5841-63-4Relevant articles and documents
Identification of a New Zinc Binding Chemotype by Fragment Screening
Chrysanthopoulos, Panagiotis K.,Mujumdar, Prashant,Woods, Lucy A.,Dolezal, Olan,Ren, Bin,Peat, Thomas S.,Poulsen, Sally-Ann
, p. 7333 - 7349 (2017/09/22)
The discovery of a new zinc binding chemotype from screening a nonbiased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted 2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the zinc metalloenzyme carbonic anhydrase II (CA II). This affinity approached that of fragment sized primary benzenesulfonamides, the classical zinc binding group found in most CA II inhibitors. Protein X-ray crystallography established that 3-unsubstituted 2,4-oxazolidinediones bound to CA II via an interaction of the acidic ring nitrogen with the CA II active site zinc, as well as two hydrogen bonds between the oxazolidinedione ring oxygen and the CA II protein backbone. Furthermore, 3-unsubstituted 2,4-oxazolidinediones appear to be a viable starting point for the development of an alternative class of CA inhibitor, wherein the medicinal chemistry pedigree of primary sulfonamides has dominated for several decades.
N-Acyl and N-sulfonyloxazolidine-2,4-diones are pseudo-irreversible inhibitors of serine proteases
Santana, Ana Bela,Lucas, Susana D.,Goncalves, Lidia M.,Correia, Henrique F.,Cardote, Teresa A.F.,Guedes, Rita C.,Iley, Jim,Moreira, Rui
supporting information; experimental part, p. 3993 - 3997 (2012/07/03)
The synthesis, inhibitory activity and mode of action of oxazolidine-2,4-diones against porcine pancreatic elastase, here used as a model for human neutrophil elastase, are reported. The nature of N-substitution at the oxazolidine-2,4-dione scaffold has large effect on the inhibitory potency against elastase. N-Acyl and N-sulfonyloxazolidine-2,4-diones emerged as potent pseudo-irreversible inhibitors, displaying high second-order rate constants for PPE inactivation. The title compounds were also shown to be potent inhibitors of human neutrophil elastase (HNE) and proteinase-3, and weak inhibitors of human cathepsin G. The results herein presented show that the oxazolidine-2,4-diones represent a new promising class of serine protease inhibitors.
Structure elucidation of 2-amino-5-phenyl-2-oxazolin-4-one (pemoline) and X-ray structure of its hydrolysis product 5-phenyl-oxazolidine-2,4-dione
Ku?, Piotr,Jones, Peter G.,Celiński, Rafa?
, p. 853 - 857 (2007/10/03)
In this study we compare spectroscopic properties of pemoline (2-amino-5-phenyl-2-oxazolin-4-one) and its acid hydrolysis product 5-phenyl-oxazolidine-2,4-dione. Crystallization of pemoline from aqueous acetic acid gave single crystals of compound 2, the structure of which was determined by X-ray studies. All four crystallographically independent molecules form dimers linked by N-H?O=C hydrogen bonds.
