147-47-7Relevant articles and documents
Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization
?hlund, Daniel,Akhunzianov, Almaz,Br?nnstr?m, Kristoffer,Chand, Karam,Chorell, Erik,Deiana, Marco,Doimo, Mara,Hedenstr?m, Mattias,Jamroskovic, Jan,Kasho, Kazutoshi,Kumar, Rajendra,Mason, James E.,Medini, Paolo,Nath Das, Rabindra,Obi, Ikenna,Pourbozorgi, Parham L.,Sabouri, Nasim,Sulis Sato, Sebastian,Wanrooij, Sjoerd
, (2020)
The signal transducer and activator of transcription 3 (STAT3) protein is a master regulator of most key hallmarks and enablers of cancer, including cell proliferation and the response to DNA damage. G-Quadruplex (G4) structures are four-stranded noncanonical DNA structures enriched at telomeres and oncogenes' promoters. In cancer cells, stabilization of G4 DNAs leads to replication stress and DNA damage accumulation and is therefore considered a promising target for oncotherapy. Here, we designed and synthesized novel quinazoline-based compounds that simultaneously and selectively affect these two well-recognized cancer targets, G4 DNA structures and the STAT3 protein. Using a combination of in vitro assays, NMR, and molecular dynamics simulations, we show that these small, uncharged compounds not only bind to the STAT3 protein but also stabilize G4 structures. In human cultured cells, the compounds inhibit phosphorylation-dependent activation of STAT3 without affecting the antiapoptotic factor STAT1 and cause increased formation of G4 structures, as revealed by the use of a G4 DNA-specific antibody. As a result, treated cells show slower DNA replication, DNA damage checkpoint activation, and an increased apoptotic rate. Importantly, cancer cells are more sensitive to these molecules compared to noncancerous cell lines. This is the first report of a promising class of compounds that not only targets the DNA damage cancer response machinery but also simultaneously inhibits the STAT3-induced cancer cell proliferation, demonstrating a novel approach in cancer therapy.
The: P -toluenesulfonic acid catalyzed single pot synthesis of tetracyclic 1,2-dihydroquinolines: A metal free approach
Hajare, Anil K.,Jagdale, Arun R.,Shenoy, G. Gautham,Sinha, Neelima
, p. 4888 - 4890 (2016)
A simple, convenient and efficient p-toluenesulfonic acid catalyzed tandem reaction of aliphatic ketones with substituted anilines towards the synthesis of polysubstituted 1,2-dihydroquinolines has been developed. The ready availability of the catalyst, operational simplicity, cost effectiveness of the process and excellent regioselectivity mark some of the highlights of this methodology.
Mild and convenient synthesis of 1,2-dihydroquinolines from anilines and acetone catalyzed by ytterbium(III) triflate in ionic liquids
Li, Yongshu,Wu, Chunlei,Huang, Jianliang,Su, Weike
, p. 3065 - 3073 (2006)
A mild, convenient, and efficient process has been developed for the synthesis of 2,2,4-trimethyl-1,2-dihydroquinolines by the reaction of anilines with acetone catalyzed by ytterbium(III) triflate [Yb(OTf)3] in ionic liquids. The catalyst and ionic liquids can be easily recovered and reused, making this method friendly and environmentally acceptable. Copyright Taylor & Francis Group, LLC.
Elliot,Yates
, p. 1287 (1961)
Discovery of Novel Potent Reversible and Irreversible Myeloperoxidase Inhibitors Using Virtual Screening Procedure
Soubhye, Jalal,Chikh Alard, Ibaa,Aldib, Iyas,Prévost, Martine,Gelbcke, Michel,De Carvalho, Annelise,Furtmüller, Paul G.,Obinger, Christian,Flemmig, J?rg,Tadrent, Sara,Meyer, Franck,Rousseau, Alexandre,Nève, Jean,Mathieu, Véronique,Zouaoui Boudjeltia, Karim,Dufrasne, Fran?ois,Van Antwerpen, Pierre
, p. 6563 - 6586 (2017)
The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great interest in the development of new efficient and specific inhibitors. Here, we have performed a novel virtual screening procedure, depending on ligand-based pharmacophore modeling followed by structure-based virtual screening. Starting from a set of 727842 compounds, 28 molecules were selected by this virtual method and tested on MPO in vitro. Twelve out of 28 compounds were found to have an IC50 less than 5 μM. The best inhibitors were 2-(7-methoxy-4-methylquinazolin-2-yl)guanidine (28) and (R)-2-(1-((2,3-dihydro-1H-imidazol-2-yl)methyl)pyrrolidin-3-yl)-5-fluoro-1H-benzo[d]imidazole (42) with IC50 values of 44 and 50 nM, respectively. Studies on the mechanism of inhibition suggest that 28 is the first potent mechanism-based inhibitor and inhibits irreversibly MPO at nanomolar concentration.
Method for preparing 2,2,4-trimethyl-1,2-dihydroquinoline by using ionic liquid
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Paragraph 0017-0035, (2021/09/29)
The invention discloses a method for preparing 2,2,4-trimethyl-1,2-dihydroquinoline by using ionic liquid, belonging to the field of organic chemical synthesis. According to the method, 2,2,4-trimethyl-1,2-dihydroquinoline is prepared by taking aniline and 4-methyl-2,3-pentanedione as raw materials and taking ionic liquid which is good in thermal stability, difficult to volatilize and recyclable as a catalyst and a solvent. The method does not use any toxic and harmful catalyst, is simple and convenient to operate, simple in post-treatment, mild in reaction conditions and high in yield, and is a novel green method for synthesizing the 2,2,4-trimethyl-1,2-dihydroquinoline.
Synthesis of 2,2,4-trimethyl-1,2-H-dihydroquinoline (TMQ) over selected organosulfonic acid silica catalysts: Selectivity aspects
Nowicki,Jaroszewska,Nowakowska-Bogdan,Szmato?a,I?owska
, p. 94 - 103 (2018/05/28)
This paper presents investigation on the synthesis of 2,2,4-trimethyl-1,2-H-dihydroquinoline (TMQ) as a result of the reaction of aniline and both acetone and mesityl oxide in the presence of selected sulfonic acid silica catalysts. Condensation of aniline with acetone is very complex process with the formation of significant number of side products, both desirable and undesirable considering the final product (TMQ). In acidic conditions and elevated reaction temperature the reactivity of main raw materials (aniline, acetone) is significantly high, what causes the formation of many side by-products lowering the selectivity of this reaction. In this paper the reaction of aniline with acetone in the presence of heterogeneous acidic silica catalysts were investigated in more detail and discussed. The results were confirmed by GC/MS analysis, that the presence of TMQ isomers and other by-products significantly affected the formation of final product. The formation of previously not described structural isomer of TMQ has been also demonstrated.
