863238-54-4

Upstream product

• 58-61-7 adenosine 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 69504-15-0 2',3'-O,O-bis(t-butyldimethylsilyl)adenosine 
• 863238-53-3 2',3'-O-bis(tert-butyldimethylsilyl)-5'-O-(sulfamoyl)adenosine 
• 347370-91-6 (1H-benzo[d][1,2,3]triazol-1-yl)(2-hydroxyphenyl)methanone 
• 64911-28-0 O^2'_,O3'_,O5'-tris-(tert-butyl-dimethyl-silanyl)-adenosine 

Relevant academic research and scientific papers

Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice

Mycobactin biosynthesis in Mycobacterium tuberculosis facilitates iron acquisition, which is required for growth and virulence. The mycobactin biosynthesis inhibitor salicyl-AMS [5=-O-(N-salicylsulfamoyl)adenosine] inhibitsM. tuberculosis growth in vitro under iron-limited conditions. Here, we conducted a single-dose pharmacokinetic study and a monotherapy study of salicyl- AMS with mice. Intraperitoneal injection yielded much better pharmacokinetic parameter values than oral administration did. Monotherapy of salicyl-AMS at 5.6 or 16.7 mg/kg significantly inhibitedM. tuberculosis growth in the mouse lung, providing the first in vivo proof of concept for this novel antibacterial strategy. Copyright

ANTI-MICROBIAL AGENTS AND USES THEREOF

Many pathogens, including Mycobacterium tuberculosis and Yersinia pestis, rely on an iron acquisition system based on siderophores, secreted iron-chelating compounds with extremely high Fe(III) affinity. The compounds of the invention are inhibitors of domain salicylation enzymes, which catalyze the salicylation of an aroyl carrier protein (ArCP) domain to form a salicyl-ArCP domain thioester intermediate via a two-step reaction. The compounds include the intermediate mimic 5 '-O- [N- (salicyl)sulfamoyl] -adenosine (salicyl-AMS) and analogs thereof. These compounds are inhibitors of the salicylate activity of MbtA, YbtE, PchD, and other domain salicylation enzymes involved in the biosynthesis of siderophores. Therefore, these compounds may be used in the treatment of infection caused by microorganisms which rely on siderphore-based iron acquisition systems. Pharmaceutical composition and methods of using these compounds to treat or prevent infection are also provided as well as methods of preparing the inventive compounds.