1598417-70-9

Upstream product

• 403-21-4 3-fluoro-4-nitrobenzoic acid 
• 87120-72-7 1-(tert-butoxycarbonyl)-4-aminopiperidine 
• 157665-51-5 3-fluoro-4-nitrobenzoyl chloride 

Downstream Products

• 1598417-71-0 3-fluoro-4-nitro-N-piperidin-4-yl-benzamide hydrochloride 

Relevant academic research and scientific papers

Design, synthesis, biological evaluation and molecular docking study of novel thieno[3,2-d]pyrimidine derivatives as potent FAK inhibitors

A series of 2,7-disubstituted-thieno[3,2-d]pyrimidine derivatives were designed, synthesized and evaluated as novel focal adhesion kinase (FAK) inhibitors. The novel 2,7-disubstituted-thieno[3,2-d]pyrimidine scaffold has been designed as a new kinase inhibitor platform that mimics the bioactive conformation of the well-known diaminopyrimidine motif. Most of the compounds potently suppressed the enzymatic activities of FAK and potently inhibited the proliferation of U-87MG, A-549 and MDA-MB-231 cancer cell lines. Among these derivatives, the optimized compound 26f potently inhibited the enzyme (IC50 = 28.2 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC50 values of 0.16, 0.27, and 0.19 μM, respectively. Compound 26f also exhibited relatively less cytotoxicity (IC50 = 3.32 μM) toward a normal human cell line, HK2. According to the flow cytometry results, compound 26f induced the apoptosis of MDA-MB-231 cells in a dose-dependent manner and effectively arrested MDA-MB-231 cells in G0/G1 phase. Further investigations revealed that compound 26f potently suppressed the migration of MDA-MB-231 cells. Collectively, these data support the further development of compound 26f as a lead compound for FAK-targeted anticancer drug discovery.

Design, synthesis and biological evaluation of novel 7H-pyrrolo[2,3-d]pyrimidine derivatives as potential FAK inhibitors and anticancer agents

A series of 7H-pyrrolo[2,3-d]pyrimidine derivatives possessing a dimethylphosphine oxide moiety were designed, synthesized and evaluated as novel Focal adhesion kinase (FAK) inhibitors. Most compounds potently suppressed the enzymatic activities of FAK, with IC50 values in the 10?8–10?9 M range, and potently inhibited the proliferation of breast (MDA-MB-231) and lung (A549) cancer cell lines. The representative compound 25b exhibited potent enzyme inhibition (IC50 = 5.4 nM) and good selectivity when tested on a panel of 26 kinases. 25b exhibited antiproliferative activity against A549 cells (IC50 = 3.2 μM) and relatively less cytotoxicity to a normal human cell line HK2. Compound 25b also induced apoptosis and suppressed the migration of A549 cells in a concentration-dependent manner. Further profiling of compound 25b revealed it had good metabolic stability in mouse, rat and human liver microsomes in vitro and showed weak inhibitory activity against various subtypes of human cytochrome P450. The docking study of compound 25b was performed to elucidate its possible binding modes and to provide a structural basis for further structure-guided design of FAK inhibitors.

INHIBITORS OF DNA GYRASE FOR THE TREATMENT OF BACTERIAL INFECTIONS

The present invention relates to compounds which specifically inhibit bacterial DNA Gyrase and can be used for the treatment of respiratory tract infections.