2565-47-1

Usage

Uses

Used in Pharmaceutical Industry:
N-METHYLBARBITURIC ACID is used as an impurity in the production of Trelagliptin (Zafatek) for the treatment of type 2 diabetes. Trelagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that helps regulate blood sugar levels in patients with type 2 diabetes by increasing the levels of insulin and decreasing the levels of glucagon.
As an impurity, N-METHYLBARBITURIC ACID may have potential effects on the safety, efficacy, and quality of the final drug product. Therefore, it is essential to monitor and control the levels of this impurity during the manufacturing process to ensure the drug meets the required standards and specifications.

InChI:InChI=1/C5H6N2O3/c1-7-4(9)2-3(8)6-5(7)10/h2H2,1H3,(H,6,8,10)

Upstream product

• 89284-14-0 5,5-dibromo-1-methyl-barbituric acid 
• 141-82-2 malonic acid 
• 108-24-7 acetic anhydride 
• 598-50-5 N-Methylurea 
• 105-53-3 diethyl malonate 
• 36161-39-4 1-methyl-6-methoxy-2,4-dioxo-1,2,3,4-tetrahydropyrimidine 
• 30914-82-0 3-methyl-6-chloro-3,4-dihydro-2H-1,3-oxazine-2,4-dione 
• 7647-01-0 hydrogenchloride 
• 2434-53-9 6-amino-1-methyluracil 
• 6972-82-3 5,6-diamino-1-methyluracil 
• 108-59-8 malonic acid dimethyl ester 
• 623-59-6 N-acetyl-N'-methylurea 

Downstream Products

• 98655-72-2 1-methyl-5-(2-phenyl-chromen-4-ylidene)-pyrimidine-2,4,6-trione 
• 27425-10-1 3-methyl-7-phenyl-1,5-dihydro-pyrano[2,3-d]pyrimidine-2,4-dione 
• 27425-23-6 6-bromo-3-methyl-7-phenyl-1,5-dihydro-pyrano[2,3-d]pyrimidine-2,4-dione 
• 98-98-6 2-Picolinic acid 
• 91974-07-1 5-benzoyl-1-methylpyrimidine-2,4,6-trione 
• 6702-71-2 6-(cyclohexylamino)-3-methyluracil 
• 5759-79-5 3-methyl-6-(benzylamino)uracil 
• 5770-20-7 6-benzylamino-1-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dione 
• 2850-37-5 8-Phenyl-1-methylxanthine 
• 1207174-46-6 3,6-dimethyl-1-phenyl-4-thien-2-yl-1H-pyrazolo-[4',3':5,6]pyrido[2,3-d]pyrimidine-5,7(6H,8H)-dione 
• 1207174-49-9 4-(1,3-benzodioxol-5-yl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[4',3':5,6]pyrido[2,3-d]pyrimidine-5,7(6H,8H)-dione 
• 1207174-40-0 4-(4-fluorophenyl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[4',3':5,6]pyrido[2,3-d]pyrimidine-5,7(6H,8H)-dione 
• 1207174-41-1 4-(4-chlorophenyl)-3,6-dimethyl-1-phenyl-1H-pyrazolo-[4',3':5,6]pyrido[2,3-d]pyrimidine-5,7(6H,8H)-dione 
• 1207174-45-5 3,6-dimethyl-4-(3-nitrophenyl)-1-phenyl-1H-pyrazolo-[4',3':5,6]pyrido[2,3-d]pyrimidine-5,7(6H,8H)-dione 

Relevant academic research and scientific papers

Convenient synthesis of toxoflavin that targets β-catenin/TCF4 signaling activities

A rapid and improved route for synthesis of toxoflavin, an antibiotic and antitumor agent, is described. The method uses easily obtained materials and simple and practical reactions, including chlorination, condensation, and diazotization to produce toxoflavin in five steps with 14.2% yield and 98.6% purity (HPLC). This synthetic toxoflavin effectively inhibited β-catenin/Tcf4 driven TOP-luciferase activity with an IC50 of less than 0.5 μM and induced colon cancer cell death in a dose-dependent manner with an IC50 of 0.29 μM.

Deazaflavins as mediators in light-driven cytochrome P450 catalyzed hydroxylations

A light-driven deazaflavin-dependent direct enzyme regeneration system has been developed for a P450-BM3 catalyzed CH-activating hydroxylation, thereby avoiding the need for the expensive NADPH cofactor. The Royal Society of Chemistry 2009.

Robust Photocatalytic Method Using Ethylene-Bridged Flavinium Salts for the Aerobic Oxidation of Unactivated Benzylic Substrates

7,8-Dimethoxy-3-methyl-1,10-ethylenealloxazinium chloride (1a) was found to be a superior photooxidation catalyst among substituted ethylene-bridged flavinium salts (R=7,8-diMeO, 7,8-OCH2O-, 7,8-diMe, H, 7,8-diCl, 7-CF3 and 8-CF3). Selection was carried out based on structure vs catalytic activity and properties relationship investigations. Flavinium salt 1a proved to be robust enough for practical applications in benzylic oxidations/oxygenations, which was demonstrated using a series of substrates with high oxidation potential, i. e., 1-phenylethanol, ethylbenzene, diphenylmethane and diphenylmethanol derivatives substituted with electron-withdrawing groups (Cl or CF3). The unique capabilities of 1a can be attributed to its high photostability and participation via a relatively long-lived singlet excited state, which was confirmed using spectroscopic studies, electrochemical measurements and TD-DFT calculations. This allows the maximum use of the oxidation power of 1a, which is given by its singlet excited state reduction potential of +2.4 V. 7,8-Dichloro-3-methyl-1,10-ethylenealloxazinium chloride (1 h) can be used as an alternative photocatalyst for even more difficult substrates. (Figure presented.).

