3400-29-1

Upstream product

• 41106-02-9 α-(2-nitrophenyl)-N-methylnitrone 
• 108-24-7 acetic anhydride 
• 593-51-1 methylamine hydrochloride 
• 610-14-0 2-nitrobenzyl chloride 
• 552-16-9 ortho-nitrobenzoic acid 
• 74-89-5 methylamine 
• 606-27-9 methyl 2-nitrobenzoate 
• 6154-14-9 N-chloromethylamine 
• 552-89-6 2-nitro-benzaldehyde 

Downstream Products

• 123534-30-5 1-(4'-methylphenylsulfonyl)-2,1-benzisoxazol-3(1H)-one 
• 607-19-2 3-methyl-2,4(1H,3H)-quinazolinedione 
• 4141-08-6 2-Amino-N-methylbenzamid 
• 1439356-99-6 ethyl 6,7,8-trifluoro-1-methyl-4-oxo-2-(2-nitrophenyl)-1,4-dihydroquinoline-3-carboxylate 
• 761440-08-8 2-[(2,5-dichloropyrimidin-4-yl)amino]-N-methyl-benzamide 
• 1022964-14-2 2-[(2-chloro-5-methylpyrimidin-4-yl)amino]-N-methylbenzamide 
• 1257993-70-6 N-(3-((5-chloro-2-((4-((diethoxyphosphoryl)methy))amino)phenylamino-4-pyrimidinyl)amino)phenyl)-N-methylbenzamide 

Relevant academic research and scientific papers

A one-pot transition-metal-free tandem process to 1,4-benzodiazepine scaffolds

An efficient and practical method for the synthesis of 1,4-benzodiazepines is reported. This methodology offers a transition-metal-free tandem process in one pot. This process is applicable to the construction of a wide variety of 1,4-benzodiazepines and other tricyclic systems with high potential biological and pharmacological activities. Georg Thieme Verlag Stuttgart · New York.

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).

Rhodium-Catalyzed Electrooxidative C?H Olefination of Benzamides

Metal-catalyzed chelation-assisted C?H olefinations have emerged as powerful tools for the construction of functionalized alkenes. Herein, we describe the rhoda-electrocatalyzed C?H activation/alkenylation of arenes. The olefinations of challenging electron-poor benzamides were thus accomplished in a fully dehydrogenative fashion under electrochemical conditions, avoiding stoichiometric chemical oxidants, and with H2 as the only byproduct. This versatile alkenylation reaction also features broad substrate scope and used electricity as a green oxidant.

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.

Discovery of 7H-pyrrolo[2,3-d]pyridine derivatives as potent FAK inhibitors: Design, synthesis, biological evaluation and molecular docking study

Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase responsible for development of various tumor types. Aiming to explore new potent inhibitors, two series of 2,4-disubstituted-7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized on the base of structure-based design strategy. Biological evaluation indicated that most of these new compounds could potently inhibit FAK kinase, leading to the promising inhibitors against the proliferation of U-87MG, A-549, and MDA-MB-231 cancer cell lines. Among them, the optimized compound 18h potently inhibited the enzyme (IC50 = 19.1 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC50 values of 0.35, 0.24, and 0.34 μM, respectively. Compound 18h is a multi-target kinase inhibitor. Furthermore, compound 18h also exhibited relatively less cytotoxicity (IC50 = 3.72 μM) toward a normal human cell line, HK2. According to the flow cytometry and wound healing assay results, compound 18h effectively induced apoptosis and G0/G1 phase arrest of MDA-MB-231 cells and suppressed the migration of U-87MG, A-549 and MDA-MB-231 cells. The docking study of compound 18h was performed to elucidate its possible binding modes and to provide a structural basis for the further structural guidance design of FAK inhibitors. Collectively, these data support the further development of compound 18h as a lead compound for FAK-targeted anticancer drug discovery.

Discovery of 2,4-diarylaminopyrimidine derivatives bearing dithiocarbamate moiety as novel FAK inhibitors with antitumor and anti-angiogenesis activities

A series of 2,4-diarylaminopyrimidine derivatives containing dithiocarbamate moiety were designed by molecular hybridization strategy and synthesized for screening as inhibitors of focal adhesion kinase (FAK). Most of these compounds exhibit significant a

Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells

A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC50 = 5.17 nM) and 7f (IC50 = 2.58 nM) displayed equal anti-FAK enzymatic activity to the lead compound TAE226 (6.79 nM). In particular, compound 7a also exhibited strong antiproliferative activity against several stubborn cancer cells, including AsPC-1 cells (IC50 = 0.105 μM), BxPC-3 cells (IC50 = 0.090 μM), and MCF-7/ADR cells (IC50 = 0.59 μM). Additionally, compound 7a also showed great antitumor efficacy in vivo via aAsPC-1 cancer Xenograft mouse model. The preliminary mechanism study by Western blot analysis revealed that 7a repressed FAK phosphorylation in AsPC cancer cells. Taken together, the results indicate that compound 7a may serve as a promising preclinical candidate for treatment of stubborn cancers.

Design, synthesis and biological evaluation of sulfonamide-substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity

A class of sulfonamide-substituted diphenylpyrimidines (Sul-DPPYs) were synthesized to improve activity against the focal adhesion kinase (FAK). Most of these new Sul-DPPYs displayed moderate activity against the FAK enzyme with IC50 values of less than 100?nM; regardless, they could effectively inhibit several classes of refractory cancer cell lines with IC50 values of less than 10?μM, including the pancreatic cancer cell lines (AsPC-1, Panc-1 and BxPC-3), the NSCLC-resistant H1975 cell line, and the B lymphocyte cell line (Ramos cells). Results of flow cytometry indicated that inhibitor 7e promoted apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, it almost completely induced the apoptosis at a concentration of 10?μM. Compound 7e may be selected as a potent FAK inhibitor for the treatment of pancreatic cancer.

Phosphamide-containing diphenylpyrimidine analogues (PA-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with enhanced activity against pancreatic cancer cell lines

A family of phosphamide-containing diphenylpyrimidine analogues (PA-DPPYs) were synthesized as potent focal adhesion kinase (FAK) inhibitors. The PA-DPPY derivatives could significantly inhibit the FAK enzymatic activity at concentrations lower than 10.69 nM. Among them, compounds 7a and 7e were two of the most active FAK inhibitors, possessing IC50 values of 4.25 nM and 4.65 nM, respectively. In particular, compound 7e also displayed strong activity against AsPC cell line, with an IC50 of 1.66 μM, but show low activity against the normal HPDE6-C7 cells (IC50 > 20 μM), indicating its low cell cytotoxicity. Additionally, flow cytometry analysis showed that after treatment with 7e (8 μM, 72 h), both AsPC and Panc cells growth were almost totally inhibited, with a cell viability rate of 16.8% and 18.1%, respectively. Overall, compound 7e may be served as a valuable FAK inhibitor for the treatment of pancreatic cancer.

Novel pyrimidine anti-tumor compound and preparation method and application thereof

The invention relates to a novel pyrimidine anti-tumor compound and a preparation method and application thereof. The novel pyrimidine anti-tumor compound is a compound shown in a formula (I), wherein each substituted group in the formula (I) is defined in the description. The invention also relates to the compound shown in the formula (I) or a pharmaceutically acceptable salt thereof, or application of a medicine composition containing the compound in inhibiting focal adhesion kinase, further treating tumor diseases, and especially treating pancreatic cancers, lung cancers and breast cancers. The formula (I) is shown in the description.