83-54-5

Usage

Uses

Used in Pharmaceutical Industry:
1-Methyl-4-quinolone is used as a building block for the synthesis of various drugs due to its antimicrobial and antiviral properties, contributing to the development of new therapeutic agents.
Used in Cancer Treatment Research:
1-Methyl-4-quinolone is used as a potential therapeutic agent for treating cancer, given its unique chemical structure that allows for targeted interventions in disease processes.
Used in Alzheimer's Disease Research:
1-methyl-4-quinolone is also being studied for its potential in treating Alzheimer's disease, leveraging its chemical properties to address the complex biological challenges associated with this condition.
Used in Medicinal Chemistry Research:
1-Methyl-4-quinolone serves as a valuable tool in medicinal chemistry, facilitating the exploration of new drug candidates and deepening our understanding of molecular interactions.
Used in Fluorescent Probe Development:
As a fluorescent probe, 1-Methyl-4-quinolone is utilized for detecting and imaging biological molecules and processes, enhancing the precision and efficiency of biological research and diagnostics.

InChI:InChI=1/C10H9NO/c1-11-7-6-10(12)8-4-2-3-5-9(8)11/h2-7H,1H3

Upstream product

• 46000-25-3 4-methylthioisoquinoline 
• 77-78-1 dimethyl sulfate 
• 3334-56-3 N-methyl-N-(2-[hydroxycarbonyl]ethyl)aniline 
• 607-31-8 4-methoxyquinoline 
• 64275-22-5 1-methyl-4-cyano-quinolinium iodide 
• 55577-52-1 4-methoxy-1-methyl-quinolinium; iodide 
• 611-36-9 quinolin-4-ol 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 512-56-1 trimethyl phosphite 
• 529-37-3 4(1H)-quinolinone 
• 78-40-0 triethyl phosphate 
• 80-48-8 methyl p-toluene sulfonate 
• 80-40-0 ethyl ester of p-toluenesulfonic acid 
• 38746-10-0 1,8-dimethylquinolinium methylsulfate 

Downstream Products

• 6291-51-6 1-methyl-1H-quinoline-4-thione 
• 24220-95-9 1-Methyl-3-nitro-4-chinolon 
• 875-63-8 N-methyl-cis-decahydroquinoline 
• 142671-75-8 2-(1,3-dithian-2-yl)-2-(α-hydroxybenzyl)-1-methyl-quinolin-4(1H)-one 
• 142671-82-7 2-(1,3-dithian-2-yl)-2-(α-hydroxybenzylidene)-1-methyl-2,3-dihydroquinolin-4(1H)-one 
• 139710-86-4 2-butyl-1-methyl-4-quinolone 
• 139710-92-2 2-butyl-1-methyl-2,3-dihydroquinolin-4(1H)-one 
• 139710-77-3 2-(α-hydroxybenzyl)-1-methyl-4-quinolone 
• 139710-85-3 2--1-methyl-4-quinolone 
• 6760-40-3 1,2-dimethyl-1,4-dihydroquinolin-4-one 
• 142671-77-0 2,4-dimethyl-1,2,3,4-tetrahydroquinolin-1-one 
• 619-73-8 4-nitrobenzyl chloride 
• 139710-78-4 2-(α-hydroxy-4-nitrobenzyl)-1-methyl-4-quinolone 
• 139710-91-1 1-methyl-2-(1-methyl-4-oxo-1,2,3,4-tetrahydro-2-quinolyl)-4-quinolone 

Relevant academic research and scientific papers

Evaluation of a simple and novel fluorescent anion sensor, 4-quinolone, and modification of the emission color by substitutions based on molecular orbital calculations

4-Quinolone (4-QO) was evaluated as a simple and novel fluorescent anion sensor, and the modification of its emission color was carried out. The series of 4-QO derivatives having molecular orbitals with different energy levels was designed by substitutions at the 6 and 7 positions based on the molecular orbital calculations. All derivatives showed drastic fluorescence enhancements in the presence of F- via the intramolecular charge transfer mechanism, and the successful modification of the emission color was achieved. The anion-induced emission colors of these derivatives as well as their binding affinities for F- could be predicted by ab initio quantum chemical calculations, indicating that the present calculations are useful in designing new anion sensors.

Conjugate Addition Routes to 2-Alkyl-2,3-dihydroquinolin-4(1H)-ones and 2-Alkyl-4-hydroxy-1,2-dihydroquinoline-3-carboxylates

Under CuBr·SMe2/PPh3 catalysis (5/10 mol-%) RMgCl (R = Me, Et, nPr, CH=CH2, nBu, iBu, nC5H11, cC6H11, Bn, CH2Bn, nC11H23) readily (–78 °C) undergo 1,4-addition to Cbz or Boc protected quinolin-4(1H)-ones to provide 2-alkyl-2,3-dihydroquinolin-4(1H)-ones (14 examples, 54–99 % yield). Asymmetric versions require AlEt3 to Boc-protected ethyl 6-substituted 4(1H)-quinolone-3-carboxylates (6-R group = all halogens, n/i/t-alkyls, CF3) and provide 61–91 % yield, 30–86 % ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76–86 % ee). Additions of AlMe3 or Al(nC8H17)3 provide ≈ 45 and ≈ 75 % ee on addition to the parent (6-R = H). Ligand (S)-(BINOL)P–N(CHPh2)(cC6H11) provides the highest ee values engendering addition to the Si face of the 4(1H)-quinolone-3-carboxylate. Allylation and deprotection of a representative 1,4-addition product example confirm the facial selectivity (X-ray crystallography).

