Pyrimidines

Tzeng, Cherng Chyi; Motola, Nancy C.; Panzica, Raymond P. published the artcile< Synthesis of certain 5,6-diamino-as-triazines: precursors for fused heterocyclic systems>, Safety of 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione, the main research area is triazine diamino derivative; triazinedione amino thiation; thiation aminotriazinedione.

An improved synthesis of 6-amino-as-triazine-3,5-dione (I, X = X1 = O) and selective thiation of this heterocycle provides two key intermediates I (X = O, X1 = S; X = X1 = S). Methylation of I (X = O, X1 = S; X = X1 = S) under basic conditions leads to their methylthio analogs, which on treatment with methanolic NH3 furnish 5,6-diamino-as-triazin-3-one and 5,6-diamino-3-(methylthio)-as-triazine, resp., in good overall yield.

Journal of Organic Chemistry published new progress about 4956-05-2. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Safety of 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bruening, Fabian; Lovelle, Lucie E. published the artcile< Highly regioselective organocatalytic SNAr amination of 2,4-dichloropyrimidine and related heteroaryl chlorides>, Synthetic Route of 6554-61-6, the main research area is heteroaryl chloride cyclic amine amination; aminopyrimidine regioselective preparation.

A highly efficient and regioselective method for the SNAr amination of 2,4-dichloropyrimidine with oxazolidin-2-one and related weakly nucleophilic amines, using sodium sulfinate and tetrabutylammonium bromide as catalysts, is disclosed. This strategy facilitates the synthesis of various aminopyrimidines, e.g., I, in a regio- and chemoselective manner. This approach was successfully used for the amination of various activated N-heteroaromatic substrates.

European Journal of Organic Chemistry published new progress about Amination (SNAr). 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Synthetic Route of 6554-61-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Menova, Petra; Dvorakova, Hana; Eigner, Vaclav; Ludvik, Jiri; Cibulka, Radek published the artcile< Electron-Deficient Alloxazinium Salts: Efficient Organocatalysts of Mild and Chemoselective Sulfoxidations with Hydrogen Peroxide>, Name: Pyrimidine-2,4,5,6(1H,3H)-tetraone hydrate, the main research area is electron deficient alloxazinium salt organocatalyst Chemoselective Sulfoxidations LFER.

A series of substituted alloxazinium perchlorates has been prepared and tested as catalysts for the oxidation of sulfides to sulfoxides with hydrogen peroxide. The logarithms of the observed rate constants of thioanisole oxidation correlate with the Hammett σ constants of the substituents on the alloxazinium catalysts, as well as with their reduction potentials E0′ and their pKR+ values, representing the alloxazinium salt/pseudobase equilibrium The stronger the electron-withdrawing substituent, the more efficient is the alloxazinium catalyst. The alloxazinium salts with a cyano or trifluoromethyl group in position 8 proved to be the most efficient, operating at room temperature at small loadings, down to 0.1 mol,̂ achieving turnover number values of up to 640 and acceleration by a factor of 350 relative to the non-catalyzed oxidation The 8-cyanoalloxazinium perchlorate was evaluated as the best catalyst; however, due to its relatively good accessibility, the 8-(trifluoromethyl)alloxazinium perchlorate seems to be the catalyst of choice for sulfoxidations with hydrogen peroxide. It was successfully tested for the sulfoxidation of a series of aliphatic and aromatic sulfides on a preparative scale. It produced the corresponding sulfoxides in quant. conversions and with high isolated yields (87-98 %). No over-oxidation to sulfone was ever observed

Advanced Synthesis & Catalysis published new progress about Aromatic compounds, sulfoxides Role: SPN (Synthetic Preparation), PREP (Preparation). 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Name: Pyrimidine-2,4,5,6(1H,3H)-tetraone hydrate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Rabal, Obdulia; San Jose-Eneriz, Edurne; Agirre, Xabier; Sanchez-Arias, Juan Antonio; de Miguel, Irene; Ordonez, Raquel; Garate, Leire; Miranda, Estibaliz; Saez, Elena; Vilas-Zornoza, Amaia; Pineda-Lucena, Antonio; Estella, Ander; Zhang, Feifei; Wu, Wei; Xu, Musheng; Prosper, Felipe; Oyarzabal, Julen published the artcile< Design and Synthesis of Novel Epigenetic Inhibitors Targeting Histone Deacetylases, DNA Methyltransferase 1, and Lysine Methyltransferase G9a with In Vivo Efficacy in Multiple Myeloma>, Category: pyrimidines, the main research area is histone deacetylases DNA methyltransferase G9a inhibitors multiple myeloma antitumor.

