273204-52-7

Upstream product

• 20718-78-9 2-Hydroxy-3-methoxy-5-nitrobenzoic acid 
• 877-22-5 3-methoxysalicylic acid 
• 6066-82-6 1-hydroxy-pyrrolidine-2,5-dione 
• 72517-20-5 2,3-dihydroxy-5-nitrobenzoic acid 

Downstream Products

• 1312944-63-0 1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-β-D-ribo-hept-5-enofuranosyl]-4-(trifluoromethyl)-1H-imidazole 
• 1312944-62-9 pyridin-4-yl (5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-1-thio-β-D-ribo-hept-5-enofuranoside 
• 1312944-61-8 1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-β-d-ribohept-5-enofuranosyl]pyridin-4-(1H)-one 
• 1312944-60-7 1-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-β-d-ribohept-5-enofuranosyl]benzo[d]imidazole 
• 1312944-65-2 9-[(5E)-5,6,7-trideoxy-7-(2,3-dihydroxy-5-nitrobenzamido)-β-D-ribo-hept-5-enofuranosyl]purine 
• 1312944-64-1 (2E)-4,7-anhydro-1,2,3-trideoxy-1-(2,3-dihydroxy-5-nitrobenzamido)-L-ribo-hept-2-enitol 
• 273204-60-7 N-(2-[{(2S,3R,4R,5R)-5-[4-(Benzoylamino)-6-oxo-1,6-dihydropyrimidin-1-yl]-3,4-dihydrotetrahydrofuran-2-yl}methoxy]ethyl)-2,3-dihydroxy-5-nitrobenzamide 
• 273204-57-2 (2S,3R,4R,5R)-2-[6-(Benzoylamino)purin-9-yl]-5-({2-[(2,3-dihydroxy-5-nitrobenzoyl)amino]ethoxy}methyl)tetrahydrofuran-3,4-diyl diacetate 
• 273204-59-4 (2S,3R,4R,5R)-2-[4-(Benzoylamino)-6-oxo-1,6-dihydropyrimidin-1-yl]-5-({2-[(2,3-dihydroxy-5-nitrobenzoyl)amino]ethoxy}methyl)tetrahydrofuran-3,4-diyl diacetate 
• 273204-58-3 (2S,3R,4R,5R)-2-[2-(Benzoylamino)-2-oxo-1,2-dihydropyrimidin-1-yl]-5-({2-[(2,3-dihydroxy-5-nitrobenzoyl)amino]ethoxy}methyl)tetrahydrofuran-3,4-diyl diacetate 

Relevant academic research and scientific papers

Molecular recognition at the active site of catechol-O-methyltransferase (COMT): Adenine replacements in bisubstrate inhibitors

L-Dopa, the standard therapeutic for Parkinson's disease, is inactivated by the enzyme catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of an activated methyl group from S-adenosylmethionine (SAM) to its catechol substrates, such as L-dopa, in the presence of magnesium ions. The molecular recognition properties of the SAM-binding site of COMT have been investigated only sparsely. Here, we explore this site by structural alterations of the adenine moiety of bisubstrate inhibitors. The molecular recognition of adenine is of special interest due to the great abundance and importance of this nucleobase in biological systems. Novel bisubstrate inhibitors with adenine replacements were developed by structure-based design and synthesized using a nucleosidation protocol introduced by Vorbrueggen and co-workers. Key interactions of the adenine moiety with COMT were measured with a radiochemical assay. Several bisubstrate inhibitors, most notably the adenine replacements thiopyridine, purine, N-methyladenine, and 6-methylpurine, displayed nanomolar IC50 values (median inhibitory concentration) for COMT down to 6 nM. A series of six cocrystal structures of the bisubstrate inhibitors in ternary complexes with COMT and Mg2+ confirm our predicted binding mode of the adenine replacements. The cocrystal structure of an inhibitor bearing no nucleobase can be regarded as an intermediate along the reaction coordinate of bisubstrate inhibitor binding to COMT. Our studies show that solvation varies with the type of adenine replacement, whereas among the adenine derivatives, the nitrogen atom at position 1 is essential for high affinity, while the exocyclic amino group is most efficiently substituted by a methyl group. Copyright

Structure-based design, synthesis, and in vitro evaluation of bisubstrate inhibitors for catechol O-methyltransferase (COMT)

The enzyme catechol O-methyltransferase (COMT) catalyzes the Me group transfer from the cofactor S-adenosylmethionine (SAM) to the hydroxy group of catechol substrates. Potential bisubstrate inhibitors of COMT were developed by structure-based design and synthesized. The compounds were tested for in vitro inhibitory activity against COMT obtained from rat liver, and the inhibition kinetics were examined with regard to the binding sites of cofactor and substrate. One of the designed molecules was found to be a bisubstrate inhibitor of COMT with an IC50 = 2 μM. It exhibits competitive kinetics for the SAM and noncompetitive kinetics for the catechol binding site. Useful structure-activity relationships were established which provide important guidelines for the design of future generations of bisubstrate inhibitors of COMT.