25030-31-3

Usage

Uses

Used in Pharmaceutical Research:
Adenosine, 5'-sulfaMate is used as a research tool for the development of novel parasite inhibitors. It has potential applications in the design and synthesis of β-ketosulfonamide adenylation inhibitors, which are being studied for their antitubercular antibiotic properties.
Used in Antitubercular Drug Development:
Adenosine, 5'-sulfaMate is used in the design and synthesis of β-ketosulfonamide adenylation inhibitors, which are being studied as potential antitubercular antibiotics. These inhibitors may offer new treatment options for tuberculosis and other related diseases.

Upstream product

• 112921-00-3 ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl sulfamate 
• 362-75-4 2',3'-isopropylidene adenosine 
• 58-61-7 adenosine 
• 64-17-5 ethanol 
• 1356085-18-1 6-N-benzyloxycarbonyl-2',3'-O-benzylidene-5'-O-[N-(N-Cbz-L-valinyl)sulfamoyl]adenosine 
• 1356085-21-6 6-N-benzyloxycarbonyl-2',3'-O-benzylidene-5'-O-[N-(N-Cbz-L-lysinyl(ε-Cbz))sulfamoyl]adenosine 
• 1356085-27-2 6-N-benzyloxycarbonyl-2',3'-O-benzylidene-5'-O-[N-(N-Cbz-L-ornithinyl(δ-Cbz))-sulfamoyl]adenosine 
• 1356085-30-7 6-N-benzyloxycarbonyl-2',3'-O-benzylidene-5'-O-[N-(N-Cbz)-L-homoserinyl(OBn)sulfamoyl]adenosine 
• 146-77-0 2-Chloroadenosine 
• 64911-28-0 O^2'_,O3'_,O5'-tris-(tert-butyl-dimethyl-silanyl)-adenosine 
• 69504-15-0 2',3'-O,O-bis(t-butyldimethylsilyl)adenosine 
• 863238-53-3 2',3'-O-bis(tert-butyldimethylsilyl)-5'-O-(sulfamoyl)adenosine 

Relevant academic research and scientific papers

Synthesis, structure and bioactivity of primary sulfamate-containing natural products

Here we report the synthesis of natural products (NPs) 5′-O-sulfamoyl adenosine 1 and 5′-O-sulfamoyl-2-chloroadenosine 2. As primary sulfamates these compounds represent an uncommon class of NPs, furthermore there are few NPs known that contain a N–S bond. Compounds 1 and 2 were evaluated for inhibition of carbonic anhydrases (CA), a metalloenzyme family where the primary sulfamate is known to coordinate to the active site zinc and form key hydrogen bonds with adjacent CA active site residues. Both NPs were good to moderate CA inhibitors, with compound 2 a 20–50-fold stronger CA inhibitor (Ki values 65–234 nM) than compound 1. The protein X-ray crystal structures of 1 and 2 in complex with CA II show that it is not the halogen-hydrophobic interactions that give compound 2 a greater binding energy but a slight movement in orientation of the ribose ring that allows better hydrogen bonds to CA residues. Compounds 1 and 2 were further investigated for antimicrobial activity against a panel of microbes relevant to human health, including Gram-negative bacteria (4 strains), Gram-positive bacteria (1 strain) and yeast (2 strains). Antimicrobial activity and selectivity was observed. The minimum inhibitory concentration (MIC) of NP 1 was 10 μM against Gram-positive Staphylococcus aureus and NP 2 was 5 μM against Gram-negative Escherichia coli. This is the first time that NP primary sulfamates have been assessed for inhibition and binding to CAs, with systematic antimicrobial activity studies also reported.

Investigation, optimization and synthesis of sulfamoyloxy-linked aminoacyl-AMP analogues

Aminoacyl-tRNA synthetases (aaRSs) constitute a family of enzymes that transfer amino acids to their corresponding tRNA molecules to form aminoacyl-tRNAs and have been validated as potential drug targets. Sulfamoyloxy-linked aminoacyl-AMP analogues are potent inhibitors of aaRSs. In this article, we report the synthesis of several new sulfamoyl analogues of aa-AMP that up to now have been difficult or even impossible to prepare with current synthetic strategies. The developed synthetic strategy relies on performing the synthesis under neutral conditions followed by global deprotection using catalytic hydrogenation affording the desired 5′-O-(N-aminoacyl)sulfamoyladenosine compounds.

Identification of NAE inhibitors exhibiting potent activity in leukemia cells: Exploring the structural determinants of NAE specificity

MLN4924 is a selective inhibitor of the NEDD8-activating enzyme (NAE) and has advanced into clinical trials for the treatment of both solid and hematological malignancies. In contrast, the structurally similar compound 1 (developed by Millennium: The Takeda Oncology Company) is a pan inhibitor of the E1 enzymes NAE, ubiquitin activating enzyme (UAE), and SUMO-activating enzyme (SAE) and is currently viewed as unsuitable for clinical use given its broad spectrum of E1 inhibition. Here, we sought to understand the determinants of NAE selectivity. A series of compound 1 analogues were synthesized through iterative functionalization of the purine C6 position and evaluated for NAE specificity. Optimal NAE specificity was achieved through substitution with primary N-alkyl groups, while bulky or secondary N-alkyl substituents were poorly tolerated. When assessed in vitro, inhibitors reduced the growth and viability of malignant K562 leukemia cells. Through this study, we have successfully identified a series of sub-10 nM NAE-specific inhibitors and thereby highlighted the functionalities that promote NAE selectivity.

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.