67643-17-8

Usage

Uses

Used in Pharmaceutical Synthesis:
4-Hydroxy-6-Methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile is used as an intermediate in the synthesis of pharmaceuticals. Its structural features make it a valuable component in the development of new drugs, particularly those targeting cardiovascular diseases, as dihydropyridines are known for their calcium channel-blocking properties.
Used in Agrochemical Production:
In the agrochemical industry, 4-Hydroxy-6-Methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile is utilized as an intermediate for the synthesis of various agrochemicals. Its reactivity and functional groups allow for the creation of compounds that can be used in pest control and crop protection.
Used in Medicinal Chemistry Research:
4-Hydroxy-6-Methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile is also used in medicinal chemistry for research purposes. Its unique structure and reactivity make it a promising candidate for the development of novel therapeutic agents, particularly in the areas of cardiovascular and neurological treatments.
Used in Organic Compounds Synthesis:
4-Hydroxy-6-Methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile is utilized as an intermediate in the synthesis of other organic compounds. Its versatility in chemical reactions allows for the creation of a wide range of products, from specialty chemicals to advanced materials.

Upstream product

• 67643-16-7 2-amino-6-methyl-4-oxo-4H-pyran-3-carbonitrile 
• 15456-25-4 3-methylenecyclobutanone 
• 674-82-8 4-methyleneoxetan-2-one 
• 109-77-3 malononitrile 

Downstream Products

• 38367-36-1 2,4-dichloro-6-methyl-3-pyridinecarbonitrile 
• 582300-58-1 4-chloro-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile 
• 582300-58-1 4-chloro-2-hydroxy-6-methylnicotinonitrile 
• 1354528-16-7 2-hydroxy-4-methoxy-6-methylnicotinonitrile 
• 1438382-15-0 3-(aminomethyl)-4-methoxy-6-methylpyridin-2-ol 
• 1621862-70-1 CPI-1205 

Relevant academic research and scientific papers

1,5,7-TRISUBSTITUTED ISOQUINOLINE DERIVATIVES, PREPARATION THEREOF, AND USE THEREOF IN MEDICINES

The present disclosure relates to 1,5,7-trisubstituted isoquinoline derivatives, their preparation and pharmaceutical use. In particular, the present disclosure discloses a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and a preparation method and use thereof. The definitions of the groups in the formula can be found in the specification and claims.

Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

Zeste enhancer homolog 2 (EZH2) is highly expressed in various malignant tumors, which could silence tumor suppressor genes via trimethylation of H3K27. Herein was first reported a novel series of pyrrole-3-carboxamide derivatives carrying a pyridone fragment as EZH2 inhibitors. By combining computational modeling, in vitro cellular assays and further rational structure-activity relationship exploration and optimization, compound DM-01 showed powerful inhibition towards EZH2. DM-01 was found to have significant ability to reduce the cellular H3K27me3 level in K562 cells in the Western blot test. Meanwhile, our data showed that knockdown EZH2 in A549 cells resulted in a decrease of cell sensitivity to DM-01 at 50 and 100 μM. DM-01 could also increase the transcription expression of DIRAS3 in a dose-dependent manner, a tumor suppressor in the downstream of EZH2, suggesting it was worth investigating further as a lead compound.

5-Hydroxyindole-based EZH2 inhibitors assembled via TCCA-catalyzed condensation and Nenitzescu reactions

5-Hydroxyindole derivatives have various demonstrated biological activities. Herein, we used 5-hydroxyindole as a synthetic starting point for structural alterations in a combinatorial process to synthesize 22 different compounds with EZH2 inhibitor pharmacophores. A series of 5-hydroxyindole-derived compounds were screened inhibitory activities against K562 cells. According to molecular modeling and in vitro biological activity assays, the preliminary structure-activity relationship was summarized. Compound L–04 improved both the H3K27Me3 reduction and antiproliferation parameters (IC50 = 52.6 μM). These findings revealed that compound L–04 is worthy of consideration as a lead compound to design more potent EZH2 inhibitors. During the preparation of compounds, we discovered that trichloroisocyanuric acid (TCCA) is a novel catalyst which demonstrates condensation-promoting effects. To gain insight into the reaction, in situ React IR technology was used to confirm the reactivity. Different amines were condensed in high yields with β-diketones or β-ketoesters in the presence of TCCA to afford the corresponding products in a short time (10~20 min), which displayed some advantages and provided an alternative condensation strategy.

4,5,6-TRI-SUBSTITUTED INDAZOLES DERIVATIVES, PREPARATION THEREOF, AND USE THEREOF IN MEDICINES

Provided are 4,5,6-tri-substituted indazoles derivatives, a preparation method therefor, and a use thereof in medicines. Specifically, provided are compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates, or prodrugs thereof

SULFONYL-SUBSTITUTED BENZOHETEROCYCLIC DERIVATIVE, PREPARATION METHOD AND MEDICAL USE THEREOF

The present invention relates to a sulfonyl-substituted benzoheterocyclic derivative, a preparation method and medical use thereof. Particularly, disclosed is a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate, or prodrug thereof, and a preparation method and application thereof. The definition of each group in the formula can be found in the specification and the claims.

INHIBITORS OF EZH2

The present invention relates to compounds that inhibit activity of the histone lysine methyltransferase, Enhancer of Zeste Homolog 2 (EZH2), pharmaceutical compositions comprising the compounds, and methods of using the compounds to treat cancer, such as hematologic and solid tumors.

IMIDAZOPYRIDINE EZH2 INHIBITORS

The present invention relates to imidazopyridines of general formula (I), to a method for their preparation, to intermediates for their preparation, to pharmaceutical compositions comprising at least one of those compounds, and to the use thereof.

Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitabl

Polycomb repressive complex 2 (PRC2) has been shown to play a major role in transcriptional silencing in part by installing methylation marks on lysine 27 of histone 3. Dysregulation of PRC2 function correlates with certain malignancies and poor prognosis

INDOLE DERIVATIVES AS MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF

Agents of formulas (l)/(ll)/(lll) for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.

Discovery, design, and synthesis of indole-based EZH2 inhibitors

The discovery and optimization of a series of small molecule EZH2 inhibitors is described. Starting from dimethylpyridone HTS hit (2), a series of indole-based EZH2 inhibitors were identified. Biochemical potency and microsomal stability were optimized during these studies and afforded compound 22. This compound demonstrates nanomolar levels of biochemical potency (IC50 = 0.002 μM), cellular potency (EC50 = 0.080 μM), and afforded tumor regression when dosed (200 mpk SC BID) in an EZH2 dependent tumor xenograft model.