Concomitant inhibition of key epigenetic pathways involved in silencing tumor suppressor genes has been recognized as a promising strategy for cancer therapy. Herein, we report a first-in-class series of quinoline-based analogs that simultaneously inhibit histone deacetylases (from a low nanomolar range) and DNA methyltransferase-1 (from a mid-nanomolar range, IC50 < 200 nM). Addnl., lysine methyltransferase G9a inhibitory activity is achieved (from a low nanomolar range) by introduction of a key lysine mimic group at the 7-position of the quinoline ring. The corresponding epigenetic functional cellular responses are observed: histone-3 acetylation, DNA hypomethylation, and decreased histone-3 methylation at lysine-9. These chem. probes, multi-target epigenetic inhibitors, were validated against the multiple myeloma cell line MM1.S, demonstrating promising in vitro activity of 12a (CM-444) with GI50 of 32 nM, an adequate therapeutic window (>1 log unit), and a suitable pharmacokinetic profile. In vivo, 12a achieved significant antitumor efficacy in a xenograft mouse model of human multiple myeloma.

Journal of Medicinal Chemistry published new progress about Acetylation (histone H3). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wang, Zhao; Kang, Dongwei; Feng, Da; Cherukupalli, Srinivasulu; Jiang, Xiangyi; Fu, Zhipeng; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng published the artcile< Targeting dual tolerant regions of binding pocket: Discovery of novel morpholine-substituted diarylpyrimidines as potent HIV-1 NNRTIs with significantly improved water solubility>, Formula: C6H2Cl2N2S, the main research area is morpholine diarylpyrimidine synthesis antiHIV NNRTI HIV1 CYP450; HIV-1; Morpholine; NNRTIs; SARs; Tolerant region I; Tolerant region II.

To address the intractable issues of drug resistance and poor solubility, a novel series of morpholine-substituted diarylpyrimidines targeting the tolerant region I and tolerant region II of NNIBP were rationally designed by utilizing the available crystallog. studies. The biol. evaluation results showed that four most promising compounds (14e1, 14g1, 14g2 and 14j2) displayed excellent potency against WT HIV-1 strain with EC50 values ranging from 58 to 87 nM, being far more potent than NVP and comparable to ETV. Besides, some derivatives exhibited moderate activity in inhibiting the mutant HIV-1 strains. More encouragingly, 14d2 (RF = 0.4) possessed higher antiresistance profile than ETV (RF = 6.3) and K-5a2 (RF = 3.0) toward the double mutant strain F227L + V106A. The HIV-1 RT inhibition assay confirmed their binding target. The mol. docking studies were conducted and discussed in detail to rationalize the preliminary SARs. Further test indicated that morpholine could indeed promote the improvement of water solubility Addnl., the in silico prediction of physicochem. properties and CYP enzymic inhibitory ability were investigated to evaluate their drug-like features.

European Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Formula: C6H2Cl2N2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wu, Tianxiao; Qin, Qiaohua; Liu, Nian; Zhang, Chu; Lv, Ruicheng; Yin, Wenbo; Sun, Yin; Sun, Yixiang; Wang, Ruifeng; Zhao, Dongmei; Cheng, Maosheng published the artcile< Rational drug design to explore the structure-activity relationship (SAR) of TRK inhibitors with 2,4-diaminopyrimidine scaffold>, SDS of cas: 18740-39-1, the main research area is diaminopyrimidine preparation tropomyosin receptor kinase inhibitor SAR mol docking; Anticancer; NTRK gene fusion; Pharmacophore model; TRK inhibitors.

