5470-22-4Relevant academic research and scientific papers
Discovery of potent c-MET inhibitors with new scaffold having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine headgroups
Jiang, Yingnan,Zhang, Ke,Gao, Suyu,Wang, Guihua,Huang, Jian,Wang, Jinhui,Chen, Lixia
, (2016/07/06)
Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N1-(3-fluoro-4-methoxyphenyl)-N3-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c-MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy.
Electrophilicity and nucleophilicity of commonly used aldehydes
Pratihar, Sanjay
, p. 5781 - 5788 (2014/07/22)
The present approach for determining the electrophilicity (E) and nucleophilicity (N) of aldehydes includes a kinetic study of KMNO4 oxidation and NaBH4 reduction of aldehydes. A transition state analysis of the KMNO4 promoted aldehyde oxidation reaction has been performed, which shows a very good correlation with experimental results. The validity of the experimental method has been tested using the experimental activation parameters of the two reactions. The utility of the present approach is further demonstrated by the theoretical versus experimental relationship, which provides easy access to E and N values for various aldehydes and offers an at-a-glance assessment of the chemical reactivity of aldehydes in various reactions. the Partner Organisations 2014.
Design and synthesis of novel 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4- triazol-3-yl)pyridines as potential antitumor agents
Qin, Mingze,Zhai, Xin,Xie, Hongbo,Ma, Junjie,Lu, Kuan,Wang, Yu,Wang, Lihui,Gu, Yucheng,Gong, Ping
, p. 47 - 58 (2014/06/09)
New 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4-triazol-3-yl)pyridine derivatives were synthesized and evaluated for their in vitro cytotoxicity against five cancer cell lines namely MKN-45, H460, HT-29, A549 and U87MG, as well as the normal cell line WI-38. Nearly all the compounds exhibited superior potency to sorafenib with a better selectivity towards the MKN-45, H460 and HT-29 cell lines. In addition, the enzymatic screening result demonstrated that the optimized compounds possessed potent Raf kinase inhibition as well as favorable enzyme selectivity. The most promising compound, 11f, showed high levels of cytotoxicity against MKN-45, H460 and HT-29 cells with IC50 values of 51, 72 and 130 nM, respectively, which are 45.5, 30.4 and 27.8 folds higher than the corresponding IC50 values for sorafenib against these cell lines. Structure-activity relationships revealed that the dimethylaminoethyl group was crucial for high activity.
Dual-action inhibitors of HIF prolyl hydroxylases that induce binding of a second iron ion
Yeoh, Kar Kheng,Chan, Mun Chiang,Thalhammer, Armin,Demetriades, Marina,Chowdhury, Rasheduzzaman,Tian, Ya-Min,Stolze, Ineke,McNeill, Luke A.,Lee, Myung Kyu,Woon, Esther C. Y.,MacKeen, Mukram M.,Kawamura, Akane,Ratcliffe, Peter J.,Mecinovi?, Jasmin,Schofield, Christopher J.
supporting information, p. 732 - 745 (2013/02/26)
Inhibition of the hypoxia-inducible factor (HIF) prolyl hydroxylases (PHD or EGLN enzymes) is of interest for the treatment of anemia and ischemia-related diseases. Most PHD inhibitors work by binding to the single ferrous ion and competing with 2-oxoglutarate (2OG) co-substrate for binding at the PHD active site. Non-specific iron chelators also inhibit the PHDs, both in vitro and in cells. We report the identification of dual action PHD inhibitors, which bind to the active site iron and also induce the binding of a second iron ion at the active site. Following analysis of small-molecule iron complexes and application of non-denaturing protein mass spectrometry to assess PHD2·iron· inhibitor stoichiometry, selected diacylhydrazines were identified as PHD2 inhibitors that induce the binding of a second iron ion. Some compounds were shown to inhibit the HIF hydroxylases in human hepatoma and renal carcinoma cell lines. The Royal Society of Chemistry 2013.
ALLOSTERIC MODULATORS OF 5-HYDROXYTRYPTAMINE 2C RECEPTOR (5-HT2CR)
-
Paragraph 00091, (2013/06/27)
[000166] Embodiments of the invention are directed to methods of identifying, methods of synthesizing, and compositions identified as allosteric modulators of 5-HT2cR.
