Category: 18740-39-1

Zhi, Yanle; Li, Baoquan; Yao, Chao; Li, Hongmei; Chen, Puzhou; Bao, Jiyin; Qin, Tianren; Wang, Yue; Lu, Tao; Lu, Shuai published the artcile< Discovery of the selective and efficacious inhibitors of FLT3 mutations>, Quality Control of 18740-39-1, the main research area is pyrazole carboxamide preparation FLT3 inhibitor mutation antitumor leukemia; AML; Acute myeloid; FLT3; FMS-Like tyrosine kinase 3 inhibitors; Leukemia.

Fms-like tyrosine kinase 3 (FLT3) is among the most frequently mutated protein in acute myeloid leukemia (AML), which has been confirmed as an important drug target for AML chemotherapy. Starting from the lead compound LT-106-175, a series of 1-H-pyrazole-3-carboxamide derivatives were synthesized to improve the FLT3 inhibitory potency and selectivity. Among them, compound 50 (4-((2-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino)-N-(4-(piperazin-1-yl)phenyl)-1H-pyrazole-3-carboxamide) was identified as a highly potent and selective FLT3 inhibitor (IC50 = 0.213 nM), which showed equal activities against various mutants of FLT3 including FLT3 (ITD)-D835V and FLT3 (ITD)-F691L that is resistant to quizartinib. Compound 50 also exhibited efficacy against the human AML cell line MV4-11 (IC50 = 16.1 nM) harboring FLT3-ITD mutants. Inversely, compound 50 displayed no cytotoxicity to FLT3-independent cells, and the biochem. analyses showed that its effects were related to the inhibition of FLT3 signal pathways. Addnl., compound 50 induced apoptosis in MV4-11 cell as demonstrated by flow cytometry. Moreover, compound 50 showed enhanced metabolic stability. Altogether, it was concluded that compound 50 could be a promising FLT3 inhibitor for further developing therapeutic remedy of AML.

European Journal of Medicinal Chemistry published new progress about Acute myeloid leukemia. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Quality Control of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ife, Robert J.; Brown, Thomas H.; Blurton, Peter; Keeling, David J.; Leach, Colin A.; Meeson, Malcolm L.; Parsons, Michael E.; Theobald, Colin J. published the artcile< Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 5. Substituted 2,4-Diaminoquinazolines and Thienopyrimidines>, Related Products of 18740-39-1, the main research area is quinazolinamine thienopyrimidinamine quinazolinediamine.

Quinazolines bearing a secondary [4-(arylamino)] substituent demonstrate a structure-activity relationship for inhibition of the gastric (H+/K+)-ATPase different from the previously described 3-acylquinolines, suggesting that, although these compounds are also K+-competitive, they probably bind to the enzyme in a different orientation. Compounds bearing a tertiary 4-(arylamino) substituent, however, in particular 4-(N-methylarylamino), appear to possess an structure-activity relationship quite similar to the 3-acylquinolines. Compounds possessing both a 4-(N-methylarylamino) substituent and a 2-(arylamino) substituent proved to be very potent, K+-competitive inhibitors of K+-stimulated ATPase activity with Ki values down to 12 nM. Some compounds also proved to be effective inhibitors of stimulated acid secretion in both the rat and dog when dosed i.v. However, although a number of these demonstrated activity after oral administration in dogs, the level and variability precluded further evaluation.

Journal of Medicinal Chemistry published new progress about Structure-activity relationship, ATPase-inhibiting. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Related Products of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Dexheimer, Thomas S.; Rosenthal, Andrew S.; Luci, Diane K.; Liang, Qin; Villamil, Mark A.; Chen, Junjun; Sun, Hongmao; Kerns, Edward H.; Simeonov, Anton; Jadhav, Ajit; Zhuang, Zhihao; Maloney, David J. published the artcile< Synthesis and Structure-Activity Relationship Studies of N-Benzyl-2-phenylpyrimidin-4-amine Derivatives as Potent USP1/UAF1 Deubiquitinase Inhibitors with Anticancer Activity against Nonsmall Cell Lung Cancer>, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is benzylphenylpyrimidinamine antitumor neoplasm deubiquitinase.

