41862-09-3

Usage

Uses

Used in Pharmaceutical Industry:
6-AMINO-1-ETHYL-1H-PYRIMIDINE-2,4-DIONE is used as an intermediate in the synthesis of new substituted xanthines for their high affinity and selectivity for the human adenosine A2B receptors. This makes it a valuable compound in the development of clinical candidates for the treatment of chronic inflammatory airway diseases.
Used in Chronic Inflammatory Airway Disease Treatment:
6-AMINO-1-ETHYL-1H-PYRIMIDINE-2,4-DIONE is used as a key component in the development of therapeutic agents for chronic inflammatory airway diseases. The synthesized xanthine derivatives targeting the adenosine A2B receptors can potentially alleviate symptoms and improve the quality of life for patients suffering from these conditions.

InChI:InChI=1/C6H9N3O2/c1-2-9-4(7)3-5(10)8-6(9)11/h3H,2,7H2,1H3,(H,8,10,11)

Upstream product

• 41078-06-2 2-cyano-N-(ethylcarbamoyl)acetamide 
• 625-52-5 N-Ethylurea 
• 372-09-8 cyanoacetic acid 
• 105-56-6 ethyl 2-cyanoacetate 

Downstream Products

• 752222-78-9 N'-(3-ethyl-1,2,3,6-tetrahydro-2,6-dioxopyrimidin-4-yl)-N,N-dimethylformamidine 
• 80798-51-2 6-amino-1-ethyl-5-nitrosopyrimidine-2,4(1H,3H)-dione 
• 63981-31-7 6-amino-1-ethyl-3-propylpyrimidine-2,4(1H,3H)-dione 
• 752222-79-0 6-amino-1-ethyl-5-nitroso-3-propylpyrimidine-2,4(1H,3H)-dione 
• 752222-81-4 5,6-diamino-1-ethyl-3-propylpyrimidine-2,4(1H,3H)-dione 
• 41078-01-7 3-Ethylxanthine 

Relevant academic research and scientific papers

Design, Synthesis, and Biological Evaluation of 8-Mercapto-3,7-Dihydro-1H-Purine-2,6-Diones as Potent Inhibitors of SIRT1, SIRT2, SIRT3, and SIRT5

Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases. They regulate many physiological processes and play important roles in inflammation, diabetes, cancers, and neurodegeneration diseases. Sirtuin inhibitors have potential applications in the treatment of neurodegenerative diseases and various cancers. Herein, we identified new sirtuin inhibitors based on the scaffold of 8-mercapto-3,7-dihydro-1H-purine-2,6-dione. To elucidate the inhibitory mechanism, the binding modes of the inhibitors in SIRT3 were established by molecular docking, showing that the inhibitors occupy the acetyl lysine binding site and interact with SIRT3, mainly through hydrophobic interactions. The interactions were validated by site-directed mutagenesis of SIRT3 and structure-activity relationship analysis of the inhibitors. Consistently, enzyme kinetic assays and microscale thermophoresis showed that these compounds are competitive inhibitors to the acetyl substrate, and mix-type inhibitors to NAD+. Furthermore, we demonstrated that the compounds are potent SIRT1/2/3/5 pan-inhibitors. This study provides novel hits for developing more potent sirtuin inhibitors.

Dihydropyridine Lactam Analogs Targeting BET Bromodomains

Inhibitors of Bromodomain and Extra Terminal (BET) proteins are investigated for various therapeutic indications, but selectivity for BRD2, BRD3, BRD4, BRDT and their respective tandem bromodomains BD1 and BD2 remains suboptimal. Here we report selectivity-focused structural modifications of previously reported dihydropyridine lactam 6 by changing linker length and linker type of the lactam side chain in efforts to engage the unique arginine 54 (R54) residue in BRDT-BD1 to achieve BRDT-selective affinity. We found that the analogs were highly selective for BET bromodomains, and generally more selective for the first (BD1) and second (BD2) bromodomains of BRD4 rather than for those of BRDT. Based on AlphaScreen and BromoScan results and on crystallographic data for analog 10 j, we concluded that the lack of selectivity for BRDT is most likely due to the high flexibility of the protein and the unfavorable trajectory of the lactam side chain that do not allow interaction with R54. A 15-fold preference for BD2 over BD1 in BRDT was observed for analogs 10 h and 10 m, which was supported by protein-based 19F NMR experiments with a BRDT tandem bromodomain protein construct.

