72407-17-1

Usage

Uses

Used in Pharmaceutical Synthesis:
2,4-dichloro-6,7-dimethoxy-quinoline is utilized as a key intermediate in the synthesis of various pharmaceuticals due to its unique structural features and reactivity. Its presence in the molecular framework can enhance the potency and selectivity of resulting drug candidates.
Used in Agrochemical Synthesis:
In the agrochemical industry, 2,4-dichloro-6,7-dimethoxy-quinoline serves as a building block for the development of new pesticides and herbicides. Its incorporation can lead to improved efficacy and selectivity in controlling agricultural pests and weeds.
Used in Anti-cancer Research:
2,4-dichloro-6,7-dimethoxy-quinoline is explored as a potential anti-cancer agent, with studies focusing on its ability to target and inhibit the growth of cancer cells. Its pharmacological properties make it a candidate for further research into novel cancer therapeutics.
Used in Anti-inflammatory Applications:
2,4-dichloro-6,7-dimethoxy-quinoline is also considered for its anti-inflammatory potential, where it may be used to alleviate inflammation and associated symptoms in various conditions. Its capacity to modulate inflammatory responses is an area of ongoing investigation.
Used in Drug Development:
2,4-dichloro-6,7-dimethoxy-quinoline is employed as a structural component in the development of new drugs, leveraging its biological activity and reactivity to create molecules with enhanced therapeutic effects and fewer side effects.

Upstream product

• 141-82-2 malonic acid 
• 6315-89-5 3,4-dimethoxyaniline 
• 412335-39-8 2,4-dihydroxy-6,7-dimethoxyquinoline 
• 412335-39-8 4-hydroxy-6,7-dimethoxyquinolin-2(1H)-one 

Downstream Products

• 933609-72-4 4-chloro-6,7-dimethoxyquinolin-2(1H)-one 
• 100122-02-9 4-chloro-6,7-dimethoxy-2-methylquinoline 
• 1616295-09-0 2-cyclopropyl-6,7-dimethoxy-4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-quinoline 

Relevant academic research and scientific papers

Detailed Exploration around 4-Aminoquinolines Chemical Space to Navigate the Lysine Methyltransferase G9a and DNA Methyltransferase Biological Spaces

Epigenetic regulators that exhibit aberrant enzymatic activities or expression profiles are potential therapeutic targets for cancers. Specifically, enzymes responsible for methylation at histone-3 lysine-9 (like G9a) and aberrant DNA hypermethylation (DNMTs) have been implicated in a number of cancers. Recently, molecules bearing a 4-aminoquinoline scaffold were reported as dual inhibitors of these targets and showed a significant in vivo efficacy in animal models of hematological malignancies. Here, we report a detailed exploration around three growing vectors born by this chemotype. Exploring this chemical space led to the identification of features to navigate G9a and DNMT1 biological spaces: not only their corresponding exclusive areas, selective compounds, but also common spaces. Thus, we identified from selective G9a and first-in-class DNMT1 inhibitors, >1 log unit between their IC50 values, with IC50 50 50 nM for both targets (e.g., 13). Their ADME/Tox profiling and antiproliferative efficacies, versus some cancer cell lines, are also reported.

NOVEL COMPOUNDS FOR USE IN CANCER

It relates to the compounds of formula (I), or their pharmaceutically or veterinary acceptable salts, or their stereoisomers or mixtures of stereoisomers, wherein X, L,R1, R 2, and R 3 are as defined herein, which are cancer cell differentiation inducing agents. It also relates to pharmaceutical or veterinary compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of cancer, in particular by cell differentiation therapy.

Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity

Plasmodium falciparum HKMTs (PfHKMTs) play a key role in controlling Plasmodium gene expression and represent exciting new anti-malarial epigenetic targets. Using an inhibitor series derived from the diaminoquinazoline HKMT inhibitory chemotype, we have previously identified compounds with highly promising antimalarial activity, including irreversible asexual cycle blood stage-independent cytotoxic activity at nM concentrations, oral efficacy in in vivo models of disease, and the unprecedented ability to reactivate dormant liver stage parasites (hypnozoites). However, future development of this series will need to address host versus parasite selectivity, where inhibitory activity against human G9a is removed from the lead compounds, while maintaining potent anti-Plasmodium activity. Herein, we report an extensive study of the SAR of this series against both G9a and P. falciparum. We have identified key SAR features which demonstrate that high parasite vs. G9a selectivity can be achieved by selecting appropriate substituents at position 2, 4 and 7 of the quinazoline ring. We have also, in turn, discovered that potent G9a inhibitors can be identified by employing a 6-carbon 'Nle mimic' at position 7. Together, this data suggests that while broadly similar, the G9a and potential PfHKMT target(s) binding pockets and/or binding modes of the diaminoquinazoline analogues exhibit clear and exploitable differences. Based on this, we believe this scaffold to have clear potential for development into a novel anti-malarial therapeutic.

