2797-17-3

Usage

Uses

Used in Pharmaceutical Industry:
5-fluoro-1-[(2R,4R)-4-(hydroxymethyl)-7,7-dimethyl-3,6,8-trioxabicyclo[3.3.0]oct-2-yl]pyrimidine-2,4-dione is used as a pharmaceutical compound for its potential role in suppressing in vitro primary antibody response toward sheep red blood cells (SRBC). This property suggests its possible application in the development of drugs targeting immune response modulation.
Used in Chemical Research:
As a white solid with distinct chemical properties, 5-fluoro-1-[(2R,4R)-4-(hydroxymethyl)-7,7-dimethyl-3,6,8-trioxabicyclo[3.3.0]oct-2-yl]pyrimidine-2,4-dione can be utilized in chemical research for studying its reactivity, stability, and potential interactions with other molecules. This may lead to the discovery of new compounds or applications in various fields.
Used in Material Science:
The unique structure and properties of 5-fluoro-1-[(2R,4R)-4-(hydroxymethyl)-7,7-dimethyl-3,6,8-trioxabicyclo[3.3.0]oct-2-yl]pyrimidine-2,4-dione may also find applications in material science. It could be explored for its potential use in the development of new materials with specific characteristics, such as improved stability, reactivity, or other desirable properties.

InChI:InChI=1/C12H15FN2O6/c1-12(2)20-7-6(4-16)19-10(8(7)21-12)15-3-5(13)9(17)14-11(15)18/h3,6-8,10,16H,4H2,1-2H3,(H,14,17,18)/t6-,7?,8?,10-/m1/s1

Upstream product

• 362-43-6 2',3'-O-isopropylideneuridine 
• 316-46-1 5-fluorouridine 
• 77-76-9 2,2-dimethoxy-propane 
• 129141-66-8 2',3'-O-Isopropylidene-3-(4-methoxybenzyl)-5-fluorouridine 
• 4744-10-9 dimethoxypropane 
• 3868-21-1 2',3'-O-isopropylidene-O²,5'-cyclouridine 
• 1748-04-5 tribenzoyl uridine 
• 58-96-8 uridine 
• 4418-14-8 1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)-4-chloro-2(1H)-pyrimidinone 
• 67-64-1 acetone 

Downstream Products

• 129141-66-8 2',3'-O-Isopropylidene-3-(4-methoxybenzyl)-5-fluorouridine 
• 136386-45-3 3-benzyl-2',3'-O-isopropylidene-5-fluorouridine 
• 129141-69-1 5'-O-Cinnamoyl-2',3'-O-isopropylidene-5-fluorouridine 
• 82276-89-9 5-fluoro-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)uridine 
• 174638-15-4 (5-fluorouridine)-5'-phosphoric acid (3-dodecylthio-2-decyloxy)propyl ester 
• 82207-41-8 5'-O-tosyl-5-fluorouridine 
• 129141-78-2 5'-O-Cinnamoyl-5-fluorouridine 
• 129141-75-9 (E)-3-Phenyl-acrylic acid (2R,3S,4R,5R)-5-[5-fluoro-3-(4-methoxy-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester 
• 129141-72-6 (E)-3-Phenyl-acrylic acid (3aR,4R,6R,6aR)-6-[5-fluoro-3-(4-methoxy-benzyl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester 

Relevant academic research and scientific papers

Structure-activity relationships of orotidine-5′-monophosphate decarboxylase inhibitors as anticancer agents

A series of 6-substituted and 5-fluoro-6-substituted uridine derivatives were synthesized and evaluated for their potential as anticancer agents. The designed molecules were synthesized from either fully protected uridine or the corresponding 5-fluorourid

Synthesis and biological evaluation of 6-substituted-5-fluorouridine ProTides

A new family of thirteen phosphoramidate prodrugs (ProTides) of different 6-substituted-5-fluorouridine nucleoside analogues were synthesized and evaluated as potential anticancer agents. In addition, antiviral activity against Chikungunya (CHIKV) virus was evaluated using a cytopathic effect inhibition assay. Although a carboxypeptidase Y assay supported a putative mechanism of activation of ProTides built on 5-fluorouridine with such C6-modifications, the Hint docking studies revealed a compromised substrate-activity for the Hint phosphoramidase-type enzyme that is likely responsible for phosphoramidate bioactivation through P–N bond cleavage and free nucleoside 5′-monophosphate delivery. Our observations may support and explain to some extent the poor in vitro biological activity generally demonstrated by the series of 6-substituted-5-fluorouridine phosphoramidates (ProTides) and will be of guidance for the design of novel phosphoramidate prodrugs.

