noted that their phosphoramidate prodrugs exhibited distinct stability profiles in aqueous environments, which we show is due to the position of the allyl bond in the backbones of the IPP and DMAPP monophosphates. As the IPP monophosphate aryloxy triester phosphoramidates showed favorable stability, they were subsequently investigated for their ability to activate Vγ9/Vδ2 T cells and they showed promising activation of this subset of T cells. Together, these findings represent the first report of IPP and DMAPP monophosphate prodrugs and the ability of IPP aryloxy triester phosphoramidate prodrugs to activate Vγ9/Vδ2 T cells highlighting their potential as possible immunotherapeutics.

2,4,7-SUBSTITUTED-7-DEAZA-2'-DEOXY-2'-FLUOROARABINOSYL NUCLEOSIDE AND NUCLEOTIDE PRO-DRUGS AND USES THEREOF

The present disclosure is concerned with 2,4,7-substituted-7-deaza-2'-deoxy-2'- fluoroarabinosyl nucleoside and nucleotide prodrugs that are capable of inhibiting viral infections and methods of treating viral infections such as, for example, human immunodeficiency virus (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), human cytomegalovirus (HCMV), chicken pox, infectious mononucleosis, mumps, measles, rubella, shingles, ebola, viral gastroenteritis, viral hepatitis, viral meningitis, human metapneumovirus, human parainfluenza virus type 1, parainfluenza virus type 2, parainfluenza virus type 3, respiratory syncytial virus, viral pneumonia, Chikungunya virus (CHIKV), Venezuelan equine encephalitis (VEEV), dengue (DENV), influenza, West Nile virus (WNV), zika (ZIKV), 229E, NL63, OC43, HKU1, Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus disease 2019 (SARS-CoV-2), using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Radiosynthesis of [18F]-labelled pro-nucleotides (ProtIDes)

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of P

Aryloxy Triester Phosphoramidates as Phosphoserine Prodrugs: A Proof of Concept Study

The specific targeting of protein-protein interactions by phosphoserine-containing small molecules has been scarce due to the dephosphorylation of phosphoserine and its charged nature at physiological pH, which hinder its uptake into cells. To address these issues, we herein report the synthesis of phosphoserine aryloxy triester phosphoramidates as phosphoserine prodrugs that are enzymatically metabolized to release phosphoserine. This phosphoserine-masking approach was applied to a phosphoserine-containing inhibitor of 14-3-3 dimerization, and the generated prodrugs exhibited improved pharmacological activity. Collectively, this provided a proof of concept that the masking of phosphoserine with biocleavable aryloxy triester phosphoramidate masking groups is a viable intracellular delivery system for phosphoserine-containing molecules. Ultimately, this will facilitate the discovery of phosphoserine-containing small-molecule therapeutics.

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

Phosphoramidate derivatives of nucleoside compounds and uses of derivatives

The invention belongs to the technical field of medicines, and relates to phosphoramidate derivatives of nucleoside compounds, uses of the phosphoramidate derivatives, and a pharmaceutical compositioncontaining the compounds. The derivatives and pharmaceu

Nucleoside phosphate/amide derivative and medical application thereof

The invention relates to a nucleoside phosphate/amide derivative shown in the formula I and isomers, nontoxic pharmaceutically acceptable salts and solvates thereof. The formula I is shown in the description. In the formula I, Nu represents nucleoside res

NOVEL SMALL MOLECULE DRUG CONJUGATES OF GEMCITABINE DERIVATIVES

Disclosed are compounds having formula (I) or a pharmaceutically acceptable salt, ester, amide, solvate, or stereoisomer thereof, wherein L, Y1, Y2, Y3, Y4, Y5, Z1, Z2, Z3, Z4, Z5, Z6, and Effector are each as defined in the specification; compositions thereof; uses thereof; and methods of use thereof.

4'-THIO-NUCLEOTIDE AND -NUCLEOSIDE PRODRUGS FOR THE TREATMENT OF CANCER

The present disclosure is concerned with 4'-thio nucleotide and nucleoside compounds for the treatment of various cancers such as, for example, sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, bladder cancer, thyroid cancer, testicular cancer, pancreatic cancer, endometrial cancer, melanomas, gliomas, leukemias, lymphomas, chronic myeloproliferative disorders, myelodysplastic syndromes, myeloproliferative neoplasms, and plasma cell neoplasms (myelomas). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.