406231-90-1

Upstream product

• 1356496-20-2 4-(4,4-dimethyl-piperidin-1-yl)-thiobenzoic acid S-(9H-fluoren-9-ylmethyl) ester 
• 1069135-23-4 C₁₄H₁₃N₅O₄S₂ 
• 1069135-26-7 C₁₄H₁₉NOS 
• 1493-27-2 ortho-nitrofluorobenzene 
• 2014-75-7 2-(phenylthio)ethanamine 
• 4160-82-1 3,3-dimethylglutaric anhydride 
• 279692-22-7 4-(4-carboxy-3,3-dimethyl-butyrylamino)-benzoic acid ethyl ester 
• 279692-23-8 ethyl 4-(4,4-dimethyl-2,6-dioxopiperidin-1-yl)benzoate 
• 406233-25-8 ethyl 4-(4,4-dimethylpiperidin-1-yl)benzoate 
• 406233-31-6 4-fluoro-3-nitrobenzenesulfonamide 
• 406233-26-9 4-(4,4-dimethylpiperidin-1-yl)benzoic acid 
• 406233-13-4 3-nitro-4-(2-phenylsulfanylethylamino)-benzenesulfonamide 
• 6668-56-0 4-fluoro-3-nitrobenzene-1-sulfonyl chloride 
• 94-09-7 p-aminoethylbenzoate 

Relevant academic research and scientific papers

ACYLSULFONAMIDES AND PROCESSES FOR PRODUCING THE SAME

The present disclosure relates to acylsulfonamides and processes for their preparation. The processes involve a target-guided synthesis approach, whereby a thioacid and a sulfonyl azide are reacted in the presence of a biological target protein, a Bcl-2 family protein, to form the acylsulfonamide.

Sulfo-click reaction via in situ generated thioacids and its application in kinetic target-guided synthesis

Herein, we describe a practical, one-pot variant of the sulfo-click reaction, in which 9-fluorenylmethyl-protected thioesters are rapidly deprotected and reacted further with sulfonylazides to give N-acyl sulfonamides.

Bcl-XL-templated assembly of its own protein-protein interaction modulator from fragments decorated with thio acids and sulfonyl azides

Protein-protein interactions have key importance in various biological processes and modulation of particular protein-protein interactions has been shown to have therapeutic effects. However, disrupting or modulating protein-protein interactions with low-molecular-weight compounds is extremely difficult due to the lack of deep binding pockets on protein surfaces. Herein we describe the development of an unprecedented lead synthesis and discovery method that generates only biologically active compounds from a library of reactive fragments. Using the protein Bcl-XL, a central regulator of programmed cell death, we demonstrated that an amidation reaction between thio acids and sulfonyl azides is applicable for Bcl-XL-templated assembly of inhibitory compounds. We have demonstrated for the first time that kinetic target-guided synthesis can be applied not only on enzymatic targets but also for the discovery of small molecules modulating protein-protein interactions. Copyright

Discovery and structure-activity relationship of antagonists of B-cell lymphoma 2 family proteins with chemopotentiation activity in vitro and in vivo

Development of a rationally designed potentiator of cancer chemotherapy, via inhibition of Bcl-XL function, is described. Lead compounds generated by NMR screening and directed parallel synthesis displayed sub-μM binding but were strongly deactivated in the presence of serum. The dominant component of serum deactivation was identified as domain III of human serum albumin (HSA); NMR solution structures of inhibitors bound to both Bcl-X L and HSA domain III indicated two potential optimization sites for separation of affinities. Modifications at both sites resulted in compounds with improved Bcl-XL binding and greatly increased activity in the presence of human serum, culminating in 73R, which bound to Bcl-XL with a Ki of 0.8 μM. In a cellular assay 73R reversed the protection afforded by Bcl-XL overexpression against cytokine deprivation in FL5.12 cells with an EC50 of 0.47 μM. 73R showed little effect on the viability of the human non small cell lung cancer cell line A549. However, consistent with the proposed mechanism, 73R potentiated the activity of paclitaxel and UV irradiation in vitro and potentiated the antitumor efficacy of paclitaxel in a mouse xenograft model.