Tag: M.W=150-200

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

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

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

Makita, Yoshimasa; Kawaguchi, Shin-ichi; Fujiwara, Shin-ichi published the artcile< Characterization and antitumor activity of furazano[3,4-g]pteridine-2,4(1H,3H)-dione>, Product Details of C4H4N2O5, the main research area is furazanopteridinedione preparation antitumor crystal structure emission absorption spectra.

Structural characterization and properties of furazano[3,4-g]pteridine-2,4(1H,3H)-dione by X-ray crystal structure anal. was reported and evaluated for its antitumor activity. The IC50 value of furazano[3,4-g]pteridine-2,4(1H,3H)-dione was 172μM, as determined using HeLa cells.

Heterocycles published new progress about Absorption spectra. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Product Details of C4H4N2O5.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Vorbrueggen, Helmut; Ruh-Pohlenz, Carmen published the artcile< Synthesis of nucleosides>, Name: 4-Methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine, the main research area is review Synthesis; review Nucleosides.

A review of the article Synthesis of nucleosides.

Organic Reactions (Hoboken, NJ, United States) published new progress about Organic synthesis. 84955-32-8 belongs to class pyrimidines, and the molecular formula is C7H8N4O, Name: 4-Methoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Xu, Hongtao; Gu, Yuang; Zhang, Shuning; Xiong, Huan; Ma, Fei; Lu, Fengping; Ji, Qun; Liu, Lili; Ma, Peixiang; Hou, Wei; Yang, Guang; Lerner, Richard A. published the artcile< A Chemistry for Incorporation of Selenium into DNA-Encoded Libraries>, COA of Formula: C7H7ClN2O2, the main research area is selenium DNA encoded library preparation; C−H activation; DNA-encoded library; benzoselenazolone; rhodium; selenylation.

Conventional direct C-H selenylation suffers from simple selenation with limited atom economy and complicated reaction system. The authors designed benzoselenazolone as a novel bifunctional selenide reagent for both off- and on-DNA C-H selenylation under rhodium(III) catalysis. Using benzoselenazolone gave a series of selenylation products containing an adjacent aminoacyl group in a fast and efficient way, with high atom economy. The synthetic application of this method was demonstrated by taking advantage of the amide functionality as a nucleophile, directing group, and amide coupling partner. This work shows great potential in facilitating rapid construction of selenium-containing DNA-encoded chem. libraries (SeDELs), and lays the foundation for the development of selenium-containing drugs.

Angewandte Chemie, International Edition published new progress about Azoles Role: RCT (Reactant), RACT (Reactant or Reagent) (benzoselenazolones). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, COA of Formula: C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Matyugina, Elena; Novikov, Mikhail; Babkov, Denis; Ozerov, Alexander; Chernousova, Larisa; Andreevskaya, Sofia; Smirnova, Tatiana; Karpenko, Inna; Chizhov, Alexander; Muthu, Pravin; Lutz, Stefan; Kochetkov, Sergei; Seley-Radtke, Katherine L.; Khandazhinskaya, Anastasia L. published the artcile< 5-Arylaminouracil Derivatives: New Inhibitors of Mycobacterium tuberculosis>, HPLC of Formula: 4956-05-2, the main research area is arylaminouracil preparation Mycobacterium tuberculosis tuberculostatic; Mycobacterium tuberculosis; carbocyclic nucleosides; uracil derivatives.

Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-5-(phenylamino)uracils, and 1,3-di-(4′-hydroxy-2′-cyclopenten-1′-yl)-5-(phenylamino)uracils, were synthesized and screened for potential antimicrobial activity. Most of compounds had a neg. effect on the growth of the Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-3-(4”’-hydroxy-2”’-cyclopenten-1”’-yl)-5-(4”-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC90 5 μg/mL). In addition, the thymidylate kinase of M. tuberculosis was evaluated as a possible enzymic target.

Chemical Biology & Drug Design published new progress about Mycobacterium tuberculosis. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, HPLC of Formula: 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bellenie, Benjamin R.; Cheung, Kwai-Ming J.; Varela, Ana; Pierrat, Olivier A.; Collie, Gavin W.; Box, Gary M.; Bright, Michael D.; Gowan, Sharon; Hayes, Angela; Rodrigues, Matthew J.; Shetty, Kartika N.; Carter, Michael; Davis, Owen A.; Henley, Alan T.; Innocenti, Paolo; Johnson, Louise D.; Liu, Manjuan; de Klerk, Selby; Le Bihan, Yann-Vai; Lloyd, Matthew G.; McAndrew, P. Craig; Shehu, Erald; Talbot, Rachel; Woodward, Hannah L.; Burke, Rosemary; Kirkin, Vladimir; van Montfort, Rob L. M.; Raynaud, Florence I.; Rossanese, Olivia W.; Hoelder, Swen published the artcile< Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders>, Formula: C5H4Cl2N2S, the main research area is preparation benzimidazolone inhibitor BCL6 interaction repressor lymphoma.

Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). Herein we report the discovery of a series of benzimidazolone inhibitors of the protein-protein interaction between BCL6 and its co-repressors. A subset of these inhibitors were found to cause rapid degradation of BCL6, and optimization of pharmacokinetic properties led to the discovery of 5-((5-chloro-2-((3R,5S)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)pyrimidin-4-yl)amino)-3-(3-hydroxy-3-methylbutyl)-1-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (CCT369260), which reduces BCL6 levels in a lymphoma xenograft mouse model following oral dosing.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 99469-85-9 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2S, Formula: C5H4Cl2N2S.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kickinger, Stefanie; Al-Khawaja, Anas; Haugaard, Anne Staehr; Lie, Maria E. K.; Bavo, Francesco; Loeffler, Rebekka; Damgaard, Maria; Ecker, Gerhard F.; Froelund, Bente; Wellendorph, Petrine published the artcile< Exploring the molecular determinants for subtype-selectivity of 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid analogs as betaine/GABA transporter 1 (BGT1) substrate-inhibitors>, Application of C7H7ClN2O2, the main research area is amino tetrahydropyrimidine carboxylic acid betaine GABA transporter substrate inhibitor.

We have previously identified 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid (ATPCA) as the most potent substrate-inhibitor of the betaine/GABA transporter 1 (BGT1) (IC50 2.5 μM) reported to date. Herein, we characterize the binding mode of 20 novel analogs and propose the mol. determinants driving BGT1-selectivity. A series of N1-, exocyclic-N-, and C4-substituted analogs was synthesized and pharmacol. characterized in radioligand-based uptake assays at the four human GABA transporters (hGATs) recombinantly expressed in mammalian cells. Overall, the analogs retained subtype-selectivity for hBGT1, though with lower inhibitory activities (mid to high micromolar IC50 values) compared to ATPCA. Further characterization of five of these BGT1-active analogs in a fluorescence-based FMP assay revealed that the compounds are substrates for hBGT1, suggesting they interact with the orthosteric site of the transporter. In silico-guided mutagenesis experiments showed that the non-conserved residues Q299 and E52 in hBGT1 as well as the conformational flexibility of the compounds potentially contribute to the subtype-selectivity of ATPCA and its analogs. Overall, this study provides new insights into the mol. interactions governing the subtype-selectivity of BGT1 substrate-inhibitors. The findings may guide the rational design of BGT1-selective pharmacol. tool compounds for future drug discovery.

Scientific Reports published new progress about Aminopyrimidines Role: PAC (Pharmacological Activity), PRP (Properties), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Application of C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Nakazawa, Junichi; Watatani, Mitsuo published the artcile< Pyrimidine derivatives. II. Transetherification in pyrimidine derivatives>, COA of Formula: C5H6ClN3O, the main research area is .

Transetherification reactions of 2-methoxy-, 2-ethoxy-4-amino-6-chloropyrimidine, and 2,6-dimethoxy- and 2,6-diethoxy-4-aminopyrimidine at the alkoxy groups at 2- and 6-position by the treatment with NaOMe or NaOEt were investigated and found that the 2-position was more reactive than 4-position and the MeO group more readily underwent transetherification reaction than the EtO group. In 5-substituted pyrimidines with an electroneg. group, the MeOH at 2-, 4-, or 6-position was readily eliminated owing to its further higher reactivity. Manufacture of the following new compounds was also described: a mixture of 38.4 g. barbituric acid 24.3 g. KCN and 144 g. urea was melted at 143-8° 4 hrs., then cooled to 100°, 240 cc. H2O added, stirred 30 min., cooled to below 50°, acidified with HCl, and filtered to give 56.5 g. 2,4,6-trihydroxy-5-pyrimidinecarboxamide (I), fiberlike crystals, m. above 360°. I (8.6 g.) was refluxed with 61 g. POCl3 and 6 g. PhNMe2 1.5 hrs., decomposed with ice, extracted with C6H6, the extract evaporated, and the residue purified by sublimation to give 2,4,6-trichloro-5-cyanopyrimidine (II), plates, m. 122-3.5°. II (1 g.) was added to a solution of 0.67 g. Na in 30 cc. MeOH, refluxed 4 hrs., filtered, the filtrate concentrated, H2O added, and the whole neutralized with HCl to give 2,4-dimethoxy-5-cyano-6-hydroxypyrimidine (III), needles, m. 217-18° (decomposition) (MeOH). III (0.3 g.) was heated 2 hrs. with 30 cc. 5% KOH solution on a steam bath, acidified with HCl, and the mixture filtered to give 2,4,6-trihydroxy-5-cyanopyrimidine, m. above 360°.

Takamine Kenkyusho Nenpo published new progress about Alcoholysis. 3286-55-3 belongs to class pyrimidines, and the molecular formula is C5H6ClN3O, COA of Formula: C5H6ClN3O.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia