Month: October 2022

Jung, Seung-Youn; Nam, Ky-Youb; Park, Jeong-In; Song, Kyung-Hee; Ahn, Jiyeon; Park, Jong Kuk; Um, Hong-Duck; Hwang, Sang-Gu; Choi, Sang Un; Song, Jie-Young published the artcile< Radiosensitizing effect of novel phenylpyrimidine derivatives on human lung cancer cells via cell cycle perturbation>, Product Details of C4H2Br2N2, the main research area is lung cancer cell phenylpyrimidine derivative radiosensitizing.

Radiotherapy is one of the most common treatments for cancer, but radioresistance and injury to normal tissue are considered major obstacles to successful radiotherapy. Thus, there is an urgent need to develop radiosensitizers to improve the therapeutic outcomes of radiotherapy in cancer patients. Our previous efforts to identify novel radiosensitizers, using high-throughput screening targeting p53 and Nrf2 revealed a promising N-phenylpyrimidin-2-amine (PPA) lead compound; 17 derivatives of this lead compound were examined in the present study. PPA5, 13, 14, 15, and 17 inhibited cell viability by more than 50% with a marked increase in the proportion of cells arrested at the G2/M phase of cell cycle. Among these compounds, PPA15 markedly increased the sub-G1 cell population and increased the levels of cyclin B1 and phosphorylation levels of cyclin-dependent kinases 1 (CDK1). Combined treatment with radiation and PPA14 or PPA15 significantly decreased clonogenic survival. An in vitro kinase assay revealed that PPA15 inhibited multiple CDKs involved in cell cycle regulation. Compared with drug or radiation treatment alone, combined treatment with PPA15 and radiation resulted in the suppression of A549 tumor growth in mice by 59.5% and 52.7%, resp. Treatment with PPA15 alone directly inhibited tumor growth by 25.7%. These findings suggest that the novel pan CDK inhibitor, PPA15, may be a promising treatment to improve the effectiveness of radiotherapy for the treatment of cancer.

Journal of Pharmacology and Experimental Therapeutics published new progress about Apoptosis. 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Product Details of C4H2Br2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Fang, Yuanying; Zhang, Shaokun; Li, Min; Xiong, Lijuan; Tu, Liangxing; Xie, Saisai; Jin, Yi; Liu, Yanhua; Yang, Zunhua; Liu, Ronghua published the artcile< Optimisation of novel 4, 8-disubstituted dihydropyrimido[5,4-b][1,4]oxazine derivatives as potent GPR 119 agonists>, Application of C5H4Cl2N2O, the main research area is dihydropyrimido oxazine derivative preparation GPR 119 agonist diabetes; GPR 119 agonists; Optimisation; pyrimidodihydrooxazine; type 2 diabetes mellitus.

GPR119 is a promising target for discovery of anti-type 2 diabetes mellitus agents. We described the optimization of a novel series of pyrimido[5,4-b][1,4]oxazine derivatives as GPR119 agonists. Most designed compounds exhibited good agonistic activities. Among them, compound and demonstrated the potent EC50 values (13 and 12 nM, resp.) and strong inherent activities. Moreover, significant hypoglycemic effect of compound was observed by reducing the blood glucose AUC0-2h at the dose of 30 mg/kg, which is stronger than Vildagliptin (23.4% reduction vs. 17.9% reduction).

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antidiabetic agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Application of C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Choi, Chulho; Nuhant, Philippe; Mousseau, James J.; Yang, Xiaojing; Gerstenberger, Brian S.; Williams, Jessica M.; Wright, Stephen W. published the artcile< Synthesis of Chiral Azabicycles from Pyroglutaminols>, Formula: C7H7ClN2O2, the main research area is chiral azabicycle morpholine piperazine derivative preparation; stereocontrolled intramol SN2 cyclization pyroglutaminol.

The stereocontrolled synthesis of a range of substituted bicyclic morpholine and piperazine derivatives is reported from substituted pyroglutaminols via an intramol. SN2 cyclization as the key step. This enantiospecific approach toward chiral bicyclic morpholines and piperazines offers new opportunities to access these challenging ring systems, which are becoming increasingly common motifs in drug discovery.

Organic Letters published new progress about Cyclization, stereoselective. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Formula: C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Zhang, Xuqing; Zhu, Bin; Sun, Weimei; Wang, Mina; Albarazanji, Kamal; Ghosh, Brahma; Cummings, Maxwell; Lenhard, James; Leonard, James; Macielag, Mark; Lanter, James published the artcile< Discovery of a novel series of guanidinebenzoates as gut-restricted enteropeptidase and trypsin dual inhibitors for the treatment of metabolic syndrome>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is guanidinebenzoates gutrestricted enteropeptidase trypsin dual inhibitor treatment metabolic syndrome; Enteropeptidase inhibitor; Guanidinebenzoate; Gut-restriction; Trypsin inhibitor.

Novel series of guanidinebenzoate enteropeptidase and trypsin dual inhibitors has been discovered and SAR studies were conducted. Optimization was focused on improving properties for gut restriction, including increased aqueous solubility, lower cellular permeability, and reduced oral bioavailability. Lead compounds were identified with efficacy in a mouse fecal protein excretion study.

