Pyrimidines

Hin, Niyada; Duvall, Bridget; Ferraris, Dana; Alt, Jesse; Thomas, Ajit G.; Rais, Rana; Rojas, Camilo; Wu, Ying; Wozniak, Krystyna M.; Slusher, Barbara S.; Tsukamoto, Takashi published the artcile< 6-Hydroxy-1,2,4-triazine-3,5(2H,4H)-dione Derivatives as Novel D-Amino Acid Oxidase Inhibitors>, Quality Control of 4956-05-2, the main research area is hydroxytriazinedione preparation amino acid oxidase inhibitor.

A series of 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives were synthesized as inhibitors of D-amino acid oxidase (DAAO). Many compounds in this series were found to be potent DAAO inhibitors, with IC50 values in the double-digit nanomolar range. The 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione pharmacophore appears metabolically resistant to O-glucuronidation unlike other structurally related DAAO inhibitors. Among them, compound I was found to be selective over a number of targets and orally available in mice. Furthermore, oral coadministration of D-serine with I enhanced the plasma levels of D-serine in mice compared to the oral administration of D-serine alone, demonstrating its ability to serve as a pharmacoenhancer of D-serine.

Journal of Medicinal Chemistry published new progress about Alkylation. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Quality Control of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

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

Mohammadi, Ali; Eshghi, Hossein; Bakavoli, Mehdi; Hadizadeh, Farzin; Moradi, Hassanali published the artcile< Synthesis of novel 3-substituted-5H-benzo[5,6][1, 4]thiazino[3,2-e][1,2,4]triazines and their 15-lipoxygenase inhibitory activity>, Synthetic Route of 4956-05-2, the main research area is benzothiazinotriazine preparation mol docking lipoxygenase inhibitor.

A new group of 3-substituted-5H-benzo[5,6][1,4]thiazino[3,2-e][1,2,4]triazines I (R = morpholin-4-yl, pyrrolidin-1-yl, 4-methylpiperidin-1-yl, etc.) was designed, synthesized and evaluated as inhibitors of 15-lipoxygenase (15-LO), and the results were compared with those of standard ligand 4-methyl-2-(4-methylpiperazin-1-yl)pyrimido[4,5-b][1,4]benzothiazine (4-MMPB). Among the newly designed ligands I, compound I (R = 4-phenylpiperazin-1-yl) showed the best IC50 of 15-LO inhibition (IC50 = 38 μM). The docking calculations were performed in MOE software based on the function of force-field scoring, in order to study the interaction of these new compounds I and standard ligand with 15-LO. The docking study implied that these ligands I have hydrogen bond interaction with the residue of active site of 15-LO.

Journal of the Iranian Chemical Society published new progress about Cyclic amines Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Synthetic Route of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yoon, Hyung; Galls, Alexandra; Rozema, Soren D.; Miller, Scott J. published the artcile< Atroposelective Desymmetrization of Resorcinol-Bearing Quinazolinones via Cu-Catalyzed C-O Bond Formation>, Formula: C7H7ClN2O2, the main research area is resorcinol quinazolinone preparation enantioselective; quinazolinone aryl bromide Ullmann coupling atroposelective desymmetrization copper catalyst.

Enantioselective Cu-catalyzed C-O cross coupling reactions yielding atropisomeric resorcinol-bearing quinazolinones have been developed. By utilizing a new guanidinylated dimeric peptidic ligand, products I (R = H, Br, R1 = H, NO2, CF3, R2 = Me, Et, R3 = H, Me, OMe, R4 = H, OMe, X = CH; R = R1 = R3 = R4 = H, R2 = Me, X = N) were generated in good yields with excellent stereocontrol. The transformation was readily scalable and a range of product derivatizations were performed.

Organic Letters published new progress about Aryl bromides Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Formula: C7H7ClN2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Chen, Yong; Wang, Xiaoyan; Xiang, Wei; He, Lin; Tang, Minghai; Wang, Fang; Wang, Taijin; Yang, Zhuang; Yi, Yuyao; Wang, Hairong; Niu, Ting; Zheng, Li; Lei, Lei; Li, Xiaobin; Song, Hang; Chen, Lijuan published the artcile< Development of Purine-Based Hydroxamic Acid Derivatives: Potent Histone Deacetylase Inhibitors with Marked in Vitro and in Vivo Antitumor Activities>, HPLC of Formula: 89793-12-4, the main research area is purine hydroxamic acid derivative preparation histone deacetylase inhibitor cancer.

In the present study, a series of novel histone deacetylase (HDAC) inhibitors using the morpholinopurine as the capping group were designed and synthesized. Several compounds demonstrated significant HDAC inhibitory activities and antiproliferative effects against diverse human tumor cell lines. Among them, compound 10o was identified as a potent class I and class IIb HDAC inhibitor with good pharmaceutical profile and druglike properties. Western blot anal. further confirmed that 10o more effectively increased acetylated histone H3 than panobinostat (LBH-589) and vorinostat (SAHA) at the same concentration in vitro. In in vivo efficacy evaluations of HCT116, MV4-11, Ramos, and MM1S xenograft models, 10o showed higher efficacy than SAHA or LBH-589 without causing significant loss of body weight and toxicity. All the results indicated that 10o could be a suitable candidate for treatment of both solid and hematol. cancer.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, HPLC of Formula: 89793-12-4.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Lee, Kuan Han; Han, Chein Hwa; Hwang, Long Chih; Wang, Eng Chi; Tzeng, Cherng Chyi published the artcile< Acyclic nucleosides. Part 3: Synthesis of certain 1-[(1,3-dihydroxy-2-propoxy)methyl]-6-azauracils as potential antiviral agents>, Category: pyrimidines, the main research area is acyclic nucleoside azauracil preparation virucide; hydroxypropoxymethylazauracil acyclic nucleoside.

A number of 6-azauracils were trimethylsilylated and then coupled with 1,3-dibenzyloxy-2-chloromethoxypropane to give 1-[(1,3-dibenzyloxy-2-propoxy)methyl]-6-azauracils which were debenzylated with either BCl3 or Pd2O to yield the title compounds I (R = H, Me, Cl, Br).

Gaoxiong Yixue Kexue Zazhi published new progress about Acyclonucleosides Role: SPN (Synthetic Preparation), PREP (Preparation). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia