2240-25-7

Usage

Uses

Used in Pharmaceutical Industry:
6-AMINO-5-BROMOPYRIMIDIN-2(1H)-ONE is used as an active pharmaceutical ingredient for the development of anti-HIV agents due to its potent activity against the virus.
Used in Chemical Synthesis:
6-AMINO-5-BROMOPYRIMIDIN-2(1H)-ONE is used as a key intermediate in the synthesis of cross-link products, such as C[5-N6]A, C[5-2]A, C[5-8]A, A[2-5]C, and A[8-5]C, which have potential applications in various fields, including materials science and biology.

Purification Methods

5-Bromocytosine is recrystallised from H2O or 50% aqueous EtOH. Alternatively, dissolve ca 3g in conc HCl (10mL) and evaporate to dryness. Dissolve the residual hydrochloride in the minimum volume of warm H2O and make faintly alkaline with aqueous NH3. Collect the crystals and dry them in a vacuum at 100o. [Hilbdert & Jensen J Am Chem Soc 56 134 1934, Beilstein 25 III/IV 3689.]

InChI:InChI=1/C4H4BrN3O/c5-2-1-7-4(9)8-3(2)6/h1H,(H3,6,7,8,9)

Upstream product

• 71-30-7 6-amino-2-hydroxypyrimidine 
• 71-30-7 cytosine 
• 71-30-7 Cytosine 
• 148214-56-6 5-bromo-2-methoxypyrimidin-4-amine 

Downstream Products

• 6312-73-8 6-amino-5-bromo-2,4(1H,3H)-pyrimidinedione 
• 71-30-7 Cytosine 
• 1432446-11-1 C₁₂H₇BrClN₃O 
• 1220533-01-6 C₂₈H₂₈BrN₃O₅ 
• 255818-55-4 5-bromo-1-(5-O-benzoyl-2,3-dideoxy-2-fluoro-β-L-threo-pentofuranosyl)cytosine 
• 199486-81-2 N-1-(p-toluenesulfonyl)cytosine 
• 197452-35-0 1-(3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-β-L-erythro-pentofuranos-1-yl)-5-bromocytosine 
• 197452-36-1 1-(3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-α-L-erythro-pentofuranos-1-yl)-5-bromocytosine 

Relevant academic research and scientific papers

Synthesis of [2-14C,5-3H]cytosine and [2-14C,5-3H]uracil via bromination and catalytic bromine-tritium gas exchange

In micro-scale experiments, [2-14C,5-3H]cytosine and [2-14C,5-3H]uracil were synthesized via bromination and catalytic Br-3H exchange reaction with the use of [2-14C]cytosine and -uracil and tritium gas. The double labelling percentages of these products were 70 and 26, respectively. It was assumed that [2-14C,5-Br]uracil was subjected to reaction with hydrogen atom originally adsorbed on a palladium catalyst. This is to a lesser extent valid for [2-14C,5-Br]cytosine. The percentages of 3H labelling at 5 position of pyrimidine ring of cytosine and uracil were proved to be 96 and 73, respectively. For the analysis and purification of products, the HPLC eluting conditions using C18 reverse column and NaH2PO4 aqueous solution or H2O/methanol mixture as eluent were studied. Unreacted tritium gas was recovered with the use of adsorbents such as active charcoal and Zr-V-Fe getter.

Synthesis, structure and rearrangement of iodinated imidazo[1,2-c]pyrimidine-5(6H)-ones derived from cytosine

We describe mild and selective iodination of various 8-substituted imidazo[1,2-c]pyrimidine-5(6H)-ones (ethenocytosines). Starting ethenocytosines were obtained by cyclization of 5-halogenocytosines with chloroacetaldehyde or by subsequent Suzuki-Miyaura

Exploiting the 7-methylimidazo[1,5-a]pyrazin-8(7H)-one scaffold for the development of novel chemical inhibitors for Bromodomain and Extraterminal Domain (BET) family

The bromodomain and extraterminal (BET) family of proteins play a crucial role in promoting gene expression of critical oncogenes. Novel BET bromodomain inhibitors with excellent potency, drug metabolism and pharmacokinetics (DMPK) properties were in strong need for development. We reported a series of potential BET inhibitors through incorporation of imidazole into pyridine scaffold. Among them, a novel BET inhibitor with 7-methylimidazo[1,5-a]pyrazin-8(7H)-one core, compound 28, was considered to be the most promising for in-depth study. Compound 28 exhibited excellent BRD4-inhibitory activity with IC50 value of 33 nM and anti-proliferation potency with IC50 value of 110 nM in HL-60 (human promyelocytic leukemia) cancer cell lines. Western Blot indicated that compound 28 can effectively trigger apoptosis in BxPc3 cells by modulating the intrinsic apoptotic pathway. In conclusion, these results suggested that compound 28 has merely potential for leukemia treatment.

