Month: October 2022

Yokoo, Hidetomo; Shibata, Norihito; Naganuma, Miyako; Murakami, Yuki; Fujii, Kiyonaga; Ito, Takahito; Aritake, Kosuke; Naito, Mikihiko; Demizu, Yosuke published the artcile< Development of a Hematopoietic Prostaglandin D Synthase-Degradation Inducer>, Quality Control of 89793-12-4, the main research area is prostaglandin D2 ubiquitin proteasome system protein knockdown PROTACs.

Although hematopoietic prostaglandin D synthase (H-PGDS) is an attractive target for treatment of a variety of diseases, including allergic diseases and Duchenne muscular dystrophy, no H-PGDS inhibitors have yet been approved for treatment of these diseases. Therefore, the development of novel agents having other modes of action to modulate the activity of H-PGDS is required. In this study, a chimeric small mol. that degrades H-PGDS via the ubiquitin-proteasome system, PROTAC(H-PGDS)-1(I), was developed. PROTAC(H-PGDS)-1 is composed of two ligands, TFC-007 (that binds to H-PGDS) and pomalidomide (that binds to cereblon). PROTAC(H-PGDS)-1 showed potent activity in the degradation of H-PGDS protein via the ubiquitin-proteasome system and in the suppression of prostaglandin D2 (PGD2) production Notably, PROTAC(H-PGDS)-1 showed sustained suppression of PGD2 production after the drug removal, whereas PGD2 production recovered following removal of TFC-007. Thus, the H-PGDS degrader-PROTAC(H-PGDS)-1-is expected to be useful in biol. research and clin. therapies.

ACS Medicinal Chemistry Letters published new progress about Allergy. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Quality Control of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Karimian, Azam; Karimi, Zahra published the artcile< Synthesis of A Novel Heterocyclic System of 3,8-Disubstituted-5H-Pyrimido[5',4':5,6][1,4]Thiazino[3,2-e][1,2,4]Triazine>, COA of Formula: C3H2BrN3O2, the main research area is chloro amino pyrimidothiazinotriazine preparation secondary amine nucleophilic substitution; pyrimidothiazinotriazinediyl diamine preparation.

The new compounds 6-methyl-8-morpholino-2H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2e][1,2,4]triazin-3(5H)-one and 6-methyl-8-(piperidin-1-yl)-2H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2-e][1,2,4]triazin-3(5H)-one were obtained from cyclocondensation of 6-bromo-1,2,4-triazine-3,5(2H,4H)-dione with appropriate 5-amino-6-methylpyrimidine-4-thiol in DMF and in the presence of potassium carbonate under reflux. Reaction of compounds with phosphorous oxychloride gave 4-(3-chloro-6-methyl-5H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2-e][1,2,4]triazin-8-yl)morpholine and 3-chloro-6-methyl-8-(piperidin-1-yl)-5H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2-e][1,2,4]triazine. Nucleophilic substitution of chlorine atom of compounds with typical secondary amines in DMF and K2CO3 produced the new derivatives of the 3,8-disubstituted-5H-pyrimido[5′,4′:5,6][1,4]thiazino[3,2-e][1,2,4]triazine ring systems . All the synthesized products were characterized and confirmed by their spectroscopic and microanal. data.

Polycyclic Aromatic Compounds published new progress about Fused heterocyclic compounds Role: SPN (Synthetic Preparation), PREP (Preparation). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, COA of Formula: C3H2BrN3O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Dudfield, Philip J.; Le, Van-Duc; Lindell, Stephen D.; Rees, Charles W. published the artcile< Synthesis of C-ribosyl imidazo[2,1-f ][1,2,4]triazines as inhibitors of adenosine and AMP deaminases>, Name: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione, the main research area is imidazotriazine C nucleoside preparation adenosine deaminase inhibitor; C ribosyl imidazotriazine preparation adenosine deaminase inhibition.

A 3-β-D-ribofuranoside of the new imidazo[2,1-f][1,2,4]triazine is isomeric and isoelectronic with the nucleoside deaminoformycin which is a good inhibitor of adenosine deaminase (ADA) while its 5′-monophosphate is a good inhibitor of AMP deaminase (AMPDA). The 6-methylsulfanyl derivative is synthesized by condensation of the monocyclic 1,2,4-triazine with a bromo aldehyde, which is accompanied by cyclization to give the protected C-nucleoside; the 8-methylsulfanyl group is removed by replacement by hydrazine and oxidation The 1,2,4-triazine cyclizes similarly with chloroacetaldehyde or its di-Me acetal to give 6,8-bis(methylsulfanyl)imidazo[2,1-f ][1,2,4]triazine, which is converted into the parent heterocycle by two routes, into mono- and di-substituted derivatives of the new ring system. 6-Methylsulfanyl-3-β-D-ribofuranosylimidazo[2,1-f][1,2,4]triazine is an inhibitor of mammalian ADA (IC50 40 μM).