Bioorganic & Medicinal Chemistry Letters published new progress about Biological permeation. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

McGee, Danny P. C.; Martin, John C.; Verheyden, Julien P. H. published the artcile< Synthesis of the 7-deaza and 5-aza-7-deaza purine analogs of the antiherpes agent 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG)>, Recommanded Product: 4-Methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine, the main research area is pyrrolopyrimidinone acyclic nucleoside analog; imidazotriazinone acyclic nucleoside analog; acyclic nucleoside pyrrolopyrimidinone imidazotriazinone; virucide acyclic nucleoside; DHPG analog; hydroxypyropoxymethylpyrrolopyrimidinone amino; hydroxypropoxymethylimidazotriazinone amino.

DHPG analogs I and II were prepared Reaction of 2-amino-4-methoxypyrrolo[2,3-d]pyrimidine with 1,3-dibenzyloxy-2-(chloromethyl)glycerol under phase-transfer conditions gave a product which on sequential treatment with p-MeC6H4SK (to cleave the Me ether) and BBr3 (for debenzylation) gave I. Reaction of 2-acetamidoimidazo[1,2-a]-s-triazin-4-one with 1,3-dibenzyloxy-2-(acetoxymetyl)glycerol gave a product, which on debenzylation (by catalytic transfer hydrogenation) and then deacetylation gave II. I and II were inactive against herpes simplex virus types I and II in cell culture.

Journal of Heterocyclic Chemistry published new progress about Antiviral agents. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Recommanded Product: 4-Methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sagong, Hye Yeon; Bauman, Joseph D.; Patel, Disha; Das, Kalyan; Arnold, Eddy; LaVoie, Edmond J. published the artcile< Phenyl Substituted 4-Hydroxypyridazin-3(2H)-ones and 5-Hydroxypyrimidin-4(3H)-ones: Inhibitors of Influenza A Endonuclease>, Application of C5H4Cl2N2O, the main research area is aryl hydroxypyridazinone preparation influenza A endonuclease inhibitor antiviral; hydroxypyrimidinone aryl preparation influenza A endonuclease inhibitor antiviral.

Seasonal and pandemic influenza outbreaks remain a major human health problem. Inhibition of the endonuclease activity of influenza RNA-dependent RNA polymerase is attractive for the development of new agents for the treatment of influenza infection. Authors’ earlier studies identified a series of 5- and 6-Ph substituted 3-hydroxypyridin-2(1H)-ones that were effective inhibitors of influenza endonuclease. These agents identified as bimetal chelating ligands binding to the active site of the enzyme. In the present study, several aza analogs of these Ph substituted 3-hydroxypyridin-2(1H)-one compounds were synthesized and evaluated for their ability to inhibit the endonuclease activity. In contrast to the 4-aza analog of 6-(4-fluorophenyl)-3-hydroxypyridin-2(1H)-one, the 5-aza analog (5-hydroxy-2-(4-fluorophenyl)pyrimidin-4(3H)-one) did exhibit significant activity as an endonuclease inhibitor. The 6-aza analog of 5-(4-fluorophenyl)-3-hydroxypyridin-2(1H)-one (6-(4-fluorophenyl)-4-hydroxypyridazin-3(2H)-one) also retained modest activity as an inhibitor. Several varied 6-phenyl-4-hydroxypyridazin-3(2H)-ones and 2-phenyl-5-hydroxypyrimidin-4(3H)-ones, e.g., I (X-rays crystal structure in complex with endonuclease shown), were synthesized and evaluated as endonuclease inhibitors. The SAR observed for these aza analogs are consistent with those previously observed with various Ph substituted 3-hydroxypyridin-2(1H)-ones.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Application of C5H4Cl2N2O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

John, Joyamma published the artcile< Evaluate the hypoglycemic effect of vinca rosea leaf extracts in alloxan induced diabetic rats>, HPLC of Formula: 2244-11-3, the main research area is allaxon induced diabetic Vinca rosea leaf extract hypoglycemic effect.

The present study was carried out to evaluate the antidiabetic activity of aqueous leaf extract of Vinca rosea. The aqueous extract at high dose (300mg/100g) body weight showed a significant hypoglycemic activity. Improvement in the body weight and water and food consumption is also observed after the treatment with herbal extract

International Journal of Science and Nature published new progress about Antidiabetic agents. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, HPLC of Formula: 2244-11-3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Wang, Ruifeng; Chen, Yixuan; Zhao, Xiangxin; Yu, Sijia; Yang, Bowen; Wu, Tianxiao; Guo, Jing; Hao, Chenzhou; Zhao, Dongmei; Cheng, Maosheng published the artcile< Design, synthesis and biological evaluation of novel 7H-pyrrolo[2,3-d]pyrimidine derivatives as potential FAK inhibitors and anticancer agents>, SDS of cas: 18740-39-1, the main research area is pyrrolopyrimidine aryl pyrazolyl piperidinylamino phosphine oxide preparation antitumor agent; focal adhesion kinase inhibitor phosphine oxide pyrrolopyrimidine derivative preparation; 7H-pyrrolo[2,3-d]pyrimidine; Anticancer; Dimethylphosphine oxide; FAK inhibitor; Molecular docking; Structure-activity relationship.

