280581-45-5

Upstream product

• 5750-76-5 2,4,5-trichloropyrimidine 
• 62-53-3 aniline 

Downstream Products

• 358789-02-3 4-anilino-2-(4-carboxyanilino)-5-chloropyrimidine 
• 280580-27-0 4-Anilino-5-chloro-2-{4-[2-hydroxy-3-(isopropylamino)propoxy]anilino}pyrimidine 
• 1341200-76-7 2-((2,5-dichloropyrimidin-4-yl)amino)benzene-1-sulfonyl chloride 
• 1022950-46-4 2,5-dichloro-N-(2-(pyrrolidin-1-ylsulfonyl)phenyl)pyrimidin-4-amine 
• 1341200-52-9 5-chloro-N₂-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-N₄-(2-(pyrrolidin-1-ylsulfonyl)phenyl)pyrimidine-2,4-diamine 
• 1620988-79-5 5-chloro-N²-(1-(methylsulfonyl)piperidin-4-yl)-N⁴-phenylpyrimidine-2,4-diamine 
• 1352244-87-1 5-chloro-N₂-[4-(4-methylpiperazin-1-yl)phenyl]-N₄-phenylpyrimidine-2,4-diamine trifluoroacetate (1:1) 

Relevant academic research and scientific papers

Discovery of a B-Cell Lymphoma 6 Protein-Protein Interaction Inhibitor by a Biophysics-Driven Fragment-Based Approach

B-cell lymphoma 6 (BCL6) is a transcriptional factor that expresses in lymphocytes and regulates the differentiation and proliferation of lymphocytes. Therefore, BCL6 is a therapeutic target for autoimmune diseases and cancer treatment. This report presen

Discovery and in Vivo Anti-inflammatory Activity Evaluation of a Novel Non-peptidyl Non-covalent Cathepsin C Inhibitor

Cathepsin C (Cat C) participates in inflammation and immune regulation by affecting the activation of neutrophil serine proteases (NSPs). Therefore, cathepsin C is an attractive target for treatment of NSP-related inflammatory diseases. Here, the complete discovery process of the first potent "non-peptidyl non-covalent cathepsin C inhibitor"was described with hit finding, structure optimization, and lead discovery. Starting with hit 14, structure-based optimization and structure-activity relationship study were comprehensively carried out, and lead compound 54 was discovered as a potent drug-like cathepsin C inhibitor both in vivo and in vitro. Also, compound 54 (with cathepsin C Enz IC50 = 57.4 nM) exhibited effective anti-inflammatory activity in an animal model of chronic obstructive pulmonary disease. These results confirmed that the non-peptidyl and non-covalent derivative could be used as an effective cathepsin C inhibitor and encouraged us to continue further drug discovery on the basis of this finding.

Discovery of 2,4-pyrimidinediamine derivatives as potent dual inhibitors of ALK and HDAC

Combination of anaplastic lymphoma kinase (ALK) inhibitor with histone deacetylases (HDAC) inhibitor could exert synergistically anti-proliferative effects on ALK positive non-small cell lung cancer (NSCLC) na?ve or resistant cells. In this work, we designed and synthesized a series of 2,4-pyrimidinediamine derivatives as dual ALK and HDAC inhibitors based on pharmacophore merged strategy. Among which, compound 10f displayed the most potent and balanced inhibitory activity against ALK (IC50 = 2.1 nM) and HDAC1 (IC50 = 7.9 nM), respectively. In particular, 10f was also potent against the frequently observed Crizotinib-resistant ALKL1196M (IC50 = 1.7 nM) as well as the Ceritinib-resistant ALKG1202R (IC50 = 0.4 nM) mutants. In antiproliferative activity assay, 10f exhibited impressive activity on ALK-addicted cancer cell lines at low micromole concentrations, which was comparable to that of Crizotinib and Ceritinib. Further flow cytometric analysis indicated that 10f could effectively induce cell death via cell apoptosis and cell cycle arrest. Taken together, these results suggested 10f would be a promising lead compound for the ALK-positive NSCLC treatment, especially the Ceritinib- or Crizotinib-resistant NSCLC.

