3430-14-6Relevant articles and documents
Process Development and Protein Engineering Enhanced Nitroreductase-Catalyzed Reduction of 2-Methyl-5-nitro-pyridine
Bornadel, Amin,Bisagni, Serena,Pushpanath, Ahir,Slabu, Iustina,Lepaih, Jacques,Cherney, Alan H.,Mennen, Steven M.,Hedley, Simon J.,Tedrow, Jason,Dominguez, Beatriz
, p. 648 - 653 (2021)
Reduction of aromatic nitro compounds to anilines is of great interest to the chemical industry. Biocatalytic reduction of nitroarenes has made it possible to effectively produce anilines by applying nitroreductase enzymes (NR) in combination with vanadium pentoxide. Herein, the NR-catalyzed reduction of 2-methyl-5-nitro-pyridine (2) to give the desired aniline (1) was studied as a model reaction. It demonstrates the importance of process development and enzyme engineering as key approaches to overcome scale-up issues and improve yield and productivity. Moving to fed-batch allowed controlling the feeding rate of 2 to prevent the accumulation of intermediates and formation of undesired side products. Starting with a substrate (2) concentration of 200 mM (28 g/L) and enzyme loading of 5 mg/mL (18% w/w), it was possible to achieve complete conversion and 1 in 95% yield by high-performance liquid chromatography (89.1% isolated yield) over 18 h, whereas, with 500 mM (69 g/L) 2 and an enzyme loading of 10 mg/mL (14.5% w/w), the same conversion and yield were achieved in 26 h. A rational engineering of NR-4 yielded faster variants, including NR-5, in only one round. The improved rate of the new variants allowed increasing the feeding rate of 2 to shorten the reaction time to less than a day as well as decreasing the enzyme loading to 3.6%.
ARYL-SULFONAMIDE AND ARYL-SULFONE DERIVATIVES AS TRPML MODULATORS
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Page/Page column 55, (2018/12/03)
The new arylsulfonamide and arylsulfone derivatives are modulators of TRPML and are useful in treating disorders related to TRPML activities and lysosome functions such as acid-related disorders and cancer.
Methods of treating cytokine mediated diseases
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, (2008/06/13)
Disclosed are methods of treating certain cytokine mediated diseases or conditions using novel aromatic heterocyclic compounds of the formula(I) wherein Ar1,Ar2,L,Q and X are described herein.