147269-01-0Relevant articles and documents
Base-catalysed 18F-labelling of trifluoromethyl ketones. Application to the synthesis of 18F-labelled neutrophil elastase inhibitors
Meyer, Denise N.,Cortés González, Miguel A.,Jiang, Xingguo,Johansson-Holm, Linus,Pourghasemi Lati, Monireh,Elgland, Mathias,Nordeman, Patrik,Antoni, Gunnar,Szabó, Kálmán J.
supporting information, p. 8476 - 8479 (2021/09/02)
A new method for the fluorine-18 labelling of trifluoromethyl ketones has been developed. This method is based on the conversion of a-COCF3 functional group to a difluoro enol silyl ether followed by halogenation and fluorine-18 labelling. The utility of this new method was demonstrated by the synthesis of fluorine-18 labelled neutrophil elastase inhibitors, which are potentially useful for detection of inflammatory disorders.
Pyridone-based peptidomimetic inhibitors of interleukin-1β-converting enzyme (ICE)
Semple, Graeme,Ashworth, Doreen M.,Baker, Graham R.,Batt, Andrzej R.,Baxter, Andrew J.,Benzies, David W.M.,Elliot, Lucy H.,Evans, D. Michael,Franklin, Richard J.,Hudson, Peter,Jenkins, Paul D.,Pitt, Gary R.,Rooker, David P.,Sheppard, Andrew,Szelke, Michael,Yamamoto, Satoshi,Isomura, Yasuo
, p. 1337 - 1342 (2007/10/03)
New potent, reversible inhibitors of recombinant human Interleukin-1 β-converting enzyme (ICE, caspase-1) with significantly reduced peptide character are described. The compounds were designed by incorporation of pyridone and pyrimidone heterocyclic replacements for the P2-P3 amino acids of the native substrate and were optimised by manipulation of peripheral alkyl and aryl substituents.
Nonpeptidic inhibitors of human leukocyte elastase. 2. Design, synthesis, and in vitro activity of a series of 3-amino-6-arylopyridin-2-one trifluoromethyl ketones
Damewood Jr.,Edwards,Feeney,Gomes,Steelman,Tuthill,Williams,Warner,Woolson,Wolanin,Veale
, p. 3303 - 3312 (2007/10/02)
A series of potent nonpeptidic inhibitors of the enzyme human leukocyte elastase (HLE) is reported. These inhibitors contain a 3-amino-2-pyridone ring as a central template in which the pyridone carbonyl and 3-position NH group are thought to form important hydrogen bonding interactions with the Val-216 residue of HLE. Substitution of the 6-position of the pyridone ring by various alkyl and aryl groups was found to afford increases in the in vitro potency of these inhibitors. A 6-position phenyl group, compound 10f, was found to result in a large increase in binding affinity, which was not obtained when the phenyl group was placed in either the 4- or 5-position of the molecule. Compound 10f was found to have good selectivity for HLE over other proteolytic enzymes, with the exception of bovine pancreatic chymotrypsin (BPC). Substitution of the 6-phenyl group in these molecules was found to decrease binding affinity for BPC without adversely affecting affinity for HLE.
