29262-57-5Relevant academic research and scientific papers
Analogues of the Herbicide, N-Hydroxy- N-isopropyloxamate, Inhibit Mycobacterium tuberculosis Ketol-Acid Reductoisomerase and Their Prodrugs Are Promising Anti-TB Drug Leads
Kandale, Ajit,Patel, Khushboo,Hussein, Waleed M.,Wun, Shun Jie,Zheng, Shan,Tan, Lendl,West, Nicholas P.,Schenk, Gerhard,Guddat, Luke W.,McGeary, Ross P.
, p. 1670 - 1684 (2021/02/27)
New drugs to treat tuberculosis (TB) are urgently needed to combat the increase in resistance observed among the current first-line and second-line treatments. Here, we propose ketol-acid reductoisomerase (KARI) as a target for anti-TB drug discovery. Twenty-two analogues of IpOHA, an inhibitor of plant KARI, were evaluated as antimycobacterial agents. The strongest inhibitor of Mycobacterium tuberculosis (Mt) KARI has a Ki value of 19.7 nM, fivefold more potent than IpOHA (Ki = 97.7 nM). This and four other potent analogues are slow- and tight-binding inhibitors of MtKARI. Three compounds were cocrystallized with Staphylococcus aureus KARI and yielded crystals that diffracted to 1.6-2.0 ? resolution. Prodrugs of these compounds possess antimycobacterial activity against H37Rv, a virulent strain of human TB, with the most active compound having an MIC90 of 2.32 ± 0.04 μM. This compound demonstrates a very favorable selectivity window and represents a highly promising lead as an anti-TB agent.
Synthesis, crystal structure, and insecticidal activity of novel N-alkyloxyoxalyl derivatives of 2-arylpyrrole
Zhao, Yu,Mao, Chunhui,Li, Yongqiang,Zhang, Pengxiang,Huang, Zhiqiang,Bi, Fuchun,Huang, Runqiu,Wang, Qingmin
experimental part, p. 7326 - 7332 (2010/06/11)
Two series of novel N-alkyloxyoxalyl derivatives of 2-arylpyrrole were synthesized, and their structures were characterized by 1H NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities, and their insecticidal activities against oriental armyworm, mosquito, and spider mite are comparable to those of the commercialized Chlorfenapyr.
Inhibitors of hepatitis C virus NS3·4A protease. Effect of P4 capping groups on inhibitory potency and pharmacokinetics
Perni, Robert B.,Chandorkar, Gurudatt,Cottrell, Kevin M.,Gates, Cynthia A.,Lin, Chao,Lin, Kai,Luong, Yu-Ping,Maxwell, John P.,Murcko, Mark A.,Pitlik, Janos,Rao, Govinda,Schairer, Wayne C.,Drie, John Van,Wei, Yunyi
, p. 3406 - 3411 (2008/02/08)
Reversible tetrapeptide-based compounds have been shown to effectively inhibit the hepatitis C virus NS3·4A protease. Inhibition of viral replicon RNA production in Huh-7 cells has also been demonstrated. We show herein that the inclusion of hydrogen bond donors on the P4 capping group of tetrapeptide-based inhibitors result in increased binding potency to the NS3·4A protease. The capping groups also impart significant effects on the pharmacokinetic profile of these inhibitors.
Hydrogen bond patterns in solid state carboxylic acids. Vibrational behaviour of the catamer pattern as exhibited by the N-alkyloxamic acids
Wolfs, Ilse,Desseyn, Herman O.
, p. 1521 - 1528 (2007/10/03)
The vibrational study presented in this publication shows that the N-alkyloxamic acids are hydrogen bonded through a catamer hydrogen bond pattern in the solid state. Two different hydrogen bond patterns are possible for these products, and these patterns can be very clearly distinguished by their vibrational behaviour. Deuteration and low temperature spectra make the assignment and characterisation more obvious.
Reactivity of Carbamoyl Radicals. A New, General, Convenient Free-Radical Synthesis of Isocyanates from Monoamides of Oxalic Acid
Minisci, Francesco,Fontana, Francesca,Coppa, Fausta,Yan, Yong Ming
, p. 5430 - 5433 (2007/10/02)
A new, general, simple synthesis of isocyanates was developed by oxidation of monoamides of oxalix acid with peroxydisulfate catalyzed by Ag and Cu salts.The reaction was carried out in a two-phase system (water and an organic solvent), and it is suitable also for practical applications, due to the simple experimental conditions and the inexpensive as well as nontoxic reagents.The first example of homolytic intramolecular aromatic carbamoylation is also reported.
Inhibitors of Thermus thermophilus isopropylmalate dehydrogenase
Pirrung,Han,Ludwig
, p. 2430 - 2436 (2007/10/02)
In an attempt to use mechanism-based design for the discovery of inhibitors of the isopropylmalate dehydrogenase from T. thermophilus, we have prepared and studied a number of potential mimics for an intermediate in the oxidative decarboxylation of isopropyl malate, the enol or enolate of α-ketoisocaproate. Because hydroxamate and dicarboxylate enolate mimics are strong, uncompetitive inhibitors of the enzyme and vinyl fluoride enol mimics are weak, competitive inhibitors, it is suggested that the reaction involves the enolate. The uncompetitive inhibition by a number of anionic compounds suggests, in combination with previous studies in other laboratories, that they mimic the enolate product of the decarboxylation. An explanation for the potency of the inhibition of IMDH by these compounds is proposed based on the electrostatic interaction of product and cofactor.