Deregulation of ubiquitin conjugation or deconjugation has been implicated in the pathogenesis of many human diseases including cancer. The deubiquitinating enzyme USP1 (ubiquitin-specific protease 1), in association with UAF1 (USP1-associated factor 1), is a known regulator of DNA damage response and has been shown as a promising anticancer target. To further evaluate USP1/UAF1 as a therapeutic target, the authors conducted a quant. high throughput screen of >400000 compounds and subsequent medicinal chem. optimization of small mols. that inhibit the deubiquitinating activity of USP1/UAF1. Ultimately, these efforts led to the identification of ML323 (70) and related N-benzyl-2-phenylpyrimidin-4-amine derivatives, which possess nanomolar USP1/UAF1 inhibitory potency. Moreover, the authors demonstrate a strong correlation between compound IC50 values for USP1/UAF1 inhibition and activity in nonsmall cell lung cancer cells, specifically increased monoubiquitinated PCNA (Ub-PCNA) levels and decreased cell survival. The results establish the druggability of the USP1/UAF1 deubiquitinase complex and its potential as a mol. target for anticancer therapies.

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

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

Liu, Kevin G.; Kim, Ji-In; Olszewski, Kellen; Barsotti, Anthony M.; Morris, Koi; Lamarque, Christophe; Yu, Xuemei; Gaffney, Jack; Feng, Xiao-Jiang; Patel, Jeegar P.; Poyurovsky, Masha V. published the artcile< Discovery and Optimization of Glucose Uptake Inhibitors>, Electric Literature of 18740-39-1, the main research area is glucose transporters inhibitors GLUT1 GLUT3 bioavailable ADME SAR.

Aerobic glycolysis, originally identified by Warburg as a hallmark of cancer, has recently been implicated in immune cell activation and growth. Glucose, the starting material for glycolysis, is transported through the cellular membrane by a family of glucose transporters (GLUTs). Therefore, targeting glucose transporters to regulate aerobic glycolysis is an attractive approach to identify potential therapeutic agents for cancers and autoimmune diseases. Herein, we describe the discovery and optimization of a class of potent, orally bioavailable inhibitors of glucose transporters, targeting both GLUT1 and GLUT3.

Journal of Medicinal Chemistry published new progress about Autoimmune disease. 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

Prabhakar, Virupakshi; Babu, Sangu Jagadish; Jyothi, Sangu V. N. Lalitha Siva; Lahari, Sangu V. N.; Bandi, Venkateswarlu published the artcile< Synthesis, structural elucidation and anti-bacterial evaluation of some novel heterocyclic molecules derived from thieno[2,3-d]pyrimidine as a core unit>, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is thienopyrimidinepyrazole preparation antibacterial antifungal.

A series of novel 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2-substituted phenyl/heterocyclic thieno[2,3-d]pyrimidine derivatives I (R = Ph, 4-MeC6H4, 4-MeOC6H4, etc.) were synthesized by a facile five-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The final compounds were screened for their anti-bacterial activity against Bacillus subtilis and Staphylococcus aureus from Gram pos. group of bacteria and Escherichia coli and Klebsiella pneumonia from Gram neg. group of bacteria and antifungal activity against Candida albicans and Aspergillus flavus. Anti-bacterial and anti-fungal activities were evaluated and compared with the standard drugs such as amoxicillin and ketoconazole. From anti-bacterial and antifungal activity screening results, it has been observed that compounds I (R = thiophen-2-yl, indol-5-yl, 4-F3CC6H4, pyridin-3-yl) possess good activity.

Organic Chemistry: Current Research published new progress about Antibacterial agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Safety of 2,4-Dichlorothieno[2,3-d]pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Deng, Jifeng; Peng, Li; Zhang, Guicheng; Lan, Xiaobing; Li, Chufang; Chen, Fuxin; Zhou, Yayao; Lin, Zuoxian; Chen, Ling; Dai, Renke; Xu, Hongjiang; Yang, Ling; Zhang, Xiquan; Hu, Wenhui published the artcile< The highly potent and selective dipeptidyl peptidase IV inhibitors bearing a thienopyrimidine scaffold effectively treat type 2 diabetes>, Category: pyrimidines, the main research area is thienopyrimidine preparation DDP IV inhibitor treatment diabetes; aminothiophenecarboxylate cyclization chlorination oxygenation alkylation substitution.

Some dipeptidyl peptidase IV inhibitors, e.g., I, were designed based on alogliptin using a scaffold-hopping strategy. All of the compounds constructed on a thienopyrimidine scaffold demonstrated good inhibition and selectivity for DPP-IV. Compound I exhibited subnanomolar (IC50 = 0.33 nM) DPP-IV inhibitory activity, good in vivo efficacy and an acceptable pharmacokinetic profile. A pharmacokinetic-driven optimization of I may lead to a class of clin. candidate DPP-IV inhibitors.

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

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