SUBSTITUTED XANTHINE DERIVATIVES

The present invention relates to compounds of formula (I) a process for their manufacture, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment of conditions having an association with TRPC5 containing ion ch

SUBSTITUTED XANTHINE DERIVATIVES

The present invention relates to compounds of formula (I) a process for their manufacture, pharmaceutical compositions containing them and their use in therapy, particularly in the treatment of conditions having an association with TRPC5 containing ion channels. R1, R2, R3, R4 and R5 have meanings given in the description.

Designing an eEF2K-Targeting PROTAC small molecule that induces apoptosis in MDA-MB-231 cells

Eukaryotic elongation factor 2 kinase (eEF2K) is a key α-kinase that negatively regulates the extension step of protein synthesis, which consumes most of the energy and amino acids required for protein synthesis. Studies have found that eEF2K protein is related to the breast cancer. However, existing inhibitor effect has not achieved the desired effect in cancer therapy. Proteolysis target chimeric (PROTAC) technology is uses proteasome to degrade target protein to achieve the purpose of inhibiting tumour cell growth. Here, we reported that the use of PROTAC strategy in combining with star eEF2K inhibitor A484954 and its potential derivatives. Consequently, candidate compound 11l was found to degrade eEF2K and induce apoptosis in human breast carcinoma MDA-MB-231 cells. Together, these findings demonstrate that our eEF2K-targeting PROTAC small molecule would be a potential new strategy for future breast cancer therapy.

CAFFEINE INHIBITORS OF MTHFD2 AND USES THEREOF

The present invention provides compounds, compositions thereof, and methods of using the same.

Use of A2B Adenosine Receptor Antagonists for Treating Pulmonary Hypertension

This disclosure relates generally to treating patients having pulmonary hypertension, or symptoms associated therewith, by administering a therapeutically effective amount of an A2B receptor antagonist to the patient.

Approach to the library of fused pyridine-4-carboxylic acids by combes-type reaction of acyl pyruvates and electron-rich amino heterocycles

A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.

Selective, high affinity A2B adenosine receptor antagonists: N-1 monosubstituted 8-(pyrazol-4-yl)xanthines

A series of N-1 monosubstituted 8-pyrazolyl xanthines have been synthesized and evaluated for their affinity for the adenosine receptors (AdoRs). We have discovered two compounds 18 (CVT-7124) and 28 (CVT-6694) that display good affinity for the A2B AdoR (Ki = 6 nM and 7 nM, respectively) and greater selectivity for the human A1, A2A, and A3 AdoRs (>1000-, >830-, and >1500-fold; >850-, >700-, and >1280-fold, respectively). CVT-6694 has been shown to block the release of interleukin-6 and monocyte chemotactic protein-1 from bronchial smooth muscle cells (BSMC), a process believed to be promoted by activation of A2B AdoR.

Discovery of a novel A2B adenosine receptor antagonist as a clinical candidate for chronic inflammatory airway diseases

Recently, we have reported a series of new 1,3-symmetrically (R1 = R3) substituted xanthines (3 and 4) which have high affinity and selectivity for the human adenosine A2B receptors (hA 2B-AdoR). Unfortunately, this class of compounds had poor pharmacokinetic properties. This prompted us to investigate the effect of differential alkyl substitution at the N-1 and N-3 positions (N1-R ≠ N3-R) on A2B-AdoR affinity and selectivity; we had the dual objectives of enhancing affinity and selectivity for the A 2B-AdoR, as well as improving oral bioavailability. This effort has led to the discovery of compound 62, that displayed high affinity and selectivity for the hA2B-AdoR (Ki = 22 nM). In addition, compound 62 showed high functional potency in inhibiting the accumulation of cyclic adenosine monophosphate induced by 5′-N-ethylcarboxamidoadenosine in HEK-A2B-AdoR and NIH3T3 cells with KB values of 6 and 2 nM, respectively. In a single ascending-dose phase I clinical study, compound 62 had no serious adverse events and was well tolerated.