879895-44-0

Upstream product

• 40615-36-9 4,4'-dimethoxytrityl chloride 
• 50-91-9 5-Fluoro-2'-deoxyuridine 
• 104495-48-9 1-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-5-fluoropyrimidine-2,4(1H,3H)-dione 
• 18162-48-6 tert-butyldimethylsilyl chloride 

Relevant academic research and scientific papers

3'- O - And 5'- O -Propargyl Derivatives of 5-Fluoro-2'-Deoxyuridine: Synthesis, Cytotoxic Evaluation and Conformational Analysis

A series of new 3'-O- and 5'-O-propargyl derivatives of 5-fluoro-2'-deoxyuridine (1-4) was synthesized by means of propargyl reaction of properly blocked nucleosides (2,4), followed by the deprotection reaction with ammonium fluoride. The synthesized propargylated 5-fluoro-2'-deoxyuridine analogues (1-4) were evaluated for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7), using the sulforhodamine B (SRB) assay. The highest activity and the best SI coefficient in all of the investigated cancer cells were displayed by 3'-O-propargyl-5-fluoro-2'-deoxyuridine (1), and its activity was higher than that of the parent nucleoside. The other new compounds exhibited moderate activity in all of the used cell lines.

Fluorine at the C5 Position of 2′-Deoxyuridine Enhances Repair of a O4-Methyl Adduct by O6-Alkylguanine DNA Alkyltransferases

Alkylation damage at the O6- and O4-atoms of 2′-deoxyguanosine (dG) and thymidine (T), respectively, can be removed by O6-alkylguanine-DNA alkyltransferases (AGTs). Previous studies have shown that human AGT (hAGT) repairs

Discovery of an Orally Active and Liver-Targeted Prodrug of 5-Fluoro-2′-Deoxyuridine for the Treatment of Hepatocellular Carcinoma

We report a series of novel O-(substituted benzyl) phosphoramidate prodrugs of 5-fluoro-2′-deoxyuridine for the treatment of hepatocellular carcinoma. Through structure optimization, the o-methylbenzyl analog (1t) was identified as an orally bioavailable and liver-targeted lead compound. This lead prodrug is well-tolerated at a dose up to 3 g/kg in Kuming mice via oral administration. An efficacy study demonstrated that it possesses good inhibitory effect (61.67% and 72.50%, respectively) on tumor growth in a mouse xenograft model. A metabolism study in Sprague-Dawley rats suggested that 1t can release the desired 5′-monophosphate in the liver with high liver-targeting index.

Delivery of floxuridine derivatives to cancer cells by water-soluble organometallic cages

The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene (pPriC6H4Me) ruthenium building blocks and 2,5-dioxydo-1,4-benzoquinonato (dobq) or 5,8-dioxydo-1,4-naphthoquinonato (donq) bridges, in the presence of a pyrenyl-nucleoside derivatives (pyreneR), affords the triangular prismatic host-guest compounds [(pyrene-R)?Ru6(pPriC 6H4Me)6(tpt)2(dobq) 3]6+ ([(pyrene-R)?1]6+) and [(pyrene-R)?Ru6(pPriC6H4Me) 6(tpt)2(donq)3]6+ ([(pyrene-R)?2]6+), respectively. The inclusion of six monosubstitutedpyrenyl-nucleosides (pyrene-R1 = 5′-(1-pyrenyl butanoate)-2′-deoxyuridine, pyrene-R2 = 5-fluoro-5′-(1-pyrenyl butanoate)-2′-deoxyuridine, pyrene-R3 = 5′-{N-[1-oxo-4-(1-pyrenyl) butyl]-glycyl}-2′-deoxyuridine, pyrene-R4 = 5-fluoro-5′-{N-[1-oxo-4- (1-pyrenyl)butyl]-glycyl}-2′-deoxyuridine, pyrene-R5 = 5-fluoro-5′-{N-[1-oxo-4-(1-pyrenyl)butyl]-phenylalanyl} -2′-deoxyvuridine, pyrene-R6 = 5-fluoro-5′-{N-[1-oxo-4-(1-pyrenyl) butyl]-phenylalanyl}-2′-deoxyuridine) has been accomplished. The carceplex nature of [(pyrene-R)?1]6+ with the pyrenyl moiety firmly encapsulated in the hydrophobic cavity of the cage with the nucleoside groups pointing outward was confirmed by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS), while the host-guest nature of [(pyrene-R)?2] 6+ was studied in solution by NMR techniques. In contrast to the floxuridine compounds used in the clinic, the host-guest complexes are highly water-soluble. Consequently, the cytotoxicities of these water-soluble compounds have been established using human ovarian A2780 and A2780cisR cancer cells. All the host-guest systems are more cytotoxic than the empty cages alone [1][CF3SO3]6 (IC50 = 23 μM) and [2][CF3SO3]6 (IC50 = 10 μM), the most active compound [pyrene-R4?1][CF3SO3] 6being 2 orders of magnitude more cytotoxic (IC50 = 0.3 μM) on these human ovarian cancer cell lines (A2780 and A2780cisR).