147-47-7Relevant academic research and scientific papers
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.
A facile synthesis of 2,2,4-trisubstituted-1,2-dihydroquinolines catalyzed by zinc triflate under solvent-free conditions
Kundu, Dhiman,Kundu, Shrishnu Kumar,Majee, Adinath,Hajra, Alakananda
, p. 1186 - 1190 (2008)
An efficient process has been developed for the synthesis of 2,2,4-trisubstituted-1,2-dihydroquinolines in good yields through a simple one-pot condensation between anilines and ketones in the presence of zinc triflate as a catalyst at room temperature under solvent-free conditions.
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.
Synthesis of 2,2,4-trimethyl-1,2-dihydroquinolines over metal-modified 12-tungstophosphoric acid-supported γ-Al2O3 catalyst
Krishna, Bandarupalli,Roy, Sounak
, p. 4061 - 4077 (2020)
In spite of having significant pharmacological importance, scalable synthesis of 2,2,4-trimethyl-1,2-H-dihydroquinoline (TMQ) is always being cumbersome due to harmful solvents, drastic reaction conditions, and high recovery cost of homogeneous catalysts. Heterogeneous catalytic condensation of aniline with acetone was employed here to synthesize TMQ. As efficient materials, Zn2+-, Sn2+-, and Cu2+-exchanged tungstophosphoric acid (TPA) supported on γ-Al2O3 was synthesized by microwave-assisted hydrothermal method. The synthesized catalysts were thoroughly characterized by XRD, Raman, FE-SEM, etc. and were screened for condensation reaction. Among the metal-exchanged catalysts, Zn0.5TPA/Al2O3 showed highest aniline conversion with the highest yield of TMQ up to three consecutive cycles. The acidic sites over the catalysts were probed by pyridine-adsorbed FT-IR spectra and NH3-TPD studies. The reaction conditions were optimized, and plausible reaction mechanistic pathway was derived from FT-IR and GC–MS data.
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.
Novel facile synthesis of 2,2,4 substituted 1,2-dihydroquinolines via a modified Skraup reaction
Theoclitou, Maria-Elena,Robinson, Leslie A.
, p. 3907 - 3910 (2002)
A variety of 2,2,4 substituted 1,2-dihydroquinolines were synthesized from substituted anilines or aminoheterocycles and the corresponding ketones in good yield via the use of lanthanide catalysts and microwave technology. This method can be readily applied to the general synthesis of combinatorial libraries of dihydroquinolines.
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.
COMPOUNDS TARGETING DUAL G-QUADRUPLEX DNA AND STAT3
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Page/Page column 31; 34; 36, (2021/01/23)
The present invention relates to novel quinazoline compounds having the formula (I) or (II): (I) (II). The compounds are active both as stabilizers of G-quadruplex DNA structures and as inhibitors of STAT3 phosphorylation. The disclosed compounds are useful in medical treatment, such as the treatment of cancer.
Anti-aging agent TMQ and preparation method thereof
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Paragraph 0021-0025, (2018/06/21)
The invention provides an anti-aging agent TMQ and a preparation method thereof. The preparation method comprises preparing the anti-aging agent TMQ for rubber from aniline and acetone (or isopropylideneacetone) as raw materials in the presence of a catalyst through a one-step method. The catalyst comprises a titanate catalyst. The anti-aging agent TMQ for rubber is prepared through the preparation method. The preparation method utilizes a batch or continuous production process. A single-pass conversion of aniline is 80% or more. The content of the product TMQ effective bodies (such as dimer,trimer and tetramer) is 65% to 75%. Compared with the prior art, the preparation method utilizing the titanate catalyst to prepare the rubber anti-aging agent TMQ is an eco-friendly method having theadvantages of simple processes, low catalyst consumption, low cost and high effective body content.