A series of 7H-pyrrolo[2,3-d]pyrimidine derivatives possessing a dimethylphosphine oxide moiety I (20a-i, R5, R6, R7 = H, R3 = acylamino, sulfamoyl, phosphonomethyl, carbamoyl, amino; 25a-h, R3 = 4-piperidinylaminocarbonyl, R5 = H, halo, alkoxy, CF3, R6 = H, Me, F, R7 = H, F) and II (22a-g, R4 = Me. CHF2CH2, MeOCH2CH2, tetrahydropyranyl, piperidinyl, CH2CONMe2) were designed, synthesized and evaluated as novel Focal adhesion kinase (FAK) inhibitors. Most compounds potently suppressed the enzymic activities of FAK, with IC50 values in the 10-8-10-9 M range, and potently inhibited the proliferation of breast (MDA-MB-231) and lung (A549) cancer cell lines. The representative compound 25b (R5 = OMe, R6 = R7 = H) exhibited potent enzyme inhibition (IC50 = 5.4 nM) and good selectivity when tested on a panel of 26 kinases. Compound 25b exhibited antiproliferative activity against A549 cells (IC50 = 3.2 μM) and relatively less cytotoxicity to a normal human cell line HK2. Compound 25b also induced apoptosis and suppressed the migration of A549 cells in a concentration-dependent manner. Further profiling of compound 25b revealed it had good metabolic stability in mouse, rat and human liver microsomes in vitro and showed weak inhibitory activity against various subtypes of human cytochrome P 450. The docking study of compound 25b was performed to elucidate its possible binding modes and to provide a structural basis for further structure-guided design of FAK inhibitors.

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

Xiong, Jian; Wang, Jingjing; Hu, Guoping; Zhao, Weili; Li, Jianqi published the artcile< Design, synthesis and biological evaluation of novel, orally bioavailable pyrimidine-fused heterocycles as influenza PB2 inhibitors>, Electric Literature of 18740-39-1, the main research area is pyrimidine fused heterocycle preparation; mol docking SAR influenza PB2 inhibitor; Drug design; Influenza; Metabolic stability; PB2; Polymerase inhibitor.

With the aim to identify novel influenza PB2 inhibitors with high potency and excellent pharmacokinetic parameters, two new series of pyrimidine-fused heterocycle derivs were designed and synthesized based on two generations of co-crystal structures. Docking studies with the newly disclosed PDB structure guided the second round of rational design and led to the discovery of 3-((2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)thieno[3,2-d]pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid, (2S,3S)-3-((2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)thieno[2,3-d]pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid and (2S,3S)-3-((2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid as representative compounds with improved potency (EC50 < 1 nM). After pinpointing the metabolic labile site, the C-N replacement of compound (2S,3S)-3-((2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid successfully produced compound (2S,3S)-3-((2-(5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-yl)-6,7-dihydrothieno[3,2-d]pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid, which demonstrated highly improved PK properties (Cl = 1.3 mL/min/kg, PO AUC = 152 μM h at 10 mpk in mouse, F = 57%) and improved potency, emerging as a promising lead compound for the treatment of influenza A infection. European Journal of Medicinal Chemistry published new progress about Antiviral agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Electric Literature of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Trenker, Stefan; Grunenberg, Lars; Banerjee, Tanmay; Savasci, Goekcen; Poller, Laura M.; Muggli, Katharina I. M.; Haase, Frederik; Ochsenfeld, Christian; Lotsch, Bettina V. published the artcile< A flavin-inspired covalent organic framework for photocatalytic alcohol oxidation>, Formula: C4H4N2O5, the main research area is diethyl bis formylphenyl alloxazine covalent organic framework preparation; aryl aldehyde preparation; alc oxidation catalyst FEAx COF.

Herein, the construction and use of a novel COF (FEAx-COF) photocatalyst, inspired by natural flavin cofactors was reported. The functionality of the alloxazine chromophore incorporated into the COF backbone was retained and study the effects of this heterogenization approach by comparison with similar mol. photocatalysts. The integration of alloxazine chromophores into the framework significantly extended the absorption spectrum into the visible range, allowing for photocatalytic oxidation of benzylic alcs. to aldehydes RC(O)H [R = 4-MeC6H4, 4-MeOC6H4, 4-t-BuC6H4, 2-thienyl] even with low-energy visible light. In addition, the activity of the heterogeneous COF photocatalyst was less dependent on the chosen solvent, making it more versatile compared to mol. alloxazines. Finally, the use of oxygen as the terminal oxidant renders FEAx-COF a promising and green heterogeneous photocatalyst.

Chemical Science published new progress about Alcohols Role: RCT (Reactant), RACT (Reactant or Reagent). 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Formula: C4H4N2O5.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia