4695-17-4Relevant 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.
Synthesis and antibacterial activity of 5-aryl-2- [(α-chloro-α-phenylacetyl/α- bromopropionyl)amino]-1,3,4-oxadiazoles and 2-[(5-aryl-1 ,3,4-oxadiazol-2-yl)imino]-5-phenyl/methyl-4-thiazolidinones
Ates, Oeznur,Kocabalkanlr, Ayse,Sanis, Guelten Oetuek,Ekinci, Ahmet C.,Vidin, Aylin
, p. 1134 - 1138 (2007/10/03)
Reaction of 5-aryl-2-amino-1,3,4-oxadiazoles (B(I-VI)), obtained by the oxydative cyclization of aromatic aldehyde semicarbazones (A(I-VI)), with α-chloro-α-phenylacetyl chloride and a-bromopropionyl bromide yielded 5-aryl-2-[(α-chloro-α-phenylacetyl)amino]-1,3,4-oxadiazoles (Ia-VIa) and 5-aryl-2-[(α-bromopropionyl)amino]-1, 3,4-oxadiazoles (VIIa-XIIa), respectively. Furthermore, Ia-XIIa were refluxed with ammonium thiocyanate to give 5-phenyl/methyl-2-[(5-aryl-1,3,4-oxadiazol-2-yl)imino]-4-thiazolidinones (It-XIIt). All compounds were tested for antibacterial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. They were all found to possess significant activity against S. aureus with MIC values ranging from 0.24 to 125 μg/ml. LD50 of compounds chosen as prototypes are estimated.
STUDIES ON MESOIONIC COMPOUNDS. XII. SYNTHESIS OF 1,2,3-THIADIAZOLIUM-4-AMINIDE DERIVATIVES AND THEIR CHARACTERIZATION
Masuda, Katsutada,Adachi, Jun,Morita, Hikari,Nomura, Keiichi
, p. 1743 - 1747 (2007/10/02)
New mesoionic heterocycles, 1,2,3-thiadiazolium-4-ethoxycarbonylaminides (9 and 10), were prepared by alkylation of 1,2,3-thiadiazoles (5) followed by treatment with base.Compound (9) was hydrolyzed to the hydrochloride of the corresponding 4-imine deriva