Synthesis and biological evaluation of novel 4-(2-fluorophenoxy)-2-(1h- tetrazol-1-yl)pyridines bearing semicarbazone moieties as potent antitumor agents
Qin, Mingze,Liao, Weike,Xu, Chen,Fu, Baolin,Ren, Jianguo,Gu, Yucheng,Gong, Ping
, p. 840 - 850 (2013/12/04)
A series of 4-(2-fluorophenoxy)-2-(1H-tetrazol-1-yl)pyridines bearing semicarbazone moieties were synthesized and evaluated for their in vitro antitumor potency. Some of the compounds (10b, 10c, 10e-10h, 10m-10p, 10r, and 11b) exhibited moderate to excellent antitumor activity as compared to sorafenib and PAC-1, as well as low levels of toxicity toward the human fetal lung fibroblast cell line WI-38. The most promising compound 10p (IC50 = 0.08, 0.36, 0.97 μM) was 45.1-, 6.1-, and 2.4-fold more active than sorafenib (IC50 = 3.61, 2.19, 2.32 μM), and 17, 3.2, and 2.9 times better than PAC-1 (IC50 = 1.36, 1.17, 2.83 μM) against three cancer cell lines (HT-29, H460, and MKN-45), respectively. In addition, further studies examining enzymatic activity suggested that the marked pharmacological activity observed might be ascribed to an inhibitory action against CRAf kinase. A series of 4-(2-fluorophenoxy)-2-(1H-tetrazol-1-yl)pyridines bearing semicarbazone moieties were synthesized and evaluated for their cytotoxic activities in vitro. The most promising compound 10p was further examined for enzymatic activity, with the goal to investigate the molecular mechanisms of action.
The synthesis and antimycobacterial properties of 4-(substituted benzylsulfanyl)pyridine-2-carboxamides
Klimesova, Vera,Herzigova, Petra,Palat, Karel,Machacek, Milos,Stolarikova, Jirina,Dahse, Hans-Martin,Moellmann, Ute
, p. 90 - 103 (2013/09/24)
4-(Substituted benzylsulfanyl)pyridine-2-carboxamides 6 were synthesized by a three-step synthesis starting from 4-chloropyridine-2-carboxylic acid and substituted benzyl thiols, with the exception of nitroderivatives. The compounds were evaluated for their anti-TB activity against M. tuberculosis, non-tuberculous mycobacteria (M. kansasii and M. avium), and MDR strains of M. tuberculosis. The activities expressed as the minimum inhibitory concentration (MIC) fall into the range of 8-250 μmol/L. The substances exhibited similar activities against both sensitive and resistant strains. ARKAT-USA, Inc.
Light-Emitting Material
-
, (2009/08/18)
This invention pertains to light emitting materials comprising novel ortho-metalated transition metal complexes [C?N]2ML, comprising chelate monoionic ligands (L), also called ancillary ligands. It has been surprisingly found that when the ancillary ligand comprises a substituted aromatic ring bearing a substituent possessing adequate electron-donating properties, said ligand (L) advantageously participates in the emission process, significantly shifting emission towards higher energies (blue-shift) and enabling appreciable improvement of the emission efficiency of complexes [C?N]2ML. Still objects of the invention are the use of said light emitting materials and organic light emitting device comprising said light emitting material.
Sequence selective dual-emission detection of (i, i + 1) bis-phosphorylated peptide using diazastilbene-type Zn(ii)-Dpa chemosensor
Ishida, Yoshiyuki,Inoue, Masa-Aki,Inoue, Tomonori,Ojida, Akio,Hamachi, Itaru
supporting information; experimental part, p. 2848 - 2850 (2009/12/01)
This paper describes a new fluorescent chemosensor for phosphorylated peptide, which comprises a rigid trans-4,4′-diazastilbene and two Zn(ii)-Dpa (2,2′-dipicolylamine) units; this chemosensor sequence-selectively binds to a (i, i + 1) bis-phosphorylated peptide and displays a dual-emission fluorescence change.
Preparation and in-vitro evaluation of 4-benzylsulfanylpyridine-2- carbohydrazides as potential antituberculosis agents
Herzigova, Petra,Klimesova, Vera,Palat, Karel,Kaustova, Jarmila,Dahse, Hans-Martin,Moellmann, Ute
scheme or table, p. 394 - 404 (2009/11/30)
A set of 4-benzylsulfanylpyridine-2-carbohydrazides was synthesized and evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, non-tuberculous mycobacteria, and multidrug-resistant M. tuberculosis. The activities expressed as the minimum inhibitory concentration (MIC) fall into a range of 2 to 125 μmol/L, most often 4 to 32 μmol/L. The results revealed that the substituents on the benzyl moiety do not influence the antimycobacterial efficacy. The substances exhibited similar activities against sensitive and resistant strains of M. tuberculosis. Furthermore, compounds show low antiproliferative effect and cytotoxicity.