Scaffold morphing leading to evolution of 2,4-diaminoquinolines and aminopyrazolopyrimidines as inhibitors of the ATP synthesis pathway

The success of bedaquiline as an anti-tubercular agent for the treatment of multidrug-resistant tuberculosis has validated the ATP synthesis pathway and in particular ATP synthase as an attractive target. However, limitations associated with its use in the clinic and the drug-drug interactions with rifampicin have prompted research efforts towards identifying alternative ATP synthesis inhibitors with differentiated mechanisms of action. A biochemical assay was employed to screen AstraZeneca's corporate compound collection to identify the inhibitors of mycobacterial ATP synthesis. The high-throughput screening resulted in the identification of 2,4-diaminoquinazolines as inhibitors of the ATP synthesis pathway. A structure-activity relationship for the quinazolines was established and the knowledge was utilized to morph the quinazoline core into quinoline and pyrazolopyrimidine to expand the scope of chemical diversity. The morphed scaffolds exhibited a 10-fold improvement in enzyme potency and over 100-fold improvement in selectivity against inhibition of mammalian mitochondrial ATP synthesis. These novel compounds were bactericidal and demonstrated growth retardation of Mycobacterium tuberculosis in the acute mouse model of tuberculosis infection.

5-Methoxyquinoline derivatives as a new class of EZH2 inhibitors

A series of quinoline derivatives was synthesized and biologically evaluated as Enhancer of Zeste Homologue 2 (EZH2) inhibitors. Structure-activity relationship (SAR) studies led to the discovery of 5-methoxy-2-(4-methyl-1,4-diazepan-1-yl)-N-(1-methylpiperidin-4-yl)quinolin-4-amine (5k), which displayed an IC50 value of 1.2 μM against EZH2, decreased global H3K27me3 level in cells and also showed good anti-viability activities against two tumor cell lines. Due to the low molecular weight and the fact that no quinoline derivative has been reported as an EZH2 inhibitor, this compound could serve as a lead compound for further optimization.

NOVEL COMPOUNDS AS DUAL INHIBITORS OF HISTONE METHYLTRANSFERASES AND DNA METHYLTRANSFERASES

It relates to the use of compounds of formula (I'), or their pharmaceutically or veterinary acceptable salts, or their stereoisomers or mixtures thereof, as anticancer agents and as agents for generating induced pluripotent stem cells. Compounds of formula (I'), wherein R2' is an alcoxy group, a hydrocarbon chain or a ring system, and R1, R3, and R4 are as defined herein, are dual inhibitors of histone methyltransferases and DNA methyltransferases. It also relates to the compounds of formula (I'), or their pharmaceutically or veterinary acceptable salts, or their stereoisomers or mixtures thereof, wherein R2' is phenyl or 5- to 6-membered heteroaromatic ring, both optionally fused to another rings (i.e., compounds of formula (I)). It also relates to pharmaceutical or veterinary compositions containing compounds of formula (I).

Syntheses and fluorescent properties of 6-methoxy-2-oxoquinoline-3,4- dicarbonitriles and 6,7-dimethoxy-2-oxoquinoline-3,4-dicarbonitriles

4-Chlorocarbostyrils 3, 12, 17, 24, 26 with methoxy substituents in 6, 7, or 6,7-position react with potassium cyanide in a p-toluenesulfinate mediated reaction either to the highly fluorescent and stable 2-oxoquinoline-3,4- dicarbonitriles 6, 27, 29, 30 or at slightly lower temperatures to 4-monocarbonitriles 5, 13, 18. 4-Chlorocarbostyril 3 and lithium p-toluenesulfinate gave pure 4-toluenesulfonylquinolone 4, which reacted with potassium cyanide either to monocarbonitrile 5 or dicarbonitrile 6, depending on the reaction conditions. 4-Trifluoromethylquinolones 9 and 19 were prepared for fluorescence comparison from the appropriate methoxyaniline and 4,4,4-trifluoroacetoacetate. The fluorescence properties such as emission wavelengths and quantum yields of 6-methoxyderivatives 4, 5, 6, 9, 13 were studied and compared with those of 7-methoxy derivatives 18, 19 and 6,7-dimethoxyderivatives 27, 28, 29, 30. 6,7-Dimethoxy derivatives show best results, showing long-waved fluorescence spectra up to 520 nm and acceptable quantum yields up to 0.46 for 3,4-dicyano derivative 27 excited at 440 nm in acetonitrile.

SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1

Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

4-Cyano-6,7-dimethoxycarbostyrils with solvent- and pH-independent high fluorescence quantum yields and emission maxima

Highly fluorescent and stable 6,7-dimethoxy-2-oxoquinoline-4-carbonitriles (11) were synthesized starting from appropriate 4-hydroxyquinolones 3 via reactive 4-chloroquinolones 8 by using toluenesulfinates as catalysts. In contrast to the well-described 4-trifluoromethyl-substituted analogues 18, N-substituted derivatives 11 fluoresce in water, polar, and apolar solvents in a narrow 430-440-nm window with almost constant quantum yield of 0.5. Equal excitation is possible in the broad double maximum between 385 and 410 nm yielding identical data between pH 1 and 11. These properties could lead to a broadly usable fluorescence standard. N-Alkylation with bromoacetate yields ester 13 in good yields. Reactive succinimidoyl (OSu) ester 15 was prepared by saponification to acid 14. With amino acids or peptides, linking to labeled derivatives 17 was achieved under mild conditions in slightly basic aqueous media. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

FUSED HETEROCYCLIC COMPOUNDS

This invention provides fused heterocyclic compounds, pharmaceutical compositions of the compounds, and methods of using the compounds for the treatment of, inter alia, IL-12 related disease and disorders.