499796-71-3Relevant academic research and scientific papers
An improved Balz-Schiemann reaction enabled by ionic liquids and continuous processing
Snead, David R.,Lévesque, Fran?ois,Morris, William J.,Naber, John R.
, p. 4261 - 4265 (2019/05/24)
A Balz-Schiemann reaction was developed to convert 2-cyano-5-aminopyridine to 2-cyano-5-fluoropyridine. The use of an ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate, BMIMBF4) as a solvent was found to be critical in achieving high assay yields and high selectivity for the fluorination vs. protonation. A process was developed to recycle and reuse the ionic liquid enabling its cost-effective use as a solvent. Finally, the optimal conditions were demonstrated under as a continuous process to address process safety risks associated with diazonium intermediates and the product was used to access a key intermediate in the synthesis of β-amyloid cleaving enzyme 1 inhibitor, verubecestat.
CATHEPSIN CYSTEINE PROTEASE INHIBITORS
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Page/Page column 65; 66, (2015/04/28)
This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
CATHEPSIN CYSTEINE PROTEASE INHIBITORS
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Page/Page column 57; 65; 66, (2015/04/28)
This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.
Substrate-Specific Heterogeneous Catalysis of CeO2 by Entropic Effects via Multiple Interactions
Tamura, Masazumi,Sawabe, Kyoichi,Tomishige, Keiichi,Satsuma, Atsushi,Shimizu, Ken-Ichi
, p. 20 - 26 (2015/04/27)
Achieving complete substrate specificity through multiple interactions like an enzyme is one of the ultimate goals in catalytic studies. Herein, we demonstrate that multiple interactions between the CeO2 surface and substrates are the origin of substrate-specific hydration of nitriles in water by CeO2, which is exclusively applicable to the nitriles with a heteroatom (N or O) adjacent to the α-carbon of the CN group but is not applicable to the other nitriles. Kinetic studies reveal that CeO2 reduces the entropic barrier (TΔS?) for the reaction of the former reactive substrate, leading to 107-fold rate enhancement compared with the latter substrate. Density functional theory (DFT) calculations confirmed multiple interaction of the reactive substrate with CeO2, as well as preferable approximation and alignment of the nitrile group of the substrate to the active OH group on CeO2 surface. This can lead to the reduction of the entropic barrier. This is the first example of an entropy-driven substrate-specific catalysis of a nonporous metal oxide surface, which will provide a new design strategy for enzyme-inspired synthetic catalysts.
Efficient and substrate-specific hydration of nitriles to amides in water by using a CeO2 catalyst
Tamura, Masazumi,Wakasugi, Hiroko,Shimizu, Ken-Ichi,Satsuma, Atsushi
supporting information; experimental part, p. 11428 - 11431 (2011/10/18)
CeO2 acted as a reusable and effective catalyst for the hydration of various nitriles to amides in water under neutral conditions at low temperature (30-100 °C). CeO2 showed notable substrate specificity for nitriles that have a heteroatom adjacent to the α-carbon atom of the CN group (see scheme).
