110522-47-9Relevant articles and documents
N4-[Alkyl-(hydroxyphosphono)phosphonate]-cytidine - New drugs covalently linking antimetabolites (5-FdU, araU or AZT) with bone-targeting bisphosphonates (alendronate or pamidronate)
Schott, Herbert,Goltz, Daniel,Schott, Timm C.,Jauch, Claudia,Schwendener, Reto A.
, p. 3520 - 3526 (2011)
Amino-bisphosphonates (alendronate, pamidronate) were covalently linked in a three step synthesis, with protected and triazolylated derivatives of therapeutically used nucleoside analogs (5-FdU, araC, AZT) by substitution of their triazolyl residue. From the deprotected and chromatographically purified reaction mixtures N4-[alkyl-(hydroxyphosphono) phosphonate]-cytidine combining two differently cytotoxic functions were obtained. This new family of bisphosphonates (BPs) contains as novelty an alkyl side chain with a cytotoxic nucleoside. The BPs moiety allows for a high binding to hydroxyapatite which is a prerequisite for bone targeting of the drugs. In vitro binding of 5-FdU-alendronate (5-FdU-ale) to hydroxyapatite showed a sixfold increased binding of these BPs as compared to 5-FdU. Exploratory cytotoxic properties of 5-FdU-ale were tested on a panel of human tumor cell lines resulting in growth inhibition ranging between 5% and 38%. The determination of IC 50-concentrations of the conjugate in Lewis lung carcinoma and murine macrophages showed an incubation time dependent growth inhibition with higher sensitivity towards the tumor cells. We assume that the antimetabolite-BPs can be cleaved into different active metabolites that may exert cytotoxic and other therapeutic effects. However, the underlying mechanisms of these promising new antimetabolite-BPs conjugates remain to be evaluated in future experiments.
High purity 5 - fluoro - deoxy uracil nucleoside preparation method
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Paragraph 0108; 0109; 0110; 0111; 0112; 0113; 0114, (2017/08/25)
The invention discloses a preparation method of high-purity 5-fluro-deoxyuridine. The preparation method comprises the following steps: (A) mixing a 5-fluro-deoxyuridine derivative as shown in a structural formula B and a reagent capable of removing hydroxyl protecting groups, and reacting at the temperature of 5-40 DEG C, thereby obtaining a reaction system A; (B) dissolving the reaction system A in an organic solvent, and crystallizing at the temperature of 0-15 DEG C, thereby obtaining the 5-fluro-deoxyuridine as shown in a structural formula A. The reagent for removing the hydroxyl protecting groups is selected from ammonia water and methanol amine, an aqueous solution of sodium hydroxide and potassium hydroxide, glacial acetic acid, trifluoroacetic acid or tetrabutylammonium fluoride.
Regioselective acylation of nucleosides and their analogs catalyzed by Pseudomonas cepacia lipase: enzyme substrate recognition
Li, Ning,Zong, Min-Hua,Ma, Ding
supporting information; experimental part, p. 1063 - 1068 (2009/04/11)
The substrate recognition of Pseudomonas cepacia lipase in the acylation of nucleosides was investigated by means of rational substrate engineering for the first time. P. cepacia lipase displayed excellent 3′-regioselectivities (96 to >99%) in the lauroyl
