Tag: M.W=200-250

Woodring, Jennifer L.; Bachovchin, Kelly A.; Brady, Kimberly G.; Gallerstein, Mitchell F.; Erath, Jessey; Tanghe, Scott; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. published the artcile< Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation>, Product Details of C4H2Br2N2, the main research area is anilinoquinazoline trypanosome inhibitor antimalarial malaria trypanosomiasis trypanosomicide; Human African trypanosomiasis; Leishmania major; Neglected tropical disease; Plasmodium falciparum; Target class repurposing; Trypanosoma brucei; Trypanosoma cruzi.

Human African trypanosomiasis (HAT) is a deadly disease in need of new chemotherapeutics that can cross into the central nervous system. The authors previously reported the discovery of (NEU-617), a small mol. with activity against T. brucei bloodstream proliferation. Further optimization of NEU-617 to improve the physicochem. properties (LogP, LLE, [1], and MPO score) [2] have led us to twelve sub-micromolar compounds, most importantly the headgroup variants I and II, and the linker variant III. Although these 3 compounds had reduced potency compared to NEU-617, they all had improved LogP, LLE and MPO scores. Cross-screening these analogs against other protozoan parasites uncovered IV with potent activity towards T. brucei, T. cruzi and L. major, while four others compounds showed activity towards P. falciparum D6. This reinforces the effectiveness of lead repurposing for the discovery of new protozoan disease therapeutics.

European Journal of Medicinal Chemistry published new progress about Antimalarials. 3921-01-5 belongs to class pyrimidines, and the molecular formula is C4H2Br2N2, Product Details of C4H2Br2N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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

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

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

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

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

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

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

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