Nucleolipids of the cancerostatic 5-fluorouridine: Synthesis, adherence to oligonucleotides, and incorporation in artificial lipid bilayers

5-Fluorouridine (1a) was converted to its N(3)-farnesylated nucleoterpene derivative 8 by direct alkylation with farnesyl bromide (4). Reaction of the cancerostatic 1a with either acetone, heptan-4-one, nonadecan-10-one, or hentriacontan-16-one afforded the 2',3'-O-ketals 2a-2d. Compound 2b was then first farnesylated (→5) and subsequently phosphitylated to give the phosphoramidite 6. The ketal 2c was directly 5'-phosphitylated without farnesylation of the base to give the phosphoramidite 7. Moreover, the recently prepared cyclic 2',3'-O-ketal 11 was 5'-phosphitylated to yield the phosphoramidite 12. The 2',3'- O-isopropylidene derivative 2a proved to be too labile to be converted to a phosphoramidite. All novel derivatives of 1a were unequivocally characterized by NMR and UV spectroscopy and ESI mass spectrometry, as well as by elemental analyses. The lipophilicity of the phosphoramidite precursors were characterized by both their retention times in RP-18 HPLC and by calculated log P values. The phosphoramidites 6, 7, and 12 were exemplarily used for the preparation of four terminally lipophilized oligodeoxynucleotides carrying a cyanine-3 or a cyanine-5 residue at the 5'-(n-1) position (i.e., 14-17). Their incorporation in an artificial lipid bilayer was studied by single-molecule fluorescence spectroscopy and fluorescence microscopy.

CANCER THERAPY WITH MICROBUBBLES.

The invention relates to a microbubble-chemotherapeutic agent complex comprising a microbubble carrying a combination of chemotherapeutic agents for use in a method of treating cancer in a patient, wherein said combination of chemotherapeutic agents comprises: (a) a 5-fluoropyrimidine or a derivative thereof; (b) irinotecan or a derivative thereof; and (c) a platinum-based chemotherapeutic agent or a derivative thereof; and wherein said method comprises simultaneous, separate or sequential administration of folinic acid or a derivative thereof. The invention is particularly suitable for use in the treatment of deep-sited tumours and associated metastatic disease, for example in the treatment of pancreatic cancer. The invention further relates to the microbubble- chemotherapeutic agent complexes themselves, to methods for their preparation and to pharmaceutical compositions which contain them, optionally in combination with folinic acid or a folinic acid derivative.

Unified Total Synthesis of Polyoxins J, L, and Fluorinated Analogues on the Basis of Decarbonylative Radical Coupling Reactions

Polyoxins J (1 a) and L (1 b) are important nucleoside antibiotics. The complex and densely functionalized dipeptide structures of 1 a and 1 b contain thymine and uracil nucleobases, respectively. Herein we report the unified total synthesis of 1 a, 1 b, and their artificial analogues 1 c and 1 d with trifluorothymine and fluorouracil structures. Decarbonylative radical coupling between α-alkoxyacyl tellurides and a chiral glyoxylic oxime ether led to chemo- and stereoselective construction of the ribonucleoside α-amino acid structures of 1 a–d without damaging the preinstalled nucleobases. The high applicability of the radical-based methodology was further demonstrated by preparation of the trihydroxynorvaline moiety of 1 a–d. The two amino acid fragments were connected and elaborated into 1 a–d (longest linear sequence: 11 steps). Compounds 1 a and 1 b assembled in this way exhibited potent activity against true fungi, while only 1 d was active against Gram-positive bacteria.

