2302-39-8Relevant academic research and scientific papers
Tuning the electronic properties of tetradentate iron-NHC complexes: Towards stable and selective epoxidation catalysts
B?th, Alexander D.,Bernd, Marco A.,Dyckhoff, Florian,Hofmann, Benjamin J.,Kühn, Fritz E.,Oberkofler, Jens,Reich, Robert M.,Schlagintweit, Jonas F.
, p. 548 - 561 (2020)
Two sets of bio-inspired non-heme iron complexes, each comprising of an FeII and FeIII species, bearing 16-membered macrocyclic tetradentate N-heterocyclic carbene ligands are reported. The complexes exhibit trans labile coordination sites, are characterized by means of NMR, ESI-MS, elemental analysis, SC-XRD and cyclic voltammetry and assessed as olefin epoxidation (pre-)catalysts applying H2O2 as oxidant. Sc(OTf)3 and AcOH are evaluated as Lewis and Br?nsted acidic additives, respectively, resulting in partially noticeable improvement in catalytic performance. Hereby, complex 2b shows high stability (TON = 1000 at 20 °C), high temperature tolerance and advances in the more challenging epoxidation of terminal and functionalized olefins. Furthermore, in-depth DFT calculations are conducted to put the catalysts’ structural and electronic features into relation with the catalytic results.
Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis
Li, Li,Lelyveld, Victor S.,Prywes, Noam,Szostak, Jack W.
, p. 3986 - 3989 (2016)
Phosphoroimidazolides play a critical role in several enzymatic phosphoryl transfer reactions and have been studied extensively as activated monomers for nonenzymatic nucleic acid replication, but the detailed mechanisms of these phosphoryl transfer reactions remain elusive. Some aspects of the mechanism can be deduced by studying the hydrolysis reaction, a simpler system that is amenable to a thorough mechanistic treatment. Here we characterize the transition state of phosphoroimidazolide hydrolysis by kinetic isotope effect (KIE) and linear free energy relationship (LFER) measurements, and theoretical calculations. The KIE and LFER observations are best explained by calculated loose transition structures with extensive scissile bond cleavage. These three-dimensional models of the transition state provide the basis for future mechanistic investigations of phosphoroimidazolide reactions.
Rational Design, Synthesis and Evaluation of Novel C6-Bicycloalkaneimidazole Containing Imidazo[1,2-b]pyridazines for ASK1 Inhibition
Lee, Yujin,Jang, Jiyoon,Bibi, Maimoona,Duggirala, Krishna Babu,Ji, Sang Hee,Lee, Ji Hun,Ahn, Sunjoo,Song, Jin Sook,Chae, Chong Hak,Kim, Seong Hwan,Lee, Kwangho
, p. 872 - 877 (2021/05/10)
Apoptosis signal-regulating kinase 1 (ASK1) is a member of mitogen-activated protein kinase kinase kinase (MAP3K) family that involves downstream phosphorylation of MAP kinases, c-Jun N-terminal kinases, and p38 MAP kinases. ASK1 inhibitors could possibly be beneficial for ameliorating the development and progression of diseases. Especially, ASK1 has been of interest as one of therapeutic targets for nonalcoholic fatty liver disease as the most common chronic liver diseases including simple steatosis and nonalcoholic steatohepatitis. In this manuscript, novel ASK1 inhibitor lead KTA-29 which has an imidazo[1,2-b]pyridazine core with novel C6-bicycloheptaneimidazole is disclosed. With the novel imidazo[1,2-b]pyridazine core, structure-activity-relationship study for ASK1 potency is described and KTA-29 affinity toward ASK1 with molecular modeling study is explained.
