855765-21-8

Upstream product

• 141-82-2 malonic acid 
• 536-90-3 m-Anisidine 

Downstream Products

• 55934-21-9 2,4-dichloro-5-methoxyquinoline 
• 55934-22-0 2,4-dichloro-7-methoxyisoquinoline 

Relevant academic research and scientific papers

Hepatitis C virus inhibitors

Hepatitis C virus inhibitors having the general formula (I) are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

Syntheses and fluorescent properties of 6-methoxy-2-oxoquinoline-3,4- dicarbonitriles and 6,7-dimethoxy-2-oxoquinoline-3,4-dicarbonitriles

4-Chlorocarbostyrils 3, 12, 17, 24, 26 with methoxy substituents in 6, 7, or 6,7-position react with potassium cyanide in a p-toluenesulfinate mediated reaction either to the highly fluorescent and stable 2-oxoquinoline-3,4- dicarbonitriles 6, 27, 29, 30 or at slightly lower temperatures to 4-monocarbonitriles 5, 13, 18. 4-Chlorocarbostyril 3 and lithium p-toluenesulfinate gave pure 4-toluenesulfonylquinolone 4, which reacted with potassium cyanide either to monocarbonitrile 5 or dicarbonitrile 6, depending on the reaction conditions. 4-Trifluoromethylquinolones 9 and 19 were prepared for fluorescence comparison from the appropriate methoxyaniline and 4,4,4-trifluoroacetoacetate. The fluorescence properties such as emission wavelengths and quantum yields of 6-methoxyderivatives 4, 5, 6, 9, 13 were studied and compared with those of 7-methoxy derivatives 18, 19 and 6,7-dimethoxyderivatives 27, 28, 29, 30. 6,7-Dimethoxy derivatives show best results, showing long-waved fluorescence spectra up to 520 nm and acceptable quantum yields up to 0.46 for 3,4-dicyano derivative 27 excited at 440 nm in acetonitrile.

Discovery and biological activity of 6BrCaQ as an inhibitor of the Hsp90 protein folding machinery

Heat shock protein90 (Hsp90) is a significant target in the development of rational cancer therapy, due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and viability. Here, a novel series of Hsp90 inhibitors containing a quinolein-2-one scaffold was synthesized and evaluated in cell proliferation assays. Results from these structure-activity relationships studies enabled identification of the simplified 3-aminoquinolein-2-one analogue 2b (6BrCaQ), which manifests micromolar activity against a panel of cancer cell lines. The molecular signature of Hsp90 inhibition was assessed by depletion of standard known Hsp90 client proteins. Finally, processing and activation of caspases 7, 8, and 9, and the subsequent cleavage of PARP by 6BrCaQ, suggest stimulation of apoptosis through both extrinsic and intrinsic pathways. Hot stuff! A novel series of Hsp90 inhibitors containing a quinolein-2-one scaffold was synthesized and screened in cell proliferation assays. The most potent inhibitor, 6BrCaQ, exhibited strong antiproliferative activity against a panel of cancer cell lines and resulted in downregulation of Hsp90 client proteins. Moreover, 6BrCaQ induced a high level of apoptosis in MCF-7 breast cancer cells, and was found to mediate cell death in a p23-independent manner.