Month: October 2022

Li, Zhiqiang; Li, Xinzhi; Su, Ming-Bo; Gao, Li-Xin; Zhou, Yu-Bo; Yuan, Bingchuan; Lyu, Xilin; Yan, Ziqin; Hu, Chujiao; Zhang, Hao; Luo, Cheng; Chen, Zheng; Li, Jia; Zhao, Yujun published the artcile< Discovery of a Potent and Selective NF-κB-Inducing Kinase (NIK) Inhibitor That Has Anti-inflammatory Effects in Vitro and in Vivo>, Category: pyrimidines, the main research area is preparation NFkappaB inducing kinase inhibitor antiinflammatory toxic hepatitis; pyrrolopyrimidine amino preparation antiinflammatory hepatitis.

The overexpression of NIK plays a critical role in liver inflammatory diseases. Treatment of such diseases with small-mol. NIK inhibitors is a reasonable but underexplored approach. In this paper, we reported the discovery of a potent and selective NIK inhibitor I (XT2). The compound I inhibited the NIK kinase with an IC50 value of 9.1 nM in vitro, and it also potently suppressed NIK activities in intact cells. In isogenic primary hepatocytes, treatment with I efficiently suppressed the expressions of NIK-induced genes. The compound I was orally bioavailable in mice with moderate systemic exposure. In a NIK-associated mouse liver inflammation model, the compound I suppressed CCl4-induced upregulation of ALT, a key biomarker of acute liver injury, and also decreased immune cell infiltration into the injured liver tissue. Overall, these studies provide examples that an NIK inhibitor is able to suppress toxin-induced liver inflammations, which indicates its therapeutic potentials for the treatment of liver inflammatory diseases.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Thakur, Ashish; Tawa, Gregory J.; Henderson, Mark J.; Danchik, Carina; Liu, Suiyang; Shah, Pranav; Wang, Amy Q.; Dunn, Garrett; Kabir, Md.; Padilha, Elias C.; Xu, Xin; Simeonov, Anton; Kharbanda, Surender; Stone, Richard; Grewal, Gurmit published the artcile< Design, Synthesis, and Biological Evaluation of Quinazolin-4-one-Based Hydroxamic Acids as Dual PI3K/HDAC Inhibitors>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is quinazolinone hydroxamic acid dual PI3K HDAC inhibitor anticancer.

A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC50 < 10 nM) and selective against PI3Kγ, δ and HDAC6 enzymes and exhibited good antiproliferative activity against multiple cancer cell lines. The lead compound 48c, induced necrosis in several mutant and FLT3-resistant AML cell lines and primary blasts from AML patients, while showing no cytotoxicity against normal PBMCs, NIH3T3, and HEK293 cells. Target engagement of PI3Kδ and HDAC6 by 48c was demonstrated in MV411 cells using the cellular thermal shift assay (CETSA). Compound 48c showed good pharmacokinetics properties in mice via i.p. administration and provides a means to examine the biol. effects of inhibiting these two important enzymes with a single mol., either in vitro or in vivo. Journal of Medicinal Chemistry published new progress about Antitumor agents. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Safety of Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Dao, Pascal; Lietha, Daniel; Etheve-Quelquejeu, Melanie; Garbay, Christiane; Chen, Huixiong published the artcile< Synthesis of novel 1,2,4-triazine scaffold as FAK inhibitors with antitumor activity>, Reference of 4956-05-2, the main research area is arylamino chlorotriazine preparation antitumor agent FAK inhibitor; structure arylamino chlorotriazine inhibition FAK antitumor activity; mol docking calculation methoxymorpholinylphenylamino methylcarbamoylphenyl chlorotriazine; 1,2,4-Triazines; Anti-cancer activity; FAK inhibitors; Molecular docking; Synthesis.

Bis(arylamino)chloro-1,2,4-triazines I [R = 3,4,5-(MeO)3C6H2, 4-H2NCH2C6H4, 4-Cl-2-MeO-5-MeC6H2, 4-(4-morpholinyl)phenyl, 2-MeO-4-(4-morpholinyl)phenyl; R1 = 3-MeSO2NHC6H4, 2-MeNHCOC6H4] were prepared as inhibitors of focal adhesion kinase (FAK) for potential use as antitumor agents; their inhibition of FAK, of human cancer cells, and of tumorigenesis in cancer cells was determined I [R = 2-MeO-4-(4-morpholinyl)phenyl; R1 = 2-MeNHCOC6H4] inhibited FAK with an IC50 value of 230 nM and was toxic to cancer cells with IC50 values of 13 μM and 0.19 μM; colony formation in cancer cells was inhibited by I [R = 2-MeO-4-(4-morpholinyl)phenyl; R1 = 2-MeNHCOC6H4] with IC50 values of 1.5 μM and 1.0 μM. The structure of I [R = 2-MeO-4-(4-morpholinyl)phenyl; R1 = 2-MeNHCOC6H4] bound to FAK was determined by mol. docking calculations

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

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Takamatsu, Kayo; Takano, Atsushi; Yakushiji, Nobumasa; Morohashi, Kazunori; Morishita, Kenichi; Matsuura, Nobuyasu; Makishima, Makoto; Tai, Akihiro; Sasaki, Kenji; Kakuta, Hiroki published the artcile< The first potent subtype-selective retinoid X receptor (RXR) agonist possessing a 3-isopropoxy-4-isopropylphenylamino moiety, NEt-3IP (RXRα/β-dual agonist)>, Related Products of 89793-12-4, the main research area is isopropoxy isopropylphenylamino derivative preparation structure retinoid X receptor agonist.

Retinoid X receptor (RXR) agonists (rexinoids) are attracting much attention for their use in treatment of cancers, including tamoxifen-resistant breast cancer and taxol-resistant lung cancer, and metabolic disease. However, known RXR agonists have a highly lipophilic character. In addition, no subtype-selective RXR agonists have been found. The authors previously reported an RXRα-preferential agonist 4-[N-methanesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl) amino]benzoic acid. The RXR agonistic activity is much less than that of well-known RXR agonists. To develop potent, less-lipophilic, and subtype-selective RXR agonists, the authors created new RXR agonists possessing alkoxy and iso-Pr groups as a lipophilic domain of the common structure of well-known RXR agonists. As a result, compounds possessing branched alkoxy groups (I) and (II), showed RXR agonistic activity as potent as, or more potent than, the activities of representative RXR agonists. Moreover, I was the first RXRα/β-selective (or RXRα/β-dual) agonist. Being potent, less lipophilic, and having RXR subtype-selective activity, NEt-3IP I is expected to become a new drug candidate and to be a useful biol. tool for clarifying each RXR subtype function.

ChemMedChem published new progress about Retinoid X receptor α Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

O’Brien, Darrell E.; Springer, Robert H.; Cheng, C. C. published the artcile< New Mannich reaction of pyrimidines>, Safety of 5-Hydroxypyrimidin-4(3H)-one, the main research area is .

4,5-Dihydroxypyrimidines undergo the Mannich reaction with primary and secondary amines and CH2O at the 6-position. 5-Hydroxy-6-piperidinomethyluracil, 3,6-dimethyl-3,4-dihydro-2H-pyrimido[4,5-e]-1,3-oxazin-8-ol (I, R = Me), and the 6-OH analog of I were prepared in this manner. The new Mannich reaction appears to be a general method for the synthesis of compounds containing the new 3,4-dihydro-2H-pyrimido[4,5-e]-1,3-oxazine ring system.

Journal of Heterocyclic Chemistry published new progress about Mannich reaction. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Safety of 5-Hydroxypyrimidin-4(3H)-one.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Solberg, Jan; Undheim, Kjell published the artcile< Palladium catalysis in the preparation of alkynylpyrimidines>, Related Products of 99469-85-9, the main research area is iodopyrimidine alkyne coupling; palladium complex catalyst coupling; alkynylpyrimidine; pyrimidine alkynyl.

Coupling reaction of iodopyrimidines I (R = SMe, OSiMe3; R1 = iodo) with R2CCH (e.g., R2 = Ph, Bu) using Pd catalysts gave alkynylpyrimidines I (R1 = CCR2). Hydrolysis of I (R = OSiMe3, R1 = CCR2) with H2O at room temperature gave pyrimidinones II. m-ClC6H4C(O)OOH oxidn of I (R = SMe, R1 = CCR2) gave I (R = SO2Me). I (R = SO2Me, R1 = CCPh) on alk. hydrolysis gave II (R2 = Ph).

Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry published new progress about Coupling reaction. 99469-85-9 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2S, Related Products of 99469-85-9.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Mitran, Raul-Augustin; Draghici, Constantin; Tomas, Stefan published the artcile< New 6-azauracil derivatives>, Recommanded Product: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione, the main research area is aromatic amine bromoazauracil nucleophilic substitution; phenol bromoazauracil nucleophilic substitution; aryl azauracil preparation.

Six new 6-azauracil derivatives were obtained through the nucleophilic substitution of 5-bromo-6-azauracil with various aromatic amines and phenols. These compounds were characterized by means of UV-VIS, IR and 1H-NMR spectroscopy.

Revista de Chimie (Bucharest, Romania) published new progress about Aromatic amines Role: RCT (Reactant), RACT (Reactant or Reagent). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Recommanded Product: 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ouyang, Yao; Xu, Xiu-Hua; Qing, Feng-Ling published the artcile< Trifluoromethanesulfonic Anhydride as a Low-Cost and Versatile Trifluoromethylation Reagent>, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is fluoromethanesulfonic anhydride fluoromethylation reagent photoredox catalysis pyridine activation; photoredox catalysis; pyridine; radical; trifluoromethanesulfonic anhydride; trifluoromethylation.

A large number of reagents have been developed for the synthesis of trifluoromethylated compounds However, an ongoing challenge in trifluoromethylation reaction is the use of less expensive and practical trifluoromethyl sources. We report herein the unprecedented direct trifluoromethylation of (hetero)arenes using trifluoromethanesulfonic anhydride as a radical trifluoromethylation reagent by merging photoredox catalysis and pyridine activation. Furthermore, introduction of both the CF3 and OTf groups of the trifluoromethanesulfonic anhydride into internal alkynes to access tetrasubstituted trifluoromethylated alkenes was achieved. Since trifluoromethanesulfonic anhydride is a low-cost and abundant chem., this method provides a cost-efficient and practical route to trifluoromethylated compounds

Angewandte Chemie, International Edition published new progress about Alkynes, internal Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ishikawa, Fumiyoshi; Kosasayama, Akira; Yamaguchi, Hitoshi; Watanabe, Yoshifumi; Saegusa, Junji; Shibamura, Seiichi; Sakuma, Kyoko; Ashida, Shinichiro; Abiko, Yasushi published the artcile< Cyclic guanidines. 14. Imidazo[1,2-a]thienopyrimidin-2-one derivatives as blood platelet aggregation inhibitors>, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is cyclic guanidine; imidazothienopyrimidinone preparation blood platelet; thienopyrimidinone imidazo; pyrimidinone imidazothieno; structure blood platelet imidazothienopyrimidinone; reduction ethoxycarbonylmethylation amination dichlorothienopyrimidine.

A series of novel 1,2,3,5-tetrahydroimidazo[1,2-a]thieno[2,3-d]-, and -[3,4-dpyrimidin-2-one derivatives were prepared and tested for the activity of inhibiting platelet aggregation in rats in vitro and ex vivo. They were prepared by the following reactions: NaBH4 reduction of 2,4-dichlorothienopyrimidines, followed by ethoxycarbonylmethylation and successive amination. Most of the compounds were found to be potent inhibitors of blood platelet aggregation. Structure-activity relationships indicated the essential contribution of the lactam structure and lipophilic substituents on the thiophene ring to the effective interaction of the compounds with a receptor site on the platelet. Among the compounds studied, 1,2,3,5,6,7,8,9-octahydro[1]benzothieno[1,2-d]imidazo[1,2-a]pyrimidin-2-one exhibited the most favorable activity.

Journal of Medicinal Chemistry published new progress about Blood platelet. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ta-Shma, Rachel; Torres, Avital; Chevion, Mordechai; Breuer, Eli; Quntar, Abed Al Aziz; Enk, Claes D.; Srebnik, Morris published the artcile< An autoxidation study of C2 substituted pyrimidine amino reductones>, Safety of 5-Hydroxypyrimidin-4(3H)-one, the main research area is autoxidation pyrimidine amino reductone.

Three pyrimidine derivatives I (R = Me, H, SMe) , differing from isouramil(I; R = OH) and divicine (I; R = NH2) at C2, were synthesized and their autoxidation rates measured spectrophotometrically. The autoxidation rates of all five pyrimidines were correlated with σ p + values (rho = -1.28, r2 = 0.949).

Tetrahedron published new progress about Autoxidation. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Safety of 5-Hydroxypyrimidin-4(3H)-one.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia