69304-47-8

Usage

Uses

Used in Pharmaceutical Industry:
Brivudine is used as a pharmaceutical intermediate for the development of anti-viral medications.
Used in Anti-Herpes Medication:
Brivudine is used as an anti-Herpes medication, specifically for the treatment of herpes simplex virus infections. Its antiviral properties make it an effective treatment option for controlling the spread of the virus and alleviating symptoms.
Used in Neuronal Differentiation:
Brivudine is used as an inducer of neuronal differentiation in human reporter cell lines and adult stem cells. This application has potential implications for regenerative medicine and the development of treatments for neurological disorders.

InChI:InChI=1/C13H17Cl3N4.2ClH/c1-20(5-2-14)8-9-6-10(15)12(11(16)7-9)19-13-17-3-4-18-13;;/h6-7H,2-5,8H2,1H3,(H2,17,18,19);2*1H

Upstream product

• 951-78-0 2'-deoxyuridine 
• 69304-49-0 (E)-5-(2-bromovinyl)uracil 
• 139546-03-5 3-[2-deoxy-β-D-ribofuranosyl]-furo[2,3-d]pyrimidin-2(3H)-one 
• 50-89-5 thymidine 
• 1006597-31-4 2,3'-anhydro-2'-deoxy-5'-O-benzoyl-5-(E)-bromovinyluridine 
• 13030-62-1 3',5'-di-O-acetyl-2'-deoxyuridine 
• 1956-30-5 3',5'-O-diacetyl-5-iodo-2'-deoxyuridine 
• 85267-60-3 1-(3,5-di-O-acetyl-2-deoxy-β-D-erythro-pentofuranosyl)-5-(trimethylsilylethynyl)uracil 
• 139546-04-6 5-(1-hydroxy-2-bromoethyl)-3',5'-di-O-acetyl-2'-deoxyuridine 
• 84574-82-3 5-vinyl-3',5'-di-O-acetyl-2'-deoxyuridine 
• 86163-17-9 methyl (E)-3-(1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acrylate 
• 54-42-2 5-Iodo-2'-deoxyuridine 
• 73446-72-7 2,4-bis-O-(trimethylsilyl)-(E)-5-(2-bromovinyl)uracil 
• 57412-59-6 (E)-5-(2-carboxyvinyl)uracil 

Downstream Products

• 91593-18-9 3',5'-di-O-acetyl-(E)-5-(2-bromovinyl)-2'-deoxyuridine 
• 86214-06-4 (E)-5-(2-bromovinyl)-2'-deoxy-3-methyluridine 
• 232925-18-7 (E)-5-(2-bromovinyl)-2'-deoxy-5'-uridyl phenyl L-methoxyalaninylphosphoramidate 
• 80860-82-8 (E)-5-(2-bromovinyl)-2'-deoxyuridine 5'-monophosphate 
• 1006597-61-0 5'-O-(N-t-butyloxycarbonyl-ε-aminocaproyl)-2'-deoxy-5-(E)-bromovinyluridine 
• 1006597-62-1 3'-O-(N-t-butyloxycarbonyl-ε-aminocaproyl)-2'-deoxy-5-(E)-bromovinyluridine 
• 1006597-31-4 2,3'-anhydro-2'-deoxy-5'-O-benzoyl-5-(E)-bromovinyluridine 
• 87531-00-8 5'-O-benzoyl-1-(2'-deoxy-β-D-threo-pentofuranosyl)-5-(E)-(2-bromovinyl)-2,4(1H, 3H)-pyrimidinedione 
• 87531-01-9 5'-O-(4,4'-dimethoxytrityl)-2'-deoxy-5-(E)-bromovinyluridine 
• 114494-94-9 (E)-5-(2-bromovinyl)-2'-deoxy-5'-O-t-butyldiphenylsilyluridine 
• 84218-85-9 (E)-5-(2-bromovinyl)-2'-deoxy-5'-O-p-toluenesulphonyluridine 
• 111160-31-7 (E)-5-(2-bromovinyl)-1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-methyl-4-(1,2,4-triazol-1-yl)pyrimidin-2(1H)-one 

Relevant academic research and scientific papers

Syntheses of 5-(2-radiohaloethyl)- and 5-(2-radiohalovinyl)-2′-deoxyuridines. Novel types of radiotracer for monitoring cancer gene therapy with PET

Syntheses of 5-(2-[18F]fluoroethyl)- (1) 5-(2-[80Br] bromoethyl), (2), undeprotected (E)-5-(2-[18F]fluorovinyl)- (3) and (E)-5-(2-[80Br]bromovinyl),2′-deoxyuridines (4) as the tracers for monitoring cancer gene therapy with positron emission tomography were described. Decay corrected radiochemical yield and synthesis time including labeling and HPLC purification from end of bombardment for 1 was 9.5% and 2 hours, respectively; yield and time for 2 was 16% and 2 hours, respectively. Chemical (approximate to radiochemical) yield and time for synthesis of 3 was 7.5% and 7 minutes, respectively. Radiochemical yield and synthesis time including labeling and HPLC purification of an analytical sample of 4 was 60% and 30 minutes, respectively. Both 2 and 4 received the side reactions during HPLC purification, i.e. ring closure and cleavage of glycosidic bond, respectively. Application of 2 and 4 needed to be confirmed by in vitro or in vivo experiments. Radiochemical yield of 1 could be optimized by employing a modified protocol for preparation of its precursor. The preparation of fluorovinyl counterparts had demonstrated the potential utility of the stannane, 3-tolyl-3′,5′-di-O-acetyl-(E)-5-(2-stannylvinyl)- 2′-deoxyuridine 7. Copyright

Pd-imidate complexes as recyclable catalysts for the synthesis of C5-alkenylated pyrimidine nucleosides via Heck cross-coupling reaction

Pd-imidate complexes have been employed as efficient catalysts for the Heck alkenylation of unprotected 5-iodo-2′-deoxyuridine in acetonitrile. The protocol was also shown to work well for the unprotected 5-iodo-2′-deoxycytidine. A highly efficient scale-up synthesis of the HSV-1 inhibitor Brivudine (BVDU) is also accomplished in an overall yield of 72% over 3-steps. The catalyst also showed recyclability for 3 consecutive runs.