Tropomyosin receptor kinase (TRK) is an ideal target for treating cancers caused by the NTRK gene fusion. In this study, more than 60 2,4-diaminopyrimidine derivatives were prepared to understand the structure-activity relationship and confirm the rationality of the pharmacophore model reported previously. Among them, compound I was found to be a potent pan-TRK inhibitor that inhibits the proliferation of Km-12 cell lines. Addnl., compound I induced the apoptosis of Km-12 cells in a concentration-dependent manner. Western blot anal. revealed that compound I inhibited the phosphorylation of TRK to block downstream pathways. Compound I also possessed outstanding plasma stability and liver microsomal stability in vitro, with half-lives greater than 289.1 min and 145 min, resp. Pharmacokinetic studies indicated that the oral bioavailability of compound I is 17.4%. These results demonstrate that compound I could serve as a novel lead compound for overcoming NTRK-fusion cancers.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, SDS of cas: 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mylari, Banavara L.; Miller, Max W.; Howes, Harold L. Jr.; Figdor, Sanford K.; Lynch, John E.; Koch, Richard C. published the artcile< Anticoccidial derivatives of 6-azauracil. 1. Enhancement of activity by benzylation of nitrogen-1. Observations on the design of nucleotide analogs in chemotherapy>, Related Products of 4956-05-2, the main research area is coccidiostat benzylazauracil derivative; azauracil derivative anticoccidial.

Of >100 6-azauracil derivatives prepared and tested against Eimeria tenella infections in Leghorn cockerels, the 1-benzyl derivatives were most active, with maximum activity shown by 1-benzyl derivatives with compact, electron-withdrawing substituents such as 3′- or 4′-fluorine, -chlorine, or -nitrile substituents. The most active compound was 1-(3-cyanobenzyl)-6-azauracil (I) [27414-41-1], with a potency ∼16 times that of 6-azauracil [461-89-2]. I was also effective against E. maxima, E. acervulina, E. brunetti, and E. necatrix. Metabolism experiments using C-14-labeled 1-benzyl-6-azauracil [5991-46-8] showed no cleavage of the side chain. Structure-activity relations are discussed.

Journal of Medicinal Chemistry published new progress about Coccidiosis. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Related Products of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mitran, Raul-Augustin; Boscornea, Aurelian Cristian; Stancu, Izabela-Cristina; Tomas, Stefan published the artcile< Some unusual spectral properties of 6-azauracil derivatives>, Formula: C3H2BrN3O2, the main research area is fluorescence spectrometry azauracil derivative.

The optical properties of several new 6-azauracil derivatives have been obtained by means of fluorescence spectroscopy. This method allowed a rapid and accurate characterization, having high specificity and sensitivity.

Scientific Bulletin – University “Politehnica” of Bucharest, Series B: Chemistry and Materials Science published new progress about 4956-05-2. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Formula: C3H2BrN3O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gershon, Herman; Parmegiani, Raulo published the artcile< Antifungal activity of ring poly-chlorinated pyrimidines: structure activity relations>, Formula: C4H2Cl2N2, the main research area is DRUG RESISTANCE, MICROBIAL; FUNGICIDES; PYRIMIDINES.

A total of 48 ring chlorinated pyrimidines were screened against strains of 5 fungi by the disk-plate method, liquid culture, and for activity of the vapors of the compounds Correlations of the results obtained by the 3 methods were made, and structure:activity relations were discussed. The outstanding members of this series were found to be 2,4,5-trichloropyrimidine, 4,5,6-trichloropyrimidine, and 2-chloro-methyl-4,5,6-trichloropyrimidine.

Applied Microbiology published new progress about 6554-61-6. 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Formula: C4H2Cl2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kandalkar, Sachin R.; Kaduskar, Rahul D.; Ramaiah, Parimi Atchuta; Barawkar, Dinesh A.; Bhuniya, Debnath; Deshpande, Anil M. published the artcile< Highly efficient one-pot amination of carboxylate-substituted nitrogen-containing heteroaryl chlorides via Staudinger reaction>, Related Products of 89793-12-4, the main research area is carboxylate substituted heteroaryl amine preparation; Staudinger reaction carboxylate substituted heteroaryl chloride.

An efficient one-pot method for the synthesis of tert-Bu 6-aminonicotinate I is described. The key transformation involves displacement of the chloro group in tert-Bu 6-chloronicotinate with azide followed by a Staudinger reaction. The scope of this methodol. is further extended for the synthesis of a series of carboxylate-substituted heteroaryl amines e. g., II. In particular, we synthesized tert-Bu carboxylate-substituted amino-pyridine, -pyridazine, and -pyrazine. In addition to one-pot conversion, short reaction time, simplicity of operation, ease of purification, and good yields are the key advantages of this methodol.

Tetrahedron Letters published new progress about Amination. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Related Products of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia