17649-86-4

Upstream product

• 54893-95-7 ethyl 2-acetyl-3,3-bis(methylthio)acrylate 
• 5780-61-0 4,4-dichlorobut-3-en-2-one 
• 14527-26-5 2-methylisothiourea sulphate 
• 5188-07-8 sodium thiomethoxide 
• 75-15-0 carbon disulfide 
• 67-64-1 acetone 
• 74-88-4 methyl iodide 
• 624-92-0 Dimethyldisulphide 
• 560095-47-8 (3-buten-2-yl)pentamethyl phosphoric triamide 
• 15908-50-6 3-[di(methylthio)methylene]pentane-2,4-dione 
• 865-47-4 potassium tert-butylate 
• 75-05-8 acetonitrile 
• 123-54-6 acetylacetone 

Downstream Products

• 92807-28-8 5,5-Bis-methylmercapto-1-(4-methoxy-phenyl)-pentadien-1,4-on-3 
• 137612-33-0 (4E,6E)-7-(4-Methoxy-phenyl)-1,1-bis-methylsulfanyl-hepta-1,4,6-trien-3-one 
• 117671-78-0 (Z)-1-(4-Chloro-phenyl)-3-hydroxy-5,5-bis-methylsulfanyl-penta-2,4-dien-1-one 
• 132059-06-4 3-benzylideneamino-6-methyl-4-(methylthio)-pyran-2-one 
• 117671-82-6 (Z)-3-Hydroxy-1-(3-methoxy-phenyl)-5,5-bis-methylsulfanyl-penta-2,4-dien-1-one 
• 117671-79-1 (Z)-3-Hydroxy-1-(4-methoxy-phenyl)-5,5-bis-methylsulfanyl-penta-2,4-dien-1-one 
• 128039-37-2 2,5-bis(methylthio)-7-methyl-3-phenylpyrazolo<1,5-a>pyrimidine 
• 62453-10-5 (Z)-4-methylsulfanyl-3-penten-2-one 
• 86310-01-2 (E)-4-methylsulfanyl-3-penten-2-one 
• 117671-88-2 2,6-Bis(methylthio)-4-hydroxyacetophenone 
• 33944-94-4 β-(methylthiomethylene)acetone 
• 96899-26-2 (Z)-5,5-dimethyl-4-methylthiohex-3-en-2-one 
• 99878-36-1 2-Methylsulfanyl-6-p-tolylamino-thiopyran-4-one 
• 85814-61-5 1-(2,5-diphenyl-1H-pyrrol-3-yl)ethanone 

Relevant academic research and scientific papers

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.

Remote C-H Activation Strategy Enables Total Syntheses of Nortriterpenoids (±)-Walsucochin B and (±)-Walsucochinoids M and N