Iodine/persulfate-promoted site-selective direct thiolation of quinolones and uracils

A simple and general method for direct thiolation of 4-quinolones with disulfides or thiols under I2/K2S2O8 system has been developed. Under the optimal conditions, the C–S bond coupling can take place effectively with good to decent yields and excellent regioselectivity of the S-linked products. The established metal-free site-selective approach was also applicable to transform a range of uracil substrates to the thio-substituted products under mild conditions. Further transformation to the sulfone derivatives can be conveniently performed in one-pot. These easy-to-handle protocols represent a useful and interesting synthetic alternative with good substrate scope and functional group compatibility.

Highly Enantioselective Catalytic Addition of Grignard Reagents to N-Heterocyclic Acceptors

General methods to prepare chiral N-heterocyclic molecular scaffolds are greatly sought after because of their significance in medicinal chemistry. Described here is the first general catalytic methodology to access a wide variety of chiral 2- and 4-substituted tetrahydro-quinolones, dihydro-4-pyridones, and piperidones with excellent yields and enantioselectivities, utilizing a single catalyst system.

Aerobic C–C Bond Cleavage of Indoles by Visible-Light Photoredox Catalysis with Ru(bpy)32+

Photoredox catalysis with Ru(bpy)32+ (2,2′-bipyridine) has been used to enable the activation of oxygen in the aerobic C–C cleavage/oxygenation reaction of indoles. A number of indole substrates that contain various functional groups were successfully employed in the reaction to give a wide range of ortho-aminobenzaldehyde derivatives. These products can then be used as versatile building blocks for further synthetic modifications. Mechanistic studies suggest that the reaction proceeds through a radical pathway.

Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands

Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.

Unraveling innate substrate control in site-selective palladium-catalyzed C-H heterocycle functionalization

Understanding the regioselectivity of C-H activation in the absence of directing groups is an important step towards the design of site-selective C-H functionalizations. The Pd(ii)-catalyzed direct arylation of chromones and enaminones provides an intriguing example where a simple substitution leads to a divergence in substrate-controlled site-selectivity. We describe computational and experimental studies which reveal this results from a switch in mechanism and therefore the selectivity-determining step. We present computational results and experimentally measured kinetic isotope effects and labelling studies consistent with this proposal. The C-H activation of these substrates proceeds via a CMD mechanism, which favors more electron rich positions and therefore displays a pronounced kinetic selectivity for the C3-position. However, C2-selective carbopalladation is also a competitive pathway for chromones so that the overall regiochemical outcome depends on which substrate undergoes activation first. Our studies provide insight into the site-selectivity based on the favorability of two competing CMD and carbopalladation processes of the substrates undergoing coupling. This model can be utilized to predict the regioselectivity of coumarins which are proficient substrates for carbopalladation. Furthermore, our model is able to account for the opposite selectivities observed for enaminone and chromone, and explains how a less reactive coupling partner leads to a switch in selectivity.

Synthesis of bridged benzazocines and benzoxocines by a titanium-catalyzed double-reductive umpolung strategy

A sequence of two titanium(III)-catalyzed reductive umpolung reactions is reported that allows the rapid construction of benzazo- and benzoxozine building blocks. The first step is a reductive cross-coupling of quinolones or chromones with Michael acceptors. This reaction proceeds with complete syn-selectivity for the quinolone functionalization while the anti-diastereomers are obtained as the major products from chromones. With different reaction conditions, the stereochemical outcome can be altered to afford the syn-chromanone products as well. A subsequent reductive ketyl radical cyclization forges the tricyclic title compounds in good yields. A stereochemical model explaining the observed stereoselectivities is provided and the product configurations were unambiguously verified by X-ray analyses and 2D NMR spectroscopic experiments.

Synthesis of 4-quinolones through nickel-catalyzed intramolecular amination on the β-carbon of o-(N-alkylamino)propiophenones

o-(N-Alkylamino)propiophenones are converted into 4-quinolones in the presence of chlorobenzene, potassium phosphate, morpholine, and nickel(0) catalyst. The reaction proceeds through the nickel-catalyzed formation of β-enaminones from o-(N-alkylamino)propiophenones and morpholine, followed by the intramolecular transamination. Georg Thieme Verlag Stuttgart · New York.

Discovery of Potent, orally bioavailable phthalazinone bradykinin B1 receptor antagonists

The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic amine moiety leading to potent series of 2-oxopiperazines. The suboptimal pharmacokinetics and physicochemical properties of the oxopiperazine sulfonamides led us to seek B1 antagonists with improved druglike properties. Using a pharmacophore model containing a bicyclic amine as anchor, we designed a series of amide antagonists with targeted physicochemical properties. This approach led to a novel series of potent phthalazinone B1 antagonists, where we successfully replaced a sulfonamide acceptor with a cyclic carbonyl unit. SAR studies revealed compounds with subnanomolar B1 binding affinity. These compounds demonstrate excellent cross-species PK properties with high oral bioavailability and potent activity in a rabbit biochemical challenge pharmacodynamic study.