IMIDAZO[1,2-C]PYRIMIDINE DERIVATIVES AS PRC2 INHIBITORS FOR TREATING CANCER

Disclosed are compounds that inhibit Polycomb Repressive Complex 2 (PRC2) activity. In particular, disclosed are compounds of Formula (I) and pharmaceutical compositions thereof, and methods of using the compounds and pharmaceutical compositions in, for example, methods of treating cancer.

CYTOSINE-BASED TET ENZYME INHIBITORS

Provided herein, in some embodiments, are cytosine analogs, compositions comprising cytosine analogs, and methods of use for inhibiting a Ten-eleven translocation (TET) enzyme.

CYTOSINE-BASED TET ENZYME INHIBITORS

Provided herein, in some embodiments, are cytosine analogs, compositions comprising cytosine analogs, and methods of use for inhibiting a Ten-eleven translocation (TET) enzyme.

PRC2 INHIBITORS

The present invention relates to compounds that inhibit Polycomb Repressive Complex 2 (PRC2) activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention. (Formula (I))

Cytosine-Based TET Enzyme Inhibitors

DNA methylation is known as the prima donna epigenetic mark for its critical role in regulating local gene transcription. Changes in the landscape of DNA methylation across the genome occur during cellular transition, such as differentiation and altered neuronal plasticity, and become dysregulated in disease states such as cancer. The TET family of enzymes is known to be responsible for catalyzing the reverse process that is DNA demethylation by recognizing 5-methylcytosine and oxidizing the methyl group via an Fe(II)/alpha-ketoglutarate-dependent mechanism. Here, we describe the design, synthesis, and evaluation of novel cytosine-based TET enzyme inhibitors, a class of small molecule probes previously underdeveloped but broadly desired in the field of epigenetics. We identify a promising cytosine-based lead compound, Bobcat339, that has mid-μM inhibitor activity against TET1 and TET2, but does not inhibit the DNA methyltransferase, DNMT3a. In silico modeling of the TET enzyme active site is used to rationalize the activity of Bobcat339 and other cytosine-based inhibitors. These new molecular tools will be useful to the field of epigenetics and serve as a starting point for new therapeutics that target DNA methylation and gene transcription.

Dehalogenation of Halogenated Nucleobases and Nucleosides by Organoselenium Compounds

Halogenated nucleosides, such as 5-iodo-2′-deoxyuridine and 5-iodo-2′-deoxycytidine, are incorporated into the DNA of replicating cells to facilitate DNA single-strand breaks and intra- or interstrand crosslinks upon UV irradiation. In this work, it is shown that the naphthyl-based organoselenium compounds can mediate the dehalogenation of halogenated pyrimidine-based nucleosides, such as 5-X-2′-deoxyuridine and 5-X-2′-deoxycytidine (X=Br or I). The rate of deiodination was found to be significantly higher than that of the debromination for both nucleosides. Furthermore, the deiodination of iodo-cytidines was found to be faster than that of iodo-uridines. The initial rates of the deiodinations of 5-iodocytosine and 5-iodouracil indicated that the nature of the sugar moiety influences the kinetics of the deiodination. For both the nucleobases and nucleosides, the deiodination and debromination reactions follow a halogen-bond-mediated and addition/elimination pathway, respectively.

A 5-fluorocytosine preparation method

The invention discloses a preparation method of 5-flucytosine. The method comprises the following steps of: 1) cytosine and a halogenating reagent perform halogenating reaction in an organic solvent at 0-80 DEG C to prepare an intermediate (I), 2) the intermediate (I) reacts with an amino protecting agent at 0-120 DEG C to prepare an intermediate (II), and 3) the intermediate (II) and a fluoro reagent perform fluoro reaction in a polar aprotic solvent or hydrogen fluoride at 70-200 DEG C to prepare an intermediate (III), and the intermediate (III) directly performs amino deprotecting reaction, and is separated and purified to prepare 5-flucytosine. According to the method, a process route is reasonable, the product yield is high, the quality is good, the production safety of the fluoro reagent is high, and the method is simple to operate and suitable for industrial production.