4053-50-3

Upstream product

• 104-94-9 4-methoxy-aniline 
• 67-64-1 acetone 
• 141-79-7 4-methyl-pent-3-en-2-one 

Downstream Products

• 244052-68-4 1-(6-methoxy-4-methylquinazolin-2-yl)guanidine 
• 35053-12-4 1-acetyl-6-methoxy-4-phenyl-1,2,3,4-tetrahydro-2,2,4-trimethylquinoline 
• 487065-13-4 1-acetyl-6-hydroxy-4-phenyl-1,2,3,4-tetrahydro-2,2,4-trimethylquinoline 
• 135692-39-6 4,5-dihydro-4,4-dimethyl-8-methoxy-2,3-dithiolo<5,4c>quinoline-1-thione 

Relevant academic research and scientific papers

Determination of the Synthetic Antioxidant Ethoxyquin and Its Metabolites in Fish and Fishery Products Using Liquid Chromatography-Fluorescence Detection and Stable-Isotope Dilution Analysis-Liquid Chromatography-Tandem Mass Spectrometry

The use of the synthetic antioxidant ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline, EQ) as a flame retardant in fish meal transported by sea is required by international authorities to prevent self-ignition. Because of extensive carry-over within the food chain, selective and sensitive analytical methods are required for investigations on human exposure and the safety of EQ and its metabolites. Therefore, a simple, fast, and rugged liquid-chromatography (LC) method was developed for the detection of EQ and its metabolites in fish and fishery products after liquid-liquid extraction using QuEChERS. For screening purposes, a fluorescence detector was used (LC-FLD) with the EQ-analogue methoxyquin serving as an internal standard. For stable-isotope dilution analysis by liquid chromatography-tandem mass spectrometry (SIDA-LC-MS/MS), deuterated analogues of EQ and its metabolites were synthesized for the first time and allowed for sensitive quantification and thus confirmation of screening results. Both methods were validated and successfully applied to commercially available fish samples.

Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization

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.

COMPOUNDS TARGETING DUAL G-QUADRUPLEX DNA AND STAT3

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.

Synthesis of 2,2,4-trimethyl-1,2-dihydroquinolines over metal-modified 12-tungstophosphoric acid-supported γ-Al2O3 catalyst

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.

New fluorescence-based high-throughput screening assay for small molecule inhibitors of tyrosyl-DNA phosphodiesterase 2 (TDP2)

Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (TOP2) mediated DNA damages and causes resistance to TOP2-targeted cancer therapy. Inhibiting TDP2 could sensitize cancer cells toward TOP2 inhibitors. However, potent TDP2 inhibitors with favorable physicochemical properties are not yet reported. Therefore, there is a need to search for novel molecular scaffolds capable of inhibiting TDP2. We report herein a new simple, robust, homogenous mix-and-read fluorescence biochemical assay based using humanized zebrafish TDP2 (14M_zTDP2), which provides biochemical and molecular structure basis for TDP2 inhibitor discovery. The assay was validated by screening a preselected library of 1600 compounds (Z′ ≥ 0.72) in a 384-well format, and by running in parallel gel-based assays with fluorescent DNA substrates. This library was curated via virtual high throughput screening (vHTS) of 460,000 compounds from Chembridge Library, using the crystal structure of the novel surrogate protein 14M_zTDP2. From this primary screening, we selected the best 32 compounds (2% of the library) to further assess their TDP2 inhibition potential, leading to the IC50 determination of 10 compounds. Based on the dose-response curve profile, pan-assay interference compounds (PAINS) structure identification, physicochemical properties and efficiency parameters, two hit compounds, 11a and 19a, were tested using a novel secondary fluorescence gel-based assay. Preliminary structure-activity relationship (SAR) studies identified guanidine derivative 12a as an improved hit with a 6.4-fold increase in potency over the original HTS hit 11a. This study highlights the importance of the development of combination approaches (biochemistry, crystallography and high throughput screening) for the discovery of TDP2 inhibitors.

The catalytic enantioselective synthesis of tetrahydroquinolines containing all-carbon quaternary stereocenters via the formation of aza-ortho-xylylene with 1,2-dihydroquinoline as a precursor

Tetrahydroquinolines (THQs) with an all-carbon quaternary stereocenter were effectively obtained via the in situ formation of aza-ortho-xylylene (AOX) with easily accessible 1,2-dihydroquinolines as precursors. The reaction was rationalized with chiral phosporic acid to afford chiral THQs with high yield and excellent enantioselectivity.

Enantioselective Organocatalytic Transfer Hydrogenation of 1,2-Dihydroquinoline through Formation of Aza-o-xylylene

A new way of forming the aza-o-xylylene with easily accessible 1,2-dihydroquinolines as precursor has been developed. The presence of an electron-donating group at the proper position of 1,2-dihydroquinoline was crucial for protonation of the alkene through dearomatization with a simple Bronsted acid. The in situ forming reactive intermediate was trapped with Hantzsch ester to afford tetrahydroquinolines in excellent yield and enantioselectivity.

Ceric ammonium nitrate: An efficient catalyst for one-pot synthesis of 2,2,4-trimethyl-1,2-dihydroquinolines

Ceric ammonium nitrate (CAN) catalyzed the one-pot synthesis of 2,2,4-trirnethyl-1,2-dihydroquinoline derivatives from substituted anilines and acetone via a modified Skraup reaction. The methodology was used to synthesize a novel dihydroquinoline-based compound derived from an anti-inflammatory agent nimesulide.

A facile synthesis of 2,2,4-trisubstituted-1,2-dihydroquinolines catalyzed by zinc triflate under solvent-free conditions

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.

Identification of substituted 6-amino-4-phenyltetrahydroquinoline derivatives: Potent antagonists for the follicle-stimulating hormone receptor

Substituted 6-amino-4-phenyl-tetrahydroquinoline derivatives are described that are antagonists for the Gs-protein-coupled human follicle-stimulating hormone (FSH) receptor. These compounds show high antagonistic efficacy in vitro using a CHO c