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry published new progress about C-nucleosides Role: BAC (Biological Activity or Effector, Except Adverse), BSU (Biological Study, Unclassified), SPN (Synthetic Preparation), BIOL (Biological Study), PREP (Preparation). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Name: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yang, Jiao; Chen, Kai; Zhang, Guo; Yang, Qiu-Yuan; Li, Yue-Shan; Huang, Shen-Zhen; Wang, Yan-Lin; Yang, Wei; Jiang, Xiao-Juan; Yan, Heng-Xiu; Zhu, Jing-Qiang; Xiang, Rong; Luo, You-Fu; Li, Wei-Min; Wei, Yu-Quan; Li, Lin-Li; Yang, Sheng-Yong published the artcile< Structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of inhibitors of RET and its drug resistance mutants>, Recommanded Product: 4,6-Dichloro-5-methoxypyrimidine, the main research area is phenyldihydro pyrimido oxazinamine derivative preparation RET inhibitor cancer; Drug resistance mutant; Medullary thyroid cancer; RET kinase; Structure-activity relationship.

The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors. In this investigation, we report the structural optimization and structure-activity relationship studies of N-phenyl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of RET inhibitors. Among all the obtained kinase inhibitors, 1-(5-(tert-butyl)isoxazol-3-yl)-3-(4-((6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-yl)amino)phenyl)urea (17d) is a multi-kinase inhibitor and potently inhibits RET and its drug resistance mutants. It showed IC50 (half maximal inhibitory concentration) values of 0.010 μM, 0.015 μM, and 0.009 μM against RET-wild-type, RET-V804M, and RET-V804L, resp. 17d displayed significant anti-viability potencies against various RET-driving tumor cell lines. In a xenograft mouse model of NIH3T3-RET-C634Y, 17d exhibited potent in vivo anti-tumor activity, and no obvious toxicity was observed Mechanisms of action were also investigated by Western blot and immunohistochem. assays. Collectively, 17d could be a promising agent for the treatment of MTC, hence deserving a further investigation.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Recommanded Product: 4,6-Dichloro-5-methoxypyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Homma, Daiki; Taketani, Shuhei; Shirai, Takeshi; Caytan, Elsa; Roussel, Christian; Elguero, Jose; Alkorta, Ibon; Kitagawa, Osamu published the artcile< Rotational Behavior of N-(5-Substituted-pyrimidin-2-yl)anilines: Relayed Electronic Effect in Two N-Ar Bond Rotations>, Electric Literature of 89793-12-4, the main research area is rotational barrier Substituted pyrimidinyl anilines NMR DFT.

N-Methyl-2-methoxymethylanilines 1 bearing various 5-substituted-pyrimidin-2-yl groups were prepared, and their rotational behaviors were explored in detail. the rotational barriers around two N-Ar bonds increase in proportion to the electron-withdrawing ability of substituents X at the 5-position.

Journal of Organic Chemistry published new progress about Bond angle. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Electric Literature of 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Song, Jian; Cui, Xin-Xin; Wu, Bo-Wen; Li, Dong; Wang, Sheng-Hui; Shi, Lei; Zhu, Ting; Zhang, Yan-Bing; Zhang, Sai-Yang published the artcile< Discovery of 1,2,4-triazine-based derivatives as novel neddylation inhibitors and anticancer activity studies against gastric cancer MGC-803 cells>, Computed Properties of 4956-05-2, the main research area is neddylation triazine UBC12 NEDD8 conjugation antiproliferative anticancer activity; 1,2,4-Triazine; MGC-803; Neddylation; UBC12-NEDD8 conjugation.

Neddylation modification is often over-expressed in a variety of human tumor cells. Therefore, targeting neddylation pathway may represent a potential approach to the treatment of human tumors. Herein, we describe the discovery of a hit scaffold from our inhouse library and further structure-based optimizations. In this work, compound V11 could block the neddylation and inhibit the activity of NAE (with an EC50 value of 3.56μM), and a dose-dependent reduction of the Ubc12-NEDD8 conjugations was also observed Mol. docking results suggest compound V11 could bind tightly to NAE via hydrogen bonds and hydrophobic interactions. Compound V11 showed the best antiproliferative ability with an IC50 value of 8.22μM against gastric cancer MGC-803 cells. Further anticancer activity studies suggested that compound V11 inhibited MGC-803 cell growth, caused a cell cycle arrestment at G2/M phase and induced apoptosis via extrinsic and intrinsic apoptosis pathways. All the findings suggest that 1,2,4-triazine scaffold might provide a novel scaffold for the further development of neddylation inhibitors and compound V11 might be a potential neddylation inhibitor with anticancer activity.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Computed Properties of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bhonoah, Yunas published the artcile< 7-Azabicyclo[2.2.1]Heptanes in Natural Product Synthesis and Organocatalysis>, Name: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione, the main research area is azabicyclo heptane natural product synthesis organocatalysis.

There is no abstract available for this document.

Polyhedron published new progress about Catalysis. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Name: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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