57663-05-5

Upstream product

• 15908-50-6 3-[di(methylthio)methylene]pentane-2,4-dione 
• 17649-86-4 4,4-bis(methylthio)but-3-en-2-one 
• 107-91-5 cyanoacetic acid amide 
• 17823-69-7 2-cyano-3,3-bis(methylthio)acrylamide 
• 67-64-1 acetone 
• 5147-80-8 [Bis(methylthio)methylene]malononitrile 

Downstream Products

• 1224854-91-4 C₁₃H₁₂N₄O 

Relevant academic research and scientific papers

EZH2 covalent irreversible inhibitor as well as preparation method and application thereof

The invention discloses an EZH2 covalent irreversible inhibitor as well as a preparation method and application thereof. The EZH2 covalent irreversible inhibitor comprises a compound with a structure as shown in a formula (I) or a formula (II) or a salt t

Design, Synthesis, and Pharmacological Evaluation of Second Generation EZH2 Inhibitors with Long Residence Time

Histone methyltransferase EZH2, which is the catalytic subunit of the PRC2 complex, catalyzes the methylation of histone H3K27 - a transcriptionally repressive post-translational modification (PTM). EZH2 is commonly mutated in hematologic malignancies and frequently overexpressed in solid tumors, where its expression level often correlates with poor prognosis. First generation EZH2 inhibitors are beginning to show clinical benefit, and we believe that a second generation EZH2 inhibitor could further build upon this foundation to fully realize the therapeutic potential of EZH2 inhibition. During our medicinal chemistry campaign, we identified 4-thiomethyl pyridone as a key modification that led to significantly increased potency and prolonged residence time. Leveraging this finding, we optimized a series of EZH2 inhibitors, with enhanced antitumor activity and improved physiochemical properties, which have the potential to expand the clinical use of EZH2 inhibition.

MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF

Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with methyl modifying enzymes. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with methyl modifying enzymes.

MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF

Provided are novel compounds of Formula (I): Formula (I); and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with methyl modifying enzymes. Also provided are pharmaceutic

MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF

Provided are compounds of Formula (I): and pharmaceutically acceptable salts and compositons thereof, which are useful for treating a variety of conditions associated with methyl modifying enzymes.

Synthesis and reactivity of 3-amino-1H-pyrazolo[4,3-c]pyridin-4(5H)-ones: development of a novel kinase-focussed library

3-Amino-1H-pyrazolo[4,3-c]pyridin-4(5H)-ones represent a potentially attractive heteroaromatic scaffold for drug-discovery chemistry. In particular, the arrangement of hydrogen bond donor and acceptor groups in the bicyclic core can fulfil the requirement

α,α-Dioxoketene Dithioacetals as Starting Materials for the Synthesis of Polysubstituted Pyridines

Reactions of 3-acetyl-4,4-bis(methylthio)but-3-en-2-one 2e and methyl 2-acetyl-3,3-bis(methylthio)prop-2-enoate 2f with cyanothioacetamide, cyanoacetamide, or 2-amino-1,3,3-tricyanoprop-1-ene and base, followed by treatment with acid give polysubstituted pyridines such as 8, 10, 11, 13, 15 and 16.Further elaboration of these products leads to bicyclic systems such as thienopyridines 17 and 18 and pyrazolopyridine 21 and then to tricyclic systems including pyrazolothienopyridine 19 and dipyrazolopyridine 22.

Synthesis of 4-Methylthio-2(1H)-pyridone Derivatives Using Ketene Dithioacetals

Reaction of various active methylene compounds with ketene dithioacetals, bis(methylthio)methylenemalononitrile (1a) and bis(methylthio)methylenecyanoacetamide (1b) gave the corresponding 3-cyano-4-methylthio-2(1H)-pyridone derivatives.The transformation