Novel synthesis process of bromovudine and bromovudine

The invention discloses a novel synthesis process of bromovudine and bromovudine, which comprises the following steps: taking beta-thymidine as an initial raw material, carrying out a formylation reaction on beta-thymidine and DMF-DMA to generate an intermediate I, heating the intermediate I and acetic acid to form a ring to generate an intermediate II, and reacting the intermediate II with hydrobromic acid to obtain the bromovudine. The novel synthesis process of bromovudine comprises the following steps: firstly, carrying out formylation reaction on beta-thymidine and DMF-DMA, then heating with acetic acid to form a ring, and finally, carrying out ring opening reaction with hydrobromic acid to obtain the bromovudine. The beta-thymidine is used as the starting material, the starting material is low in price and easy to obtain, expensive palladium does not need to be used as a catalyst, and the raw material cost of bromovudine can be effectively reduced. The synthetic route of the bromovudine is short, the conditions are mild, the operation is convenient, and the method is suitable for industrial production.

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.

A comparison between immobilized pyrimidine nucleoside phosphorylase from Bacillus subtilis and thymidine phosphorylase from Escherichia coli in the synthesis of 5-substituted pyrimidine 2′-deoxyribonucleosides

Pyrimidine nucleoside phosphorylase from Bacillus subtilis (BsPyNP, E.C. 2.4.2.3) and thymidine phosphorylase from Escherichia coli (EcTP, E.C. 2.4.2.4) were used, as immobilized enzymes, in the synthesis of 5-halogenated pyrimidine 2′-deoxyribonucleosides (14-18) by transglycosylation in fully aqueous medium. From the comparative study of the two biocatalysts, no remarkable differences emerged about their substrate specificity, bioconversion yield, stability in organic cosolvents (DMF and MeCN). Moreover, both biocatalysts could be recycled for at least 5 times with no loss of the productivity. Both enzymes do not accept arabinonucleosides and 2′,3′- dideoxynucleosides as substrates, whereas they catalyze bioconversions involving 5′-deoxyribonucleosides and 5-halogenated uracils. The synthesis of compounds 14-18 proceeded at a similar conversion (33-68% for BsPyNP and 25-62% for EcTP, respectively). Immobilization was found to exert, for both the biocatalysts, a dramatic enhancement of stability upon incubation in MeCN. Optimization of 5-fluoro-2′-deoxyuridine (14) synthesis (pH 7.5, 10 mM phosphate buffer, nucleoside/nucleobase 3:1 molar ratio) and subsequent scale-up afforded the target compound in 73% (EcTP) or 76% (BsPyNP) conversion (about 9 g/L).

Hydrogermylation of 5-ethynyluracil nucleosides: Formation of 5-(2-germylvinyl)uracil and 5-(2-germylacetyl)uracil nucleosides

A stereoselective radical-mediated hydrogermylation of the protected 5-ethynyluracil nucleosides with trialkyl-, triaryl,- or tris(trimethylsilyl) germanes gave (Z)-5-(2-germylvinyl)uridine, 2′-deoxyuridine, or ara-uridine as major products. Reaction of the β-triphenylgermyl vinyl radical intermediate with oxygen and fragmentation of the resulting peroxyradical provided also 5-[2-(triphenylgermyl)acetyl]pyrimidine nucleosides in low to moderate yields. Thermal isomerization of the latter in MeOH occurred via a four-centered activated complex, and subsequent hydrolysis of the resulting O-germyl substituted enol yielded 5-acetyluracil nucleosides in quantitative yield.

NUCLEOSIDES FOR SUPPRESSING OR REDUCING THE DEVELOPMENT OF RESISTANCE IN CYTOSTATIC THERAPY

The invention relates to special nucleosides, for example, a nucleoside of the formula I, wherein R1-R5 are as described herein, and also to drugs which contain these nucleosides. Furthermore, the invention relates to the use of such nucleosides in a method for suppressing or reducing the formation of resistance in the case of cytostatic treatment of a cancer patient.

Synthesis of nucleoside-based antiviral drugs in ionic liquids

Nucleoside-based antiviral drugs have been synthesized using imidazolium-based ionic liquids as reaction medium. The ionic liquids were proved to be better solvents for all the nucleoside in terms of solubility and reaction medium as compared to conventional molecular solvents.

Synthesis and in vitro anti-mycobacterial activity of 5-substituted pyrimidine nucleosides

Mycobacterium tuberculosis and Mycobacterium avium infections cause the two most important mycobacterioses, leading to increased mortality in patients with AIDS. Various 5-substituted 2′-deoxyuridines, uridines, 2′-O-methyluridine, 2′-ribofluoro-2′-deoxyuridines, 3′-substituted-2′,3′-dideoxy uridines, 2′,3′- dideoxyuridines, and 2′,3′-didehydro-2′,3′- dideoxyuridines were synthesized and evaluated for their in vitro inhibitory activity against M. bovis and M. avium. 5-(C-1 Substituted)-2′- deoxyuridine derivatives emerged as potent inhibitors of M. avium (MIC 90 = 1-5 μg/mL range). The nature of C-5 substituents in the 2′-deoxyuridine series appeared to be a determinant of anti-mycobacterial activity. This new class of inhibitors could serve as useful compounds for the design and study of new anti-tuberculosis agents.

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.