217090-41-0

Upstream product

• 106-48-9 4-chloro-phenol 
• 67436-20-8 p-toluenesulfonic acid salt of (S)-α-alanine 
• 772-79-2 4-chlorophenylphosphorodichloridate 
• 2491-20-5 L-alanine methyl ester hydrochloride 

Downstream Products

• 222021-16-1 2',3'-didehydro-2',3'-dideoxythymidine 5'-(4-chlorophenyl (methoxyalaninyl)phosphate) 
• 936616-57-8 C₂₁H₂₅ClN₃O₁₀P 
• 936616-51-2 p-chloro-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 
• 936616-60-3 C₂₁H₂₅ClN₃O₁₀P 
• 936616-54-5 C₂₁H₂₄ClN₆O₈P 
• 1122511-04-9 C₂₉H₃₂ClN₂O₇P 
• 1122511-11-8 C₃₂H₃₄Cl₂N₃O₈P 
• 1122511-14-1 C₂₇H₂₉Cl₃N₃O₆P 
• 1122511-07-2 C₂₆H₃₆ClN₂O₆P 

Relevant academic research and scientific papers

Prodrug compound and application ofprodrug compound in treatment of cancer

The present invention provides a compound indicated by a formula (I), pharmaceutically acceptable salts or esters thereof, a pharmaceutical composition of the compound, and application of the compoundand the pharmaceutical composition in the inhibition or regulation of the activity of tyrosine kinase and treating disease symptoms or symptoms including cancer mediated by tyrosine kinase.

PRODRUGS OF THE TYROSINE KINASE INHIBITOR FOR TREATING CANCER

There are provided compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, useful for inhibition or modulation of the activity of tyrosine kinases and treatment of disease states or conditions mediated by tyrosine kinases, including cancers. (I)

Synthesis and biological evaluation of LNA phosphoramidates

The synthesis of LNA phosphoramidates is presented. The LNA phosphoramidates were evaluated for their ability to inhibit cell proliferation of the human prostate cancer cell line 15PC3. A number of the LNA phosphoramidates showed cell proliferation inhibition determined by the MTS assay. Copyright Taylor & Francis Group, LLC.

Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives

We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.

Phosphoramidate and phosphate prodrugs of (-)-β-D-(2R,4R)-dioxolane- thymine: Synthesis, anti-HIV activity and stability studies

A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity.

PHOSPHORAMIDATE PRODRUGS FOR TREATMENT OF VIRAL INFECTION

The invention concerns 2'-methyl ribonucleotide phosphoramidates which are neutral prodrugs which are converted in vivo to 2'- methyl ribonucleotide triphosphates. These compounds are useful in the treatment of viral infection. Of particular interest are prodrugs of a methylsulfonylhydrazinyl purine 2'-methyl nucleotide triphosphate: 2'methyl- N6-alkyl-N6- (N-methylsulfonamide) adenosine triphosphate and its 2-amino derivative.

CHEMICAL COMPOUNDS

Phosphoramidate derivatives of nucleotides and their use in the treatment of cancer are described. The base moieties of, for example, each of deoxyuridine, cytarabine, gemcitabine and citidine may be substituted at the 5-position. The phosphoramidate moiety has attached to the P atom an aryl-O moiety and an α-amino acid moiety. The α-amino acid moiety may correspond to or be derived from either a naturally occurring or a non-naturally occurring amino acid.