NOVEL CRYSTAL FORM OF PRODUCTION INTERMEDIATE OF ALOGLIPTIN BENZOATE

PROBLEM TO BE SOLVED: To provide a method capable of industrially producing an important synthetic intermediate compound in the production of alogliptin benzoate. SOLUTION: There are provided: a crystal of a sodium salt of 1-methyl-2,4,6(1H,3H,5H)-pyrimidine trione having characteristic peaks at a diffraction angle (2θ) of 8.8±0.2°, 13.4±0.2° and 14.6±0.2° in powder X-ray diffraction: and a method for producing a crystal of a sodium salt of 1-methyl-2,4,6(1H,3H,5H)-pyrimidine trione which comprises reacting 1-methyl urea and dimethyl malonate in a methanol solvent in the presence of sodium methoxide. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2020,JPOandINPIT

A curved geleg sandbank preparation method

The invention claims a curved geleg sandbank preparation method, using methyl urea and malonic acid diethyl ester as an initial raw material for preparing 3 - methyl - 6 - chloro uracil, while at the same time by the 2 - hydroxymethyl - 4 - pentachloro as initial material to prepare 2 - chloromethyl - 4 - pentachloro, then the 3 - methyl - 6 - chloro uracil with 2 - chloromethyl - 4 - pentachloro prepared tune geleg sandbank, the material cost is low, the preparation process is easy to control, convenient for industrial production.

Synthesis method of 6-chloro-3-alkyl uracil

The invention relates to a synthesis method of 6-chloro-3-alkyl uracil, which is characterized by comprising the following steps: by using malonic acid and N-alkyl urea as raw materials, carrying outthe cyclization reaction to generate alkyl tripyrimidone; and then carrying out chlorination on the alkyl tripyrimidone to generate the 6-chloro-3-alkyl uracil. Compared with an existing method, the method is mild in reaction and low in cost, high-cost and high-risk raw materials such as high-toxicity and high-boiling phosphorus oxychloride are not used, and industrial large-scale production is facilitated; meanwhile, the chemical purity obtained by the method is high, the yield is good, and the economic benefit is good.

Preparation method for trelagliptin

The invention discloses a preparation method for trelagliptin and belongs to the field of organic synthesis. The preparation method comprises the following steps: (1) taking methylurea and diethyl malonate as initial raw materials and performing cyclization and chlorination reaction, thereby acquiring 3-methyl-6-chlorouracil; (2) acquiring 2-(6-chlorine-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-methyl)-4-fluorobenzonitrile from the nucleophilic substitution reaction of 3-methyl-6-chlorouracil and 2-bromine methyl-4-fluorobenzonitrile; (3) generating a target compound (R)-2-((6-(3-aminopiperidines-1-group)-3-methyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-group) methyl-4-fluorobenzonitrile (trelagliptin) through the reaction of 2-(6-chlorine-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-methyl)-4-fluorobenzonitrile and (R)-3-aminopiperidine. The preparation method has the characteristics of low-cost and easily acquired initial raw materials, convenient after-treatment, mild condition, operation convenience, and the like.

BICYCLIC-PYRIMIDINEDIONE COMPOUNDS

The present invention provides novel bicyclic pyrimidinedione compounds that are useful for the treatment of hypertrophic cardiomyopathy (HCM) and conditions associated with left ventricular hypertrophy or diastolic dysfunction. The synthesis and characterization of the compounds is described, as well as methods for treating HCM and other forms of heart disease.

Synthesis of N-aryl and N-arylcarbamoylamino derivatives of 1,3-diazinane-5-carboxamide and their activity against glioblastoma LN-229 cell line

Six structural motifs based on the initial (lead) structure of merbarone were designed, prepared, and tested against the glioblastoma LN-229 cell line. Three different structural moieties were modified in the search for optimal glioblastoma activity: the 1,3-diazinane moiety, the aryl moiety, and the heteroatom linker. Calculated molecular descriptors such as lipophilicity (C log P), acidic strength (calculated pKa), and polar surface area (PSA) were used to design a diverse structural library of these compounds. From six different structural motifs and 136 compounds, a handful of examples with moderate (100 μg/ml), good (10 μg/ml) and excellent (1 μg/ml) glioblastoma activity were elucidated.

Synthesis and antifungal activity of substituted 2,4,6-pyrimidinetrione carbaldehyde hydrazones

Opportunistic fungal infections caused by the Candida spp. are the most common human fungal infections, often resulting in severe systemic infections - a significant cause of morbidity and mortality in at-risk populations. Azole antifungals remain the mainstay of antifungal treatment for candidiasis, however development of clinical resistance to azoles by Candida spp. limits the drugs' efficacy and highlights the need for discovery of novel therapeutics. Recently, it has been reported that simple hydrazone derivatives have the capability to potentiate antifungal activities in vitro. Similarly, pyrimidinetrione analogs have long been explored by medicinal chemists as potential therapeutics, with more recent focus being on the potential for pyrimidinetrione antimicrobial activity. In this work, we present the synthesis of a class of novel hydrazone-pyrimidinetrione analogs using novel synthetic procedures. In addition, structure-activity relationship studies focusing on fungal growth inhibition were also performed against two clinically significant fungal pathogens. A number of derivatives, including phenylhydrazones of 5-acylpyrimidinetrione exhibited potent growth inhibition at or below 10 μM with minimal mammalian cell toxicity. In addition, in vitro studies aimed at defining the mechanism of action of the most active analogs provide preliminary evidence that these compound decrease energy production and fungal cell respiration, making this class of analogs promising novel therapies, as they target pathways not targeted by currently available antifungals.