147269-03-2Relevant 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.
, 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.
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.
Nonpeptidic Inhibitors of Human Leukocyte Elastase. 3. Design, Synthesis, X-ray Crystallographic Analysis, and Structure-Activity Relationships for a Series of Orally Active 3-Amino-6-phenylpyridin-2-one Trifluoromethyl Ketones
Bernstein, Peter R.,Andisik, Don,Bradley, Prudence K.,Bryant, Craig B.,Ceccarelli, Christopher,et al.
, p. 3313 - 3326 (2007/10/02)
A series of nonpeptidic inhibitors of human leukocyte elastase (HLE) is reported.These trifluoromethyl ketone-based inhibitors contain a 3-amino-6-phenylpyridone group as a central template.The effect of varying the N-3 substituent in these inhibitors on
