56643-73-3Relevant academic research and scientific papers
Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
Taylor, Nicholas J.,Emer, Enrico,Preshlock, Sean,Schedler, Michael,Tredwell, Matthew,Verhoog, Stefan,Mercier, Joel,Genicot, Christophe,Gouverneur, Véronique
supporting information, p. 8267 - 8276 (2017/06/27)
Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.
PALLADIUM PINCER COMPLEX OF NORMAL AND ABNORMAL CARBENE, PREPARATION METHOD FOR THE SAME AND USES THEREOF
-
Paragraph 0034; 0035, (2016/10/08)
Palladium pincer complexes of both normal and abnormal carbene and preparation methods thereof are disclosed. Furthermore, uses of palladium pincer complexes of normal and abnormal carbene and pharmaceutical applications thereof are disclosed. Palladium pincer complex of normal and abnormal carbene are useful catalysts for C-C coupling reaction and therapeutic drugs for inhibiting tumor cell proliferation.
Synthesis and biological evaluation of novel 2-(2-arylmethylene)hydrazinyl- 4-aminoquinazoline derivatives as potent antitumor agents
Jiang, Nan,Zhai, Xin,Zhao, Yanfang,Liu, Yajing,Qi, Baohui,Tao, Haiyan,Gong, Ping
experimental part, p. 534 - 541 (2012/09/07)
Two series of novel 2-(2-arylmethylene)hydrazinyl-4-aminoquinazoline derivatives were synthesized and evaluated for their cytotoxicity against H-460, HT-29, HepG2 and SGC-7901 cancer cell lines in vitro. Most compounds displayed moderate to excellent activity, with IC50 values ranging from 0.015 to 4.09 μM against all tested cell lines, respectively. The most promising compound 9p (E)-2-(2-((1-(2,3-dichlorobenzyl)-1H-imidazol-2-yl)methylene) hydrazinyl)-N-(1-methylpiperidin-4-yl)quinazolin-4-amine with IC50 values of 0.031 μM, 0.015 μM, 0.53 μM and 0.58 μM, which was 4- to 224 times more active than references 10 and Iressa, had emerged as a lead for further structural modifications.
Synthesis, Biological Evaluation, and Molecular Modeling of 1 -Benzyl-1H-imidazoles as Selective Inhibitors of Aldosterone Synthase (CYP11B2)
Roumen, Luc,Peeters, Joris W.,Emmen, Judith M. A.,Beugels, Ilona P. E.,Custers, Erica M. G.,De Gooyer, Marcel,Plate, Ralf,Pieterse, Koen,Hilbers, Peter A. J.,Smits, Jos F. M.,Vekemans, Jef A. J.,Leysen, Dirk,Ottenheijm, Harry C. J.,Janssen, Henk M.,Rob Hermans
experimental part, p. 1712 - 1725 (2010/07/17)
Reducing aldosterone action is beneficial in various major diseases such as heart failure. Currently, this is achieved, with mineralocorticoid, receptor antagonists, however, aldosterone synthase (CYP 11B2) inhibitors may offer a promising alternative. In this study, we used three-dimensional modeling of CYP11B2 to model, the binding modes of the natural substrate 18-hydroxycorticosterone and the recently published CYP11B2 inhibitor R-fadrozole as a rational guide to design 44 structurally simple and achiral 1-benzyl-1H-imidazoles. Their syntheses, in vitro inhibitor potencies, and in silico docking are described. Some promising CYP11B2 inhibitors were identified, with our novel lead, MOERAS 115 (4-((5-phenyl-1H-imidazol-1-yl)methyl) benzonitrile) displaying an IC50 for CYP11B2 of 1.7 nM, and a CYP11B2 (versus CYP11B1) selectivity of 16.5, comparable to R-fadrozole (IC 50 for CYP11B26.0 nM, selectivity 19.8). Molecular docking of the inhibitors in the models enabled us to generate posthoc hypotheses on their binding modes, providing a valuable basis for future studies and further design of CYP11B2 inhibitors.
Synthesis and biochemical evaluation of a range of potent benzyl imidazole-based compounds as potential inhibitors of the enzyme complex 17α-hydroxylase/17,20-lyase (P45017α)
Owen, Caroline P.,Dhanani, Sachin,Patel, Chirag H.,Shahid, Imran,Ahmed, Sabbir
, p. 4011 - 4015 (2007/10/03)
The cytochrome P-450 enzyme, 17α-hydroxylase/17,20-lyase (P45017α), is a potential target in hormone-dependent cancers. Here, we report the synthesis and biochemical evaluation of a range of benzyl imidazole-based compounds which have been targeted against the two components of this enzyme, that is, 17α-hydroxylase (17α-OHase) and 17,20-lyase (lyase). The results from the biochemical testing suggest that the compounds synthesised are good inhibitors, with N-4-iodobenzyl imidazole (5) (IC50 = 10.06 μM against 17α-OHase and IC50 = 1.58 μM against lyase) showing equipotent activity against lyase compared to the standard compound, ketoconazole (KTZ) (IC50 = 3.76 ± 0.01 μM against 17α-OHase and IC50 = 1.66 ± 0.15 μM against lyase). Furthermore, the compounds tested are less potent towards the 17α-OHase component, a desirable property in the development of novel inhibitors of P45017α.
Synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of 4-substituted phenyl alkyl imidazole-based inhibitors of the enzyme complex 17α-hydroxylase/17,20-lyase (P45017α)
Patel, Chirag H.,Dhanani, Sachin,Owen, Caroline P.,Ahmed, Sabbir
, p. 4752 - 4756 (2007/10/03)
We report the preliminary results of the synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a number of phenyl alkyl imidazole-based compounds as inhibitors of the two components of 17α-hydroxylase/17,20-lyase (P45017α), that is, 17α-hydroxylase (17α-OHase) and 17,20-lyase (lyase). The results show that N-3-(4-bromophenyl) propyl imidazole (12) (IC50 = 2.95 μM against 17α-OHase and IC50 = 0.33 μM against lyase) is the most potent compound within the current study, in comparison to ketoconazole (KTZ) (IC50 = 3.76 μM against 17α-OHase and IC50 = 1.66 μM against lyase). Modelling of these compounds suggests that the length of the alkyl chain enhances the interaction between the inhibitor and the area of the active site corresponding to the C(3) area of the steroid backbone, thereby increasing potency.
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.
