945895-80-7

Upstream product

• 3934-20-1 2,6-Dichloropyrimidine 
• 140-75-0 para-fluorobenzylamine 

Downstream Products

• 1391531-29-5 N⁽²⁾-(1-benzylpiperidin-4-yl)-N⁽⁴⁾-(4-fluorobenzyl)pyrimidine-2,4-diamine 

Relevant academic research and scientific papers

Compound as well as preparation method and application thereof as c-Met inhibitor

The invention provides a compound as well as a preparation method and application thereof as a c-Met inhibitor. The compound has a structure as shown in a formula (X) or an isomer of the compound in the formula (X) or a pharmaceutically acceptable slat of the compound, wherein A is hydrogen or B is shown as the specification or C does not exist or is a benzene ring, and C forms a quinazoline grouptogether with a parent nucleus structure when being the benzene ring; L1 is -NH-CH2- or -O-; L2 does not exist or is -NH-; X is C or N; Y is O or S; R1 is halogen or -NO2; R2 is shown as the specification or is -COR5; R3 is selected from halogen, alkyl and alkoxy; each of R4 and R5 is an independent C3-C6 saturated or unsaturated cycloalkyl, aryl or heteroaryl; and the cycloalkyl, aryl or heteroaryl is substituted or unsubstituted, the substituent group is selected from halogen, nitryl, alkyl and substituent alkyl.

De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus

Dengue fever is a mosquito-borne viral disease that has become a major public health concern worldwide. This disease presents with a wide range of clinical manifestations, from a mild cold-like illness to the more serious hemorrhagic dengue fever and dengue shock syndrome. Currently, neither an approved drug nor an effective vaccine for the treatment are available to fight the disease. The envelope protein (E) is a major component of the virion surface. This protein plays a key role during the viral entry process, constituting an attractive target for the development of antiviral drugs. The crystal structure of the E protein reveals the existence of a hydrophobic pocket occupied by the detergent n-octyl-β-d-glucoside (β-OG). This pocket lies at the hinge region between domains I and II and is important for the low pH-triggered conformational rearrangement required for the fusion of the virion with the host's cell. Aiming at the design of novel molecules which bind to E and act as virus entry inhibitors, we undertook a de novo design approach by “growing” molecules inside the hydrophobic site (β-OG). From more than 240000 small-molecules generated, the 2,4 pyrimidine scaffold was selected as the best candidate, from which one synthesized compound displayed micromolar activity. Molecular dynamics-based optimization was performed on this hit, and thirty derivatives were designed in silico, synthesized and evaluated on their capacity to inhibit dengue virus entry into the host cell. Four compounds were found to be potent antiviral compounds in the low-micromolar range. The assessment of drug-like physicochemical and in vitro pharmacokinetic properties revealed that compounds 3e and 3h presented acceptable solubility values and were stable in mouse plasma, simulated gastric fluid, simulated intestinal fluid, and phosphate buffered saline solution.

Design, synthesis and biological evaluation of pyrimidine-based derivatives as VEGFR-2 tyrosine kinase inhibitors

Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has already become an attractive approach for cancer therapy. In this study, a novel pyrimidine-based derivative 7j was designed as lead compound, and three series of potent VEGFR-2 inhibitors were synthesized and biologically evaluated against A549 and HepG2 cell lines. Compounds 7d, 9s and 13n exhibited superior inhibitory activities against A549 cell with IC50 ranged from 9.19 to 13.17 μM and HepG2 cell with IC50 ranged from 11.94 to 18.21 μM compared to those of Pazopanib (IC50 = 21.18 and 36.66 μM). In addition, molecular docking study was performed to investigate the binding capacity and binding mode between target compounds and VEGFR-2.

SUBSTITUTED AZAHETEROCYCLES FOR THE TREATMENT OF CANCER

The invention provides novel substituted azaheterocyclic compounds according to Formula (I), their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

Development and evaluation of multifunctional agents for potential treatment of Alzheimer's disease: Application to a pyrimidine-2,4-diamine template

We investigated a group of 2-benzylpiperidin-N-benzylpyrimidin-4-amines with various electron-withdrawing or electron-donating groups (EWGs or EDGs, respectively) as multi-targeted Alzheimer's disease (AD) therapeutics. The synthesized derivatives were sc