Discovery and SARs of 5-Chloro- N4-phenyl- N2-(pyridin-2-yl)pyrimidine-2,4-diamine Derivatives as Oral Available and Dual CDK 6 and 9 Inhibitors with Potent Antitumor Activity

Cyclin-dependent kinases (CDKs) are promising therapeutic targets for cancer therapy. Herein, we describe our efforts toward the discovery of a series of 5-chloro-N4-phenyl-N2-(pyridin-2-yl)pyrimidine-2,4-diamine derivatives as dual CDK6 and 9 inhibitors. Intensive structural modifications lead to the identification of compound 66 as the most active dual CDK6/9 inhibitor with balancing potency against these two targets and good selectivity over CDK2. Further biological studies revealed that compound 66 was directly bound to CDK6/9, resulting in suppression of their downstream signaling pathway and inhibition of cell proliferation by blocking cell cycle progression and inducing cellular apoptosis. More importantly, compound 66 significantly inhibited tumor growth in a xenograft mouse model with no obvious toxicity, indicating the promising therapeutic potential of CDK6/9 dual inhibitors for cancer treatment. Therefore, the above results are of great importance in the development of dual CDK6/9 inhibitors for cancer therapy.

5-chloro-pyrimidine-2, 4-diamine compound as well as preparation method and application thereof

The invention discloses a 5-chloro-pyrimidine-2, 4-diamine compound as well as a preparation method and an application thereof. The 5-chloro-pyrimidine-2, 4-diamine compound is shown as a formula (I)or a formula (II), wherein R1 is selected from any one g

Discovery of Novel Janus Kinase (JAK) and Histone Deacetylase (HDAC) Dual Inhibitors for the Treatment of Hematological Malignancies

Concurrent inhibition of Janus kinase (JAK) and histone deacetylase (HDAC) could potentially improve the efficacy of the HDAC inhibitors in the treatment of cancers and resolve the problem of HDAC inhibitor resistance in some tumors. Here, a novel series

Compound used as ALK (anaplastic lymphoma kinase) inhibitor and application thereof

The invention discloses a compound shown in a formula I, and pharmaceutically acceptable salts, stereoisomers, solvates or predrugs. The symptoms are defined in claim requirements. The compound shownin the formula I has good inhibiting activity on ALK (anaplastic lymphoma kinase), and can be used for preparing medicines for adjusting the activity of the ALK activity or treating the ALK-related diseases, especially nonsmall-cell lung cancer drugs. (The formula I is shown in the attached figure.).

Design, Synthesis, and Antitumor Evaluation of 4-Amino-(1H)-pyrazole Derivatives as JAKs Inhibitors

Abnormalities in the JAK/STAT signaling pathway lead to many diseases such as immunodeficiency, inflammation, and cancer. Herein, we designed and synthesized a series of 4-amino-(1H)-pyrazole derivatives as potent JAKs inhibitors for cancer treatment. Res

Nucleophilic Aromatic Substitution Reactions in Water Enabled by Micellar Catalysis

Given the huge dependence on dipolar, aprotic solvents such as DMF, DMSO, DMAc, and NMP in nucleophilic aromatic substitution reactions (SNAr), a simple and environmentally friendly alternative is reported. Use of a "benign-by-design" nonionic surfactant, TPGS-750-M, in water enables nitrogen, oxygen, and sulfur nucleophiles to participate in SNAr reactions. Aromatic and heteroaromatic substrates readily participate in this micellar catalysis, which takes place at or near ambient temperatures.

PHOSPHOROUS DERIVATIVES AS KINASE INHIBITORS

The invention features compounds of the general formula: in which the variable groups are as defined herein, and to their preparation and use.