21901-41-7Relevant articles and documents
Synthesis, docking study and kinase inhibitory activity of a number of new substituted pyrazolo[3,4-c]pyridines
Sklepari, Meropi,Lougiakis, Nikolaos,Papastathopoulos, Athanasios,Pouli, Nicole,Marakos, Panagiotis,Myrianthopoulos, Vassilios,Robert, Thomas,Bach, Stéphane,Mikros, Emmanuel,Ruchaud, Sandrine
, p. 66 - 81 (2017/01/06)
A series of new pyrazolo[3,4-c]pyridines bearing various 1, 3, 5 or 1, 3, 7 pattern substitutions, were designed and synthesized. Some of them showed interesting inhibitory activity mainly against glycogen synthase kinase 3 (GSK3)α/β as well as against cdc2-like kinases 1 (CLK1) and dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), with good selectivity and remarkable structure-activity relationships (SARs), without being cytotoxic. Molecular simulations in correlation with biological data revealed the importance of the existence of N1-H as well as the absence of a bulky 7-substituent.
Ethanol compound used as FGFR inhibitor
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, (2017/03/17)
The invention discloses an ethanol compound used as a FGFR inhibitor. The invention provides the compound as shown in a formula I which is described in the specification or a pharmaceutically acceptable salt thereof, a preparation method for the compound and application of the compound as a medicine to treatment of cancers.
Novel pyrazolopyridine derivatives as potential angiogenesis inhibitors: Synthesis, biological evaluation and transcriptome-based mechanistic analysis
Michailidou, Maria,Giannouli, Vassiliki,Kotsikoris, Vasilios,Papadodima, Olga,Kontogianni, Georgia,Kostakis, Ioannis K.,Lougiakis, Nikolaos,Chatziioannou, Aristotelis,Kolisis, Fragiskos N.,Marakos, Panagiotis,Pouli, Nicole,Loutrari, Heleni
, p. 143 - 157 (2016/06/09)
Modified purine derivatives exemplified by pyrazolopyrimidines have emerged as highly selective inhibitors of several angiogenic receptor tyrosine kinases. Herein, we designed and synthesized a new series of substituted pyrazolopyridines and explored their ability to influence crucial pro-angiogenic attributes of endothelial cells. Four of the synthesized compounds, possessing analogous substitution pattern, were found able to inhibit at low micromolar concentrations endothelial cell proliferation, migration and differentiation, constitutively or in response to Vascular Endothelial Growth Factor (VEGF) and to attenuate VEGF-induced phosphorylation of VEGF receptor-2 and downstream kinases AKT and ERK1/2. Administration of effective compounds in mice delayed the growth of syngeneic Lewis lung carcinoma transplants and reduced tumor microvessel density, without causing toxicity. Genome-wide microarray and gene ontology analyses of treated endothelial cells revealed derivative 18c as the most efficient modulator of gene expression and mitotic cell cycle/cell divisiong along with ? cholesterol biosynthesis? as the most significantly altered biological processes.
The discovery of new cytotoxic pyrazolopyridine derivatives
Giannouli, Vassiliki,Lougiakis, Nikolaos,Kostakis, Ioannis K.,Pouli, Nicole,Marakos, Panagiotis,Skaltsounis, Alexios-Leandros,Nam, Sangkil,Jove, Richard,Horne, David,Tenta, Roxane,Pratsinis, Harris,Kletsas, Dimitris
, p. 5229 - 5233 (2016/11/02)
A number of new 3,7-disubstituted pyrazolo[3,4-c]pyridines have been designed and synthesized from suitable 2-aminopyridines. The antiproliferative activity of the derivatives was determined against the pancreatic MIA PaCa-2 and ovarian SCOV3 cancer cell-lines. IC50values of the most promising analogue 46 lie in the submicromolar or low micromolar range. Furthermore, compound 46 shows similar inhibitory activities against DU145, A2058 and PC-3 cancer cells, blocks the cell cycle at the G0/G1phase and induce apoptosis, as determined by the appearance of apoptotic nuclei.
Synthesis of some fluorine-containing pyridinealdoximes of potential use for the treatment of organophosphorus nerve-agent poisoning
Timperley, Christopher M.,Banks, R. Eric,Young, Ian M.,Haszeldine, Robert N.
scheme or table, p. 541 - 547 (2011/09/15)
Fluoroheterocyclic aldoximes were screened as therapeutic agents for the treatment of anticholinesterase poisoning. 2-Fluoropyridine-3- and -6-aldoxime, and 3-fluoropyridine-2- and -4-aldoxime, were synthesised. Attempts to obtain 3,5,6-trifluoropyridine-2,4-bis(aldoxime) and -2-aldoxime, however, proved unsuccessful. Pentafluorobenzaldoxime was prepared by oximation of pentafluorobenzaldehyde. Acid dissociation constants (pKa) and second-order rate constants (kox-) of the fluorinated pyridinealdoximes towards sarin were measured. 2,3,5,6-Tetrafluoropyridine-4- aldoxime had the best profile: its kox- approached that of the therapeutic oxime P2S (310 vs. 120 l mol-1 min-1), but its higher pKa (9.1 vs. 7.8) fell short of the target figure of 8 required for reactivation of inhibited acetylcholinesterase in vivo. N-alkylation of the fluorinated pyridine-aldoximes may reduce their pK a nearer to 8 and enhance their therapeutic potential. Crown Copyright
THE NITROPYRIDINYL ETHYLENEIMINE COMPOUND, THE PHARMACEUTICAL COMPOSITION CONTAINING IT, THE PREPARATION METHOD AND USE THEREOF
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, (2011/10/10)
The present invention discloses a nitropyridinyl ethyleneimine compound as shown in the formula I and a preparation method of the same, as well as use of the compound in manufacture of a prodrug and in manufacture of a drug for treating a tumor.
Heterocyclic FXR binding compounds
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Page/Page column 33, (2008/06/13)
The present invention relates to compounds which bind to the NR1H4 receptor (FXR) and act as agonists or partial agonists of the NR1H4 receptor (FXR). The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds, and to a process for the synthesis of said compounds.
KINASE INHIBITORS
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Page/Page column 12, (2010/11/27)
The present invention provides kinase inhibitors of Formula (I). Wherein R1, R2, X and Z are as described herein, or a pharmaceutically acceptable salt thereof.
