191728-83-3

Usage

InChI:InChI=1/C10H8ClN3/c11-10-12-7-6-9(14-10)13-8-4-2-1-3-5-8/h1-7H,(H,12,13,14)

Upstream product

• 3934-20-1 2,6-Dichloropyrimidine 
• 62-53-3 aniline 

Downstream Products

• 260045-51-0 2-chloro-4-(N-(2-cyclohexylethyl)anilino)pyrimidine 
• 1236002-98-4 N₂-(4-methylpyridin-2-yl)-N₄-phenylpyrimidine-2,4-diamine 
• 1236003-02-3 N₂-(6-methoxypyridin-3-yl)-N₄-phenylpyrimidine-2,4-diamine 
• 1236003-05-6 N₂-(3-tert-butyl-1-methyl-1H-pyrazol-5-yl)-N₄-phenylpyrimidine-2,4-diamine 
• 1236003-08-9 N₂-(1-benzyl-1H-benzo[d]imidazol-2-yl)-N₄-phenylpyrimidine-2,4-diamine 
• 1454695-45-4 {2-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]pyrimidin-4-yl}phenylamine 
• 260045-52-1 2-chloro-4-(N-(3-morpholinopropyl)anilino)pyrimidine 
• 260045-55-4 4-Anilino-2-(4-(2,3-epoxypropoxy)anilino)pyrimidine 

Relevant academic research and scientific papers

Discovery of Diaminopyrimidine Carboxamide HPK1 Inhibitors as Preclinical Immunotherapy Tool Compounds

Hematopoietic progenitor kinase 1 (HPK1), a serine/threonine kinase, is a negative immune regulator of T cell receptor (TCR) and B cell signaling that is primarily expressed in hematopoietic cells. Accordingly, it has been reported that HPK1 loss-of-function in HPK1 kinase-dead syngeneic mouse models shows enhanced T cell signaling and cytokine production as well as tumor growth inhibition in vivo, supporting its value as an immunotherapeutic target. Herein, we present the structurally enabled discovery of novel, potent, and selective diaminopyrimidine carboxamide HPK1 inhibitors. The key discovery of a carboxamide moiety was essential for enhanced enzyme inhibitory potency and kinome selectivity as well as sustained elevation of cellular IL-2 production across a titration range in human peripheral blood mononuclear cells. The elucidation of structure-activity relationships using various pendant amino ring systems allowed for the identification of several small molecule type-I inhibitors with promising in vitro profiles.

Dual targeting of acetylcholinesterase and tau aggregation: Design, synthesis and evaluation of multifunctional deoxyvasicinone analogues for Alzheimer's disease

Development of multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for Alzheimer's disease (AD). Herein, we reported a new series of deoxyvasicinone analogues as dual inhibitor of acetylcholinesterase (AChE) and tau aggregation that function as multitargeted ligands for AD. All the multitargeted ligands 11(a-j) and 15(a-g) were designed, synthesized, and validated by 1HNMR, 13CNMR and mass spectrometry. All the synthesized compounds 11(a-j) and 15(a-g) were screened for their ability to inhibit AChE, BACE1, amyloid fibrillation, α-syn aggregation, and tau aggregation. All the screened compounds possessed weak inhibition of BACE-1, Aβ42 and α-syn aggregation. However, several compounds were identified as potential hits in the AChE inhibitory screening assay and cellular tau aggregation screening. Among all compounds, 11f remarkably inhibited AChE activity and cellular tau oligomerization at single-dose screening (10 μM). Moreover, 11f displayed a half-maximal inhibitory concentration (IC50) value of 0.91 ± 0.05 μM and half-maximal effective concentration (EC50) value of 3.83 ± 0.51 μM for the inhibition of AChE and cellular tau oligomerization, respectively. In addition, the neuroprotective effect of 11f was determined in tau-expressing SH-SY5Y cells incubated with Aβ oligomers. These findings highlighted the potential of 11f to function as a multifunctional ligand for the development of promising anti-AD drugs.

Discovery of novel 2,4-disubstituted pyrimidines as Aurora kinase inhibitors

In order to explore novel Aurora kinase inhibitors, a series of novel 2,4-disubstituted pyrimidines were designed, synthesized and evaluated their in vitro anti-proliferative activities against a panel of cancerous cell lines (A549, HCT-116 and MCF-7). Among them, compound 12a showed the moderate to high anti-proliferative activities against A549 (IC50 = 12.05 ± 0.45 μM), HCT-116 (IC50 = 1.31 ± 0.41 μM) and MCF-7 (IC50 = 20.53 ± 6.13 μM) cells, as well as the Aurora A and Aurora B inhibitory activities with the IC50 values of 309 nM and 293 nM, respectively. Furthermore, compound 12a induced apoptosis by upregulated the pro-apoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the molecular docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics prediction discovered that compound 12a exhibited good drug likeness using SwissADME. Taken together, these results indicated that 12a may be a potential anticancer compound that was worthy of further development as Aurora kinase inhibitor.

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.

METHODS OF REGIOSELECTIVE SYNTHESIS OF 2,4-DISUBSTITUTED PYRIMIDINES

The present invention relates to the novel regioselective syntheses of 2,4-disubstituted pyrimidines through sequential nucleophilic aromatic substitutions.

4-Aminoquinoline-Pyrimidine hybrids: Synthesis, antimalarial activity, heme binding and docking studies

A series of novel 4-aminoquinoline-pyrimidine hybrids has been synthesized and evaluated for their antimalarial activity. Several compounds showed promising in vitro antimalarial activity against both CQ-sensitive and CQ-resistant strains with high select

Synthesis of piperazine tethered 4-aminoquinoline-pyrimidine hybrids as potent antimalarial agents

A series of 4-aminoquinoline-pyrimidine hybrids linked through piperazine were synthesized and evaluated for their in vitro antimalarial activity against chloroquine (CQ)-sensitive and chloroquine (CQ)-resistant strains of Plasmodium falciparum and cytoto

KINASE INHIBITORS

Provided herein are kinase inhibiting compounds and methods of using the same.

Convenient preparation of 4-aryl-2-(heteroarylamino)pyrimidines and 4-anilino-2-(heteroarylamino)pyrimidines

4-Aryl-2-anilinopyrimidines and 2,4-dianilinopyrimidines are privileged structures found in many drug-like molecules and biologically active compounds. A method for the quick assembly of novel 4-aryl- and 4-anilino-2-(heteroarylamino)pyrimidines via Buchwald-Hartwig N-arylations at elevated temperatures under sealed tube conditions is reported. This method's convenience and practicality is demonstrated through the preparation of several novel non-nucleoside reverse transcriptase inhibitor (NNRTI) analogues.

Development of N-2,4-pyrimidine-N-phenyl-N′-phenyl ureas as inhibitors of tumor necrosis factor alpha (TNF-α) synthesis. Part 1

A new class of tumor necrosis factor alpha (TNF-α) synthesis inhibitors based on an N-2,4-pyrimidine-N-phenyl-N′-phenyl urea scaffold is described. Many of these compounds showed low-nanomolar activity against lipopolysaccharide stimulated TNF-α productio