1621-91-6Relevant articles and documents
Mass Spectrometry of Nitroazoles. 3-Ortho Effects: The loss of OH. and H2O from Methyl Substituted Nitrodiazoles
Luijten, W. C. M. M.,Thuijl, J. van
, p. 299 - 303 (1982)
Methyl substituted nitrodiazoles which have the substituents at adjacent positions in the ring are subject to several ortho effects.Deuterium labelling of the methyl group and the mobile N-bonded hydrogen show that the loss of OH. originates from the substituents.In some cases the N-bonded hydrogen atom participates also in the loss of OH. and of H2O.
Synthesis and evaluation of original bioisosteres of bacterial type IIA topoisomerases inhibitors
Petrella, Stéphanie,Aubry, Alexandra,Janvier, Geneviève,Coutant, Eloi P.,Cartier, Alex,Dao, Thuy-Ha,Bonhomme, Frédéric J.,Motreff, Laurence,Pissis, Cédric,Bizet, Chantal,Clermont, Dominique,Begaud, Evelyne,Retailleau, Pascal,Munier-Lehmann, Hélène,Capton, Estelle,Mayer, Claudine,Janin, Yves L.
, p. 240 - 250 (2015)
A recently discovered series of inhibitors of the ATPase function of bacterial type IIA topoisomerases featuring a carboxypyrrole component led us to attempt to replace this group with a potentially bioisosteric carboxypyrazole. Accordingly, synthetic pathways to 2-(4-(1H-pyrazole-5-carboxamido)piperidin-1-yl)thiazole-5-carboxylic acids or 2-(4-(N-methyl-1H-pyrazole-5-carboxamido)piperidin-1-yl)thiazole-5-carboxylic acids featuring an array of substituents on the pyrazole ring were explored. Unfortunately, none of the analogues made were effective on the ATPase function of Mycobacterium tuberculosis gyrase as well on the DNA supercoiling activity of the whole gyrase of M. tuberculosis and Escherichia coli. However, this work is still providing original insights in chemistry as well as in the structure-activity relationships of this series of inhibitors.
Oxidation of imidazole- and pyrazole-derived aldehydes by plant aldehyde dehydrogenases from the family 2 and 10
Fr?mmel, Jan,Kon?itíková, Radka,Kope?ny, David,Soural, Miroslav,?ebela, Marek
, p. 194 - 201 (2019/03/06)
Plant cytosolic aldehyde dehydrogenases from family 2 (ALDH2s, EC 1.2.1.3) are non-specific enzymes and participate for example in the metabolism of acetaldehyde or biosynthesis of phenylpropanoids. Plant aminoaldehyde dehydrogenases (AMADHs, ALDH10 family, EC 1.2.1.19) are broadly specific and play an important role in polyamine degradation or production of osmoprotectants. We have tested imidazole and pyrazole carbaldehydes and their alkyl-, allyl-, benzyl-, phenyl-, pyrimidinyl- or thienyl-derivatives as possible substrates of plant ALDH2 and ALDH10 enzymes. Imidazole represents a building block of histidine, histamine as well as certain alkaloids. It also appears in synthetic pharmaceuticals such as imidazole antifungals. Biological compounds containing pyrazole are rare (e.g. pyrazole-1-alanine and pyrazofurin antibiotics) but the ring is often found as a constituent of many synthetic drugs and pesticides. The aim was to evaluate whether aldehyde compounds based on azole heterocycles are oxidized by the enzymes, which would further support their expected role as detoxifying aldehyde scavengers. The analyzed imidazole and pyrazole carbaldehydes were only slowly converted by ALDH10s but well oxidized by cytosolic maize ALDH2 isoforms (particularly by ALDH2C1). In the latter case, the respective Km values were in the range of 10–2000 μmol l?1; the kcat values appeared mostly between 0.1 and 1.0 s?1. The carbaldehyde group at the position 4 of imidazole was oxidized faster than that at the position 2. Such a difference was not observed for pyrazole carbaldehydes. Aldehydes with an aromatic substituent on their heterocyclic ring were oxidized faster than those with an aliphatic substituent. The most efficient of the tested substrates were comparable to benzaldehyde and p-anisaldehyde known as the best aromatic aldehyde substrates of plant cytosolic ALDH2s in vitro.
Optimization and biological evaluation of 2-aminobenzothiazole derivatives as Aurora B kinase inhibitors
Lee, Eun,An, Ying,Kwon, Junhee,Kim, Keun Il,Jeon, Raok
, p. 3614 - 3622 (2017/06/13)
A strong relationship between abnormal functions of Aurora kinases and tumorigenesis has been reported for decades. Consequently, Aurora kinases serve as potential targets for anticancer agents. Here, we identified aminobenzothiazole derivatives as novel inhibitors of Aurora B kinase through bioisosteric replacement of the previous inhibitors, aminobenzoxazole derivatives. Most of the urea-linked aminobenzothiazole derivatives showed potent and selective inhibitory activity against Aurora B kinase over Aurora A kinase. Molecular modeling indicated that compound 15g bound well to the active site of Aurora B kinase and formed the essential hydrogen bonds. The potent compounds, 15g and 15k, were selected, and their biological effects were evaluated using HeLa cell lines. It was found that these compounds inhibited the phosphorylation of histone H3 at Ser10 and induced G2/M cell cycle arrest. We suggest that the reported compounds have the potential to be further developed as anticancer therapeutics.
