The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
Wei Huang - One of the best experts on this subject based on the ideXlab platform.
-
extremely high ph stability for a class of heterocyclic azo dyes having the common n2 n6 bis 3 methoxypropyl pyridine 2 6 diamine coupling component
Dyes and Pigments, 2017Co-Authors: Xiaolei Zhao, Teng Jun, Yanan Feng, Huifen Qian, Wei HuangAbstract:Abstract A series of N 2 , N 6 -bis(3-methoxypropyl)pyridine-2,6-diamine azo dyes, prepared by coupling 2,6-bis((3-methoxypropyl)amino)-4-methylnicotinonitrile and diazotized substituted anilines with distinguishable electron push-pull abilities, have been described in this paper. The new dyes undergoing double functional group transformation (FGT) show extremely high pH stability compared to corresponding mono FGT dyes, which could be ascribed to the introduction of the second 3-methoxypropylamino group forming the new pyridine-2,6-diamine backbone. It is noted that the unusual transformation from D− π −A to A− π −D system has been verified for our multi-substituted phenyl-azo-pyridine FGT products. The adjustment of electron-donating and electron-withdrawing phenyl and pyridine substituted groups narrows the discrepancy of electron push-pull capabilities for dizao and coupling components, which makes possible the transformation for roles of donor and acceptor. It is believed that the achievement of extremely high pH stability for pyridine-2,6-diamine based heterocyclic azo dyes is regarded as a useful exploration for designing new FGT modified pyridone dyes.
-
spectral and structural comparisons on four pairs of isomeric 4 and 2 aminobenzoic acid based aromatic heterocyclic dyes
Journal of Chemical Crystallography, 2017Co-Authors: Yuanyuan Wang, Yanan Feng, Huifen Qian, Yuehua Wang, Wei HuangAbstract:Four pairs of isomeric aromatic heterocyclic dyes 1 – 8, synthesized from the diazotization and subsequent coupling reactions between 4 or 2-aminobenzoic acid as the diazo component and different N-substituted pyridone precursors as the coupling component, have been characterized and compared including UV–Vis and 1H NMR spectra, X-ray single-crystal structures and related DFT computations. It is noted that X-ray single-crystal diffraction analyses reveal that all of them adopt the same hydrazone-tautomeric form and planar molecular conformation between the pyridine and phenyl rings. However, different intramolecular and intermolecular hydrogen bonding interactions are observed because of the introduction of an electron-withdrawing carboxylic acid group at the ortho or para position in the phenyl ring. 4-Aminobenzoic acid and 2-aminobenzoic acid have been used as the diazo components to couple with different N-substituted pyridone precursors to produce four pairs of isomeric aromatic heterocyclic dyes, for which 1H NMR spectral, UV–Vis spectral and single-crystal structural comparisons have been made.
-
structural and computational studies of azo dyes in the hydrazone form having the same pyridine 2 6 dione component ii c i disperse yellow 119 and c i disperse yellow 211
Dyes and Pigments, 2008Co-Authors: Wei HuangAbstract:Abstract The molecular and crystal structures of two yellow, azo disperse dyes having the same pyridine-1-ethyl-3-cyano-4-methyl-2,6-dione backbone, namely C.I. Disperse Yellow 119 and C.I. Disperse Yellow 211 were studied. Both dyes crystallize in the hydrazone form both at 291 and 120 K, with hydrogen bonding and π–π stacking interactions playing important roles in determining the packing frameworks; mean interlayer separations of 3.002(3) and 3.316(6) A, respectively, were obtained. Theoretical calculations were undertaken to compare the energy differences between the single-crystal and the energy-minimized structures of the compounds as well as those between the pyridine-2,6-dione and the 2-hydroxy-6-pyridone isomers.
Yaquan Zhang - One of the best experts on this subject based on the ideXlab platform.
-
Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities.
Journal of medicinal chemistry, 2008Co-Authors: Kyoung S. Kim, Cai Zhen-wei, Donna D. Wei, Robert J. Schmidt, David K. Williams, Liping Zhang, Louis J. Lombardo, George L. Trainor, Dianlin Xie, Yaquan ZhangAbstract:Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC50 value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-Pyridone and pyridine N-oxide inhibitors such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent antiproliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC50 values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTL-16 human gastric carcinoma xenograft model.