Synthesis and structure-activity relationship of uracil nucleotide derivatives towards the identification of human P2Y6 receptor antagonists

P2Y6 receptor (P2Y6-R) is involved in various physiological and pathophysiological events. With a view to set rules for the design of UDP-based reversible P2Y6-R antagonists as potential drugs, we established structure-activity relationship of UDP analogues, bearing modifications at the uracil ring, ribose moiety, and the phosphate chain. For instance, C5-phenyl- or 3-NMe-uridine-5′-α,β-methylene-diphosphonate, 16 and 23, or lack of 2′-OH, in 12-15, resulted in loss of both agonist and antagonist activity toward hP2Y6-R. However, uridylyl phosphosulfate, 19, selectively inhibited hP2Y6-R (IC50 112 μM) versus P2Y2/4-Rs. In summary, we have established a comprehensive SAR for hP2Y6-R ligands towards the development of hP2Y6-R antagonists.

5-Fluoruoracil Derivatives

The present invention relates to a compound represented by formula (I) wherein X is selected from the group of formulae (II) to (IV) wherein R1 is H or C1-C50 chain which may be branched or linear and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and/or functional group(s)(G1); or R1 is a C3-C28 moiety which comprises at least one cyclic structure and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and functional group(s)(G1); R2 is H; or R2 is a Mono-phosphate, Di-phosphate, Tri-phosphate or phosphoramidite moiety; or R2 is -Y-X or -Y-L-Y1- X; Y and Y1 are independently from each other a single bond or a functional connecting moiety, X is a colloid-active compound (CA) or a fluorescence marker (FA) or a polynucleotide moiety having up to 50 nucleotide residues, preferably 10 to 25 nucleotides, especially a polynucleotide having an antisense or antigen effect; L is a linker by means of which Y and X are covalently linked together; R3 and R4 represent independently from each other a C1-C28-alkyl moiety which may optionally be substituted or interrupted by one or more heteroatom(s) and/or functional group(s);or R3 and R4 form a ring having at least 5 members, preferably a ring having 5 to 8 carbon atoms and wherein the ring may be substituted or interrupted by one or more hetero atom(s) and/or functional group(s); or R3 and R4 represent independently from each other a C1-C28-alkyl moiety substituted with one or more moieties selected from the group -Y-X or -Y-L-Y1-X; or R3 and R4 represent independently from each other -Y-X or -Y-L-Y1- X; R5 and R6 represent independently from each other a C1-C28-alkyl moiety which may optionally be substituted or interrupted by one or more heteroatom(s) and/or functional group(s); or R5 and R6 represent independently from each other a C1-C28-alkyl moiety substituted with one or more moieties selected from the group -Y-X or -Y-L-Y1-X; or R5 and R6 form a ring having at least 5 members, preferably a ring having 5 to 18 carbon atoms and wherein the ring may be substituted or interrupted by one or more hetero atom(s) and/or functional group(s); and/or one or more moieties selected from the group -Y-X or -Y-L-Y1- X; R5 and R6 represent independently from each other -Y-X or -Y-L-Y1- X; R7 is a hydrogen atom or -O-R8; R8 is H or C1-C28 chain which may be branched or linear and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and/or functional group(s)(G1); or R8 is -Y-X or -Y-L-Y1- X, with the proviso that R1 and R2 are not both H and/or with the proviso that the compound comprises at least two chains each of which having 4 or more carbon atoms.

Use of fosfluridine tidoxil (FT) for the treatment of intraepithelial proliferative diseases

The present invention is directed to the systemic administration of Fosfluridine Tidoxil, (5-fluorouridine)-5′-phosphoric acid (3-dodecylmercapto-2-decyloxy)propylester or a salt thereof, for the treatment of intraepithelial proliferative diseases such as actinic keratosis. The Fosfluridine Tidoxil can be systemically administered alone or in combination with topical treatment agents.

Compositions and methods for targeted enzymatic release of cell regulatory compounds

Novel pro-drugs and methods for their use to alter the growth and biological characteristics of living cells, tissues, or whole organisms are described. The methods allow for selective activation of the pro-drugs at or near transformant host cells expressing a gene for an enzyme that activates the pro-drugs. Pro-drugs according to a preferred embodiment of the invention are conjugates of a bioactive compound and a chemical group that is capable of being cleaved from the bioactive compound by action of an enzyme. Methods according to this invention include, (a) introducing into targeted cells a gene encoding an enzyme and (b) administering a pro-drug, wherein the enzyme releases the pro-drug from conjugation. In a preferred embodiment of the invention, the gene encoding the enzyme is a marker gene.

Prodrugs activated by targeted catalytic proteins

Prodrugs that are activated by and conjugated to a catalytic antibody conjugated to a moiety that binds to a tumor cell population are provided.