Design, synthesis, structure-activity relationships study and X-ray crystallography of 3-substituted-indolin-2-one-5-carboxamide derivatives as PAK4 inhibitors
Guo, Jing,Zhao, Fan,Yin, Wenbo,Zhu, Mingyue,Hao, Chenzhou,Pang, Yu,Wu, Tianxiao,Wang, Jian,Zhao, Dongmei,Li, Haitao,Cheng, Maosheng
, p. 197 - 209 (2018/06/12)
We have previously described the identification of indolin-2-one-5-carboxamides as potent PAK4 inhibitors. This study expands the structure-activity relationships on our original series by presenting several modifications in the lead compounds, 2 and 3. A series of novel derivatives was designed, synthesized, and evaluated in biochemical and cellular assay. Most of this series displayed nanomolar biochemical activity and potent antiproliferative activity against A549 and HCT116 cells. The representative compound 10a exhibited excellent enzyme inhibition (PAK4 IC50 = 25 nM) and cellular potency (A549 IC50 = 0.58 μM, HCT116 IC50 = 0.095 μM). An X-ray structure of compound 10a bound to PAK4 was obtained. Crystallographic analysis confirmed predictions from molecular modeling and helped refine SAR results. In addition, Compound 10a displayed focused multi-targeted kinase inhibition, good calculated drug-likeness properties. Further profiling of compound 10a revealed it showed weak inhibitory activity against various isoforms of human cytochrome P450.
Syntheses of polyalkylated imidazoles
Evjen, Sigvart,Fiksdahl, Anne
supporting information, p. 1392 - 1399 (2017/07/25)
We have developed improved general simple methods for large-scale preparation of polyalkylated imidazoles by improved multicomponent synthesis from commercially available starting materials. A large range of NH- and N-alkyl-polyalkylimidazoles (40 in total, including novel compounds) has been synthesized.
Halogen bond anion templated assembly of an imidazolium pseudorotaxane
Serpell, Christopher J.,Kilah, Nathan L.,Costa, Paulo J.,Felix, Vitor,Beer, Paul D.
supporting information; experimental part, p. 5322 - 5326 (2010/10/19)
Halogen bonding has been exploited in the assembly of an interpenetrated molecular system. The strength of chloride-anion-templated pseudorotaxane formation with a 2-bromo-functionalized imidazolium threading component and an isophthalamide macrocycle (see picture) is significantly enhanced compared to hydrogen-bonded pseudorotaxane analogues. (Figure Presented).
Synthesis of 4,5-substituted imidazoles by a fast condensation of 1,2-diketones and urotropine in heterogeneous medium
Bratulescu, George
experimental part, p. 2319 - 2320 (2010/02/28)
Starting from 1,2-diketones and urotropine in the presence of ammonium acetate, a simple and efficient solventless microwave-assisted synthesis of 4,5-disubstituted imidazoles was accomplished. Georg Thieme Verlag Stuttgart.
Kinetics and mechanism of the nucleophilic cleavage of disulfide bond in 2,2′-dithio-diimidazoles with hydroxide ions
Kurzawa,Suszka
, p. 1487 - 1494 (2008/09/18)
Kinetics of the cleavage of disulfide bond of dithiobisdisulfides of diimidazoles to their parent imidazoles by hydroxide ion have been investigated spectrophotometrically. Rate equation and other observations suggest that the nucleophilic attack of hydroxide ion on one of the sulfur atoms of disulfide bond is a rate limiting step. This process is accompanied by much slower, parallel reaction with water as a nucleophile. Hence the full kinetic equation for nucleophilic cleavage of 2,2′-dithio-diimidazoles in aqueous alkaline solutions is a two-term equation: -(d[RSSR]/dt) = k1 [RSSR][OHl + k2[RSSR][H2O], where k1 > k2. The mechanism of the reaction is proposed.
Synthesis, acidity and 19F NMR characteristics of imidazoles bearing 1-fluorinated substituents with potential application as probes for intracellular pH determination.
Harper, Jacquie L.,Smith, Robin A. J.,Bedford, Jennifer J.,Leader, John P.
, p. 8211 - 8224 (2007/10/03)
A series of 1-substituted imidazoles containing fluorine have been prepared. These compounds were identified as potentially useful probes for intracellular pH determination based on 19F NMR. Key parameters including pK(a), 19F NMR chemical shift sensitivity, water solubility and low toxicity were identified and included in the target molecule selection process. The pK(a) and 19F NMR parameters of the molecules are reported and trends analysed.
A NEW SYNTHESIS OF UNSUBSTITUTED, 4(5), AND 4,5-SUBSTITUTED 1H-IMIDAZOLES.
Khalaj, A.,Ghafari, M.
, p. 5019 - 5020 (2007/10/02)
Novel synthesis of the title compounds based on the reaction of N-(aminomethyl) benzamide with 1,2-dicarbonyl compounds is described.
