761440-08-8

Upstream product

• 610-14-0 2-nitrobenzyl chloride 
• 3400-29-1 N-methyl-2-nitrobenzamide 
• 552-16-9 ortho-nitrobenzoic acid 
• 118-48-9 isatoic anhydride 
• 5750-76-5 2,4,5-trichloropyrimidine 
• 74-89-5 methylamine 
• 4141-08-6 2-Amino-N-methylbenzamid 

Downstream Products

• 761437-28-9 TAE226 
• 1022971-46-5 2-[5-chloro-2-(5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide 
• 1022955-88-9 2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide 
• 1439934-41-4 2-((5-chloro-2-((4-(piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide 
• 1391712-60-9 2-[[5-chloro-2-[[(6S)-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1-methoxy-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-yl]-amino]pyrimidin-4-yl]amino]-N-methylbenzamide 

Relevant academic research and scientific papers

Structure-Based Design, Synthesis, and Characterization of the First Irreversible Inhibitor of Focal Adhesion Kinase

Focal Adhesion Kinase signaling pathway and its functions have been involved in the development and aggressiveness of tumor malignancy, it then presents a promising cancer therapeutic target. Several reversible FAK inhibitors have been developed and are b

Discovery and antitumor activity of Benzo[d]imidazol-containing 2,4-diarylaminopyrimidine analogues as ALK inhibitors with mutation-combating effects

To address drug resistance caused by ALK kinase mutations, a series of novel 2,4-diarylaminopyrimidine (DAAP) analogues were designed by incorporating 1H-benzo[d]imidazol motif onto the maternal framework. All compounds were efficiently synthesized and an

Design, synthesis, and biological evaluation of novel covalent inhibitors targeting focal adhesion kinase

Forty-one new focal adhesion kinase (FAK) covalent inhibitors were designed and synthesized based on FAK inhibitor TAE226. Compound 11w displayed the highest inhibition of FAK with an IC50 value of 35 nM and exhibited potent anticancer activity against Hela, HCT116 and MDA-MB-231 cell lines with IC50 values of 0.41, 0.01 and 0.11 μM respectively, compared to TAE226 (2.68, 0.64 and 4.19 μM respectively). 11w also inhibited the clone formation and migration of HCT-116 cells and stimulated cell cycle arrest in the G2/M phase, inducing tumor cell apoptosis. Compound 11w formed a covalent bond with the Cys427 residue of FAK in a docking model, inhibiting the autophosphorylation of FAK and downstream proteins in a dose-dependent manner. Moreover, 11w showed adequate oral bioavailability of 21.02%. A 74.20% inhibition of tumor growth in the HCT116 xenograft model was also observed. These data indicate that 11w is a promising covalent inhibitor of FAK.

Noncovalent EGFR T790M/L858R inhibitors based on diphenylpyrimidine scaffold: Design, synthesis, and bioactivity evaluation for the treatment of NSCLC

A series of diphenylpyrimidine derivatives bearing a hydroxamic acid group was designed and synthesized as noncovalent EGFRT790M/L858R inhibitors to improve the biological activity and selectivity. One of the most promising compound 9d effectively interfered EGFRT790M/L858R binding with ATP and suppressed the proliferation of H1975 cells with IC50 values of 1.097 nM and 0.09777 μM, respectively. Moreover, compound 9d also not only exhibited a high selective index of 43.4 for EGFRT790M/L858R over the wild-type and 10.9 for H1975 cells over A431, but also exhibited low toxicity against the normal HBE cells (IC50 > 20 μΜ). In addition, the action mechanism validated that compound 9d effectively inhibited cell migration and promoted cell apoptosis by blocking cell cycle at G2/M stage. Furthermore, the target dose-dependently downregulated the expression of p-EGFR and arrested the activation of downstream Akt and ERK in H1975. All these studies provide important clues for the discovery of potent noncovalent EGFRT790M/L858R inhibitors.

Aminodithioformate compound used as FAK inhibitor

A purpose of the invention is to provide an aminodithioformate compound serving as an FAK inhibitor, a pharmaceutical composition, a preparation method and applications thereof, wherein the compound has a structure represented by the following general formula (I).

Aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative as well as preparation and application of 2, 4-diarylaminopyrimidine derivative

The invention relates to an aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative represented by a general formula I, an optical isomer, a pharmaceutically acceptable salt, a solvate or a prodrug thereof, preparation methods of the aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative and the optical isomer, the pharmaceutically acceptable salt, the solvate or the prodrug, and a pharmaceutical composition using the compound represented by the general formula I as an active component, wherein substituents R1, R2, R3, R4, R5, R6, X, Y and Z have meanings given inthe specification. The invention also relates to the compound shown in the general formula I, which has strong ALK and ROS1 kinase inhibition effects, and also relates to application of the compound and the optical isomer and pharmaceutically acceptable salt thereof in preparation of drugs for treatment and/or prevention of diseases caused by ALK and ROS1 abnormal expression, and application of the compound in preparation of drugs for prevention of diseases caused by ALK and ROS1 abnormal expression. Use in particular in the preparation of a medicament for treatment and/or for preventing cancer

Design and synthesis of diphenylpyrimidine derivatives (DPPYs) as potential dual EGFR T790M and FAK inhibitors against a diverse range of cancer cell lines

A new class of pyrimidine derivatives were designed and synthesized as potential dual FAK and EGFRT790M inhibitors using a fragment-based drug design strategy. This effort led to the identification of the two most active inhibitors, namely 9a and 9f, against both FAK (IC50 = 1.03 and 3.05 nM, respectively) and EGFRT790M (IC50 = 3.89 and 7.13 nM, respectively) kinase activity. Moreover, most of these compounds also exhibited strong antiproliferative activity against the three evaluated FAK-overexpressing pancreatic cancer (PC) cells (AsPC-1, BxPC-3, Panc-1) and two drug-resistant cancer cell lines (breast cancer MCF-7/adr cells and lung cancer H1975 cells) at concentrations lower than 6.936 μM. In addition, 9a was also effective in the in vivo assessment conducted in a FAK-driven human AsPC-1 cell xenograft mouse model. Overall, this study offers a new insight into the treatment of hard to treat cancers.

Pyrroformyl-containing 2,4-diaminopyrimidine derivatives as a new optimization strategy of ALK inhibitors combating mutations

Aiming to identify new optimization strategy effective for ALK-mutations, two series of pyrroformyl-containing 2,4-diaminopyrimidine compounds (11a-o, 12a-o) were designed, synthesized and evaluated for their anti-proliferative activities against three ca

Design, Synthesis, and Biological Evaluation of Covalent Inhibitors of Focal Adhesion Kinase (FAK) against Human Malignant Glioblastoma

Human malignant glioblastoma (GBM) is a highly invasive and lethal brain tumor. Targeting of integrin downstream signaling mediators in GBM such as focal adhesion kinase (FAK) seems reasonable and recently demonstrated promising results in early clinical

Compounds for targeted degradation of focal adhesion kinase and application of the compounds in medicine

The invention relates to the field of biomedicine and drug synthesis, in particular to compounds for targeted degradation of focal adhesion kinase (FAK) protein, pharmaceutically acceptable salts, hydrates, solvates or prodrugs of the compounds, preparation methods of the compounds and the pharmaceutically acceptable salts, hydrates, solvates or prodrugs, and application of the compounds as therapeutic agents, especially as FAK degradation agents. The structures of the compounds, and the geometric isomers or pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof are shown inthe specification. The compounds provided by the invention have a good degradation effect on FAK kinase, and can be used for preventing, treating or adjunctively treating various diseases related tothe expression or activity of FAK kinase.