677727-35-4

Upstream product

• 501-53-1 benzyl chloroformate 
• 98-18-0 m-aminobenzenesulfonamide 

Downstream Products

• 1449004-73-2 N-(3-(N-(L-leucyl)sulfamoyl)phenylcarbamothioyl)-4-methoxybenzenamide 
• 1449004-72-1 N-(3-(N-(L-leucyl)sulfamoyl)phenylcarbamothioyl)-3-methoxybenzenamide 
• 1449004-71-0 N-(3-(N-(L-leucyl)sulfamoyl)phenylcarbamothioyl)-benzenamide 

Relevant academic research and scientific papers

Design and synthesis of N-(3-sulfamoylphenyl)amides as Trypanosoma brucei leucyl-tRNA synthetase inhibitors

The protozoan parasite Trypanosoma brucei (T. brucei) causes human African trypanosomiasis (HAT), which is a fatal and neglected disease in the tropic areas, and new treatments are urgently needed. Leucyl-tRNA synthetase (LeuRS) is an attractive target for the development of antimicrobial agents. In this work, starting from the hit compound thiourea ZCL539, we designed and synthesized a series of amides as effective T. brucei LeuRS (TbLeuRS) synthetic site inhibitors. The most potent compounds 74 and 91 showed IC50 of 0.24 and 0.25 μM, which were about 700-fold more potent than the starting hit compound. The structure-activity relationship was also discussed. These compounds provided a new scaffold and lead compounds for further development of antitrypanosomal agents.

Design and synthesis of α-phenoxy-N-sulfonylphenyl acetamides as Trypanosoma brucei Leucyl-tRNA synthetase inhibitors

Human African trypanosomiasis (HAT), caused by the parasitic protozoa Trypanosoma brucei, is one of the fatal diseases in tropical areas and current medicines are insufficient. Thus, development of new drugs for HAT is urgently needed. Leucyl-tRNA synthetase (LeuRS), a recently clinically validated antimicrobial target, is an attractive target for development of antitrypanosomal drugs. In this work, we report a series of α-phenoxy-N-sulfonylphenyl acetamides as T. brucei LeuRS inhibitors. The most potent compound 28g showed an IC50 of 0.70 μM which was 250-fold more potent than the starting hit compound 1. The structure-activity relationship was also discussed. These acetamides provided a new scaffold and lead compounds for the further development of clinically useful antitrypanosomal agents.

Discovery of N-(4-sulfamoylphenyl)thioureas as Trypanosoma brucei leucyl-tRNA synthetase inhibitors

Human African trypanosomiasis (HAT) is one of the most neglected diseases in the tropic regions, which is fatal if not treated in time. There is an urgent need for new therapeutics, especially those in new chemical classes. Leucyl-tRNA synthetase (LeuRS) has been paid much attention as a recently clinically validated antimicrobial target. Our group has previously reported T. brucei LeuRS (TbLeuRS) inhibitors, including benzoxaboroles targeting the editing site and pyrrolinones targeting the synthetic site. Here we report the discovery of N-(4-sulfamoylphenyl)thioureas as a new class of TbLeuRS inhibitors. The R1 and R2 groups, reminiscent of the leucyl and adenyl regions of aa-AMP and aa-AMS, were optimized to result in a significant 13-fold increase of inhibitory activity (compound 19, IC 50 = 13.7 μM). Aided by ligand-protein docking, the 1,3-substitution at the central phenyl ring was predicted and proved to give significantly improved activity (59, IC50 = 1.1 μM). This work provided a new scaffold for the exploration of novel inhibitors against TbLeuRS, which may become potential therapeutics for the treatment of HAT.

BIFUNCTIONAL HETEROCYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME

The invention provides a family of bifunctional heterocyclic compounds useful as anti-infective, anti-proliferative, anti-inflammatory, and prokinetic agents. The invention also provides methods of making the bifunctional hetercyclic compounds, and methods of using such compounds as anti-infective, anti-proliferative agents, anti-inflammatory, and/or prokinetic agents.