Fredrik Almqvist - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of substituted 4-Pyridones and 4-aminopyridinium salts via a one-pot pyridine synthesis
Tetrahedron Letters, 2010Co-Authors: Hans Andersson, Sajal Das, Magnus Gustafsson, Roger Olsson, Fredrik AlmqvistAbstract:Synthesis of substituted 4-benzyloxypyridinium salts by the addition of Grignard reagents to pyridine N-oxides provides an efficient route for obtaining substituted 4-Pyridones or 4-aminopyridinium salts.
-
Functionalization of bicyclic 2-pyridones targeting pilus biogenesis in uropathogenic Escherichia coli
Tetrahedron Letters, 2007Co-Authors: Nils Pemberton, Scott J. Hultgren, Jerome S. Pinkner, Jennifer M. Jones, Lotta Jakobsson, Fredrik AlmqvistAbstract:Substituted bicyclic 2-pyridones, termed pilicides, prevent pilus assembly in uropathogenic Escherichia coli. Based on the bioactive methyl ester protected 2-pyridone 4, further functionalization at C-6 has yielded a set of new compounds, which have been evaluated for their ability to inhibit pilus formation in uropathogenic E. coli. The key intermediate in the synthesis was formylated 2-pyridone 5, which could be obtained via a Vilsmeier reaction. This versatile intermediate was converted into secondary and tertiary amines via reductive amination and could also be converted to other interesting functionalities using simple chemical transformations.
Ujjini H. Manjunatha - One of the best experts on this subject based on the ideXlab platform.
-
Structure activity relationships of 4-hydroxy-2-pyridones: A novel class of antituberculosis agents
European journal of medicinal chemistry, 2015Co-Authors: Ujjini H. Manjunatha, Srinivasa P. S. Rao, Christian G. Noble, Luis R. Camacho, Ngai Ling, Maxime Hervé, Anne Goh, Stefan Peukert, Thierry T. DiaganaAbstract:Pyridone 1 was identified from a high-throughput cell-based phenotypic screen against Mycobacterium tuberculosis (Mtb) including multi-drug resistant tuberculosis (MDR-TB) as a novel anti-TB agent and subsequently optimized series using cell-based Mtb assay. Preliminary structure activity relationship on the isobutyl group with higher cycloalkyl groups at 6-position of pyridone ring has enabled us to significant improvement of potency against Mtb. The lead compound 30j, a dimethylcyclohexyl group on the 6-position of the pyridone, displayed desirable in vitro potency against both drug sensitive and multi-drug resistant TB clinical isolates. In addition, 30j displayed favorable oral pharmacokinetic properties and demonstrated in vivo efficacy in mouse model. These results emphasize the importance of 4-hydroxy-2-pyridones as a new chemotype and further optimization of properties to treat MDR-TB.
-
Direct inhibitors of InhA are active against Mycobacterium tuberculosis
Science Translational Medicine, 2015Co-Authors: Ujjini H. Manjunatha, Srinivasa P. S. Rao, Ravinder Reddy Kondreddi, Christian G. Noble, Luis R. Camacho, Bee Huat Tan, Ng L., Suresh B. LakshminarayanaAbstract:New chemotherapeutic agents are urgently required to combat the global spread of multidrug-resistant tuberculosis (MDR-TB). The mycobacterial enoyl reductase InhA is one of the few clinically validated targets in tuberculosis drug discovery. We report the identification of a new class of direct InhA inhibitors, the 4-hydroxy-2-pyridones, using phenotypic high-throughput whole-cell screening. This class of orally active compounds showed potent bactericidal activity against common isoniazid-resistant TB clinical isolates. Biophysical studies revealed that 4-hydroxy-2-pyridones bound specifically to InhA in an NADH (reduced form of nicotinamide adenine dinucleotide)–dependent manner and blocked the enoyl substrate–binding pocket. The lead compound NITD-916 directly blocked InhA in a dose-dependent manner and showed in vivo efficacy in acute and established mouse models of Mycobacterium tuberculosis infection. Collectively, our structural and biochemical data open up new avenues for rational structure-guided optimization of the 4-hydroxy-2-pyridone class of compounds for the treatment of MDR-TB.
Kyoung S. Kim - One of the best experts on this subject based on the ideXlab platform.
-
Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities.
Journal of medicinal chemistry, 2008Co-Authors: Kyoung S. Kim, Cai Zhen-wei, Donna D. Wei, Robert J. Schmidt, David K. Williams, Liping Zhang, Louis J. Lombardo, George L. Trainor, Dianlin Xie, Yaquan ZhangAbstract:Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC50 value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-Pyridone and pyridine N-oxide inhibitors such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent antiproliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC50 values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTL-16 human gastric carcinoma xenograft model.
