85276-41-1

Upstream product

• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 6277-38-9 1-(4-methoxy-3-nitrophenyl)ethanone 
• 6318-64-5 1-(3-amino-4-methoxyphenyl)ethan-1-one 

Downstream Products

• 85276-46-6 5-acetyl-2-methoxybenzenesulfonamide 
• 70958-56-4 5-<1-hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl>-2-methoxy-N-methylbenzenesulfonamide 
• 344754-74-1 5-{2-[Benzyl-(1-methyl-3-phenyl-propyl)-amino]-acetyl}-2-methoxy-N-methyl-benzenesulfonamide 
• 345948-61-0 5-{2-[Benzyl-(1-methyl-2-phenoxy-ethyl)-amino]-acetyl}-2-hydroxy-benzenesulfonamide 
• 344754-71-8 5-{2-[Benzyl-(1-methyl-3-phenyl-propyl)-amino]-1-hydroxy-ethyl}-2-methoxy-N-methyl-benzenesulfonamide 
• 345948-60-9 5-{2-[Benzyl-(1-methyl-2-phenoxy-ethyl)-amino]-1-hydroxy-ethyl}-2-hydroxy-benzenesulfonamide 
• 345649-09-4 2-Hydroxy-5-[1-hydroxy-2-(1-methyl-2-phenoxy-ethylamino)-ethyl]-benzenesulfonamide 
• 85276-60-4 5-(2-Bromo-acetyl)-2-methoxy-N-methyl-benzenesulfonamide 
• 85276-53-5 5-acetyl-2-methoxy-N-methylbenzenesulfonamide 

Relevant academic research and scientific papers

New chalcone-sulfonamide hybrids exhibiting anticancer and antituberculosis activity

New sulfonamides 5/6 derived from 4-methoxyacetophenone 1 were synthesized by N-sulfonation reaction of ammonia (3)and aminopyrimidinone (4)with its sulfonyl chloride derivative 2. Sulfonamides 5 and 6 were used as precursors of two new series of chalcones 8a-f and 9a-f, which were obtained through Claisen-Schmidt condensation with aromatic aldehydes 7a-f. Compounds 5/6, 8a-d, 8f, 9a-d, and 9f were screened by the US National Cancer Institute (NCI)at 10 μM against sixty different human cancer cell lines (one-dose trial). Chalcones 8b and 9b satisfied the pre-determined threshold inhibition criteria and were selected for screening at five different concentrations (100, 10, 1.0, 0.1, and 0.01 μM). Compound 8b exhibited remarkable GI50 values ranging from 0.57 to 12.4 μM, with cytotoxic effects being observed in almost all cases, especially against the cell lines K-562 of Leukemia and LOX IMVI of Melanoma with GI50 = 0.57 and 1.28 μM, respectively. Moreover, all compounds were screened against Mycobacterium tuberculosis H37Rv, chalcones 8a-c and 9a-c were the most active showing MIC values between 14 and 42 μM, and interestingly they were devoid of antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus. These antituberculosis hits showed however low selectivity, being equally inhibitory to M. tuberculosis and mammalian T3T cells. The chalcone-sulfonamide hybrids 8a-f and 9a-f resulted to be appealing cytotoxic agents with significant antituberculosis activity.

Fragment-based drug discovery of 2-thiazolidinones as BRD4 inhibitors: 2. Structure-based optimization

The signal transduction of acetylated histone can be processed through a recognition module, bromodomain. Several inhibitors targeting BRD4, one of the bromodomain members, are in clinical trials as anticancer drugs. Hereby, we report our efforts on discovery and optimization of a new series of 2-thiazolidinones as BRD4 inhibitors along our previous study. In this work, guided by crystal structure analysis, we reversed the sulfonamide group and identified a new binding mode. A structure-activity relationship study on this new series led to several potent BRD4 inhibitors with IC50 of about 0.05-0.1 μM in FP binding assay and GI50 of 0.1-0.3 μM in cell based assays. To complete the lead-like assessment of this series, we further checked its effects on BRD4 downstream protein c-Myc, investigated its selectivity among five different bromodomain proteins, as well as the metabolic stability test, and reinforced the utility of 2-thiazolidinone scaffold as BET bromodomain inhibitors in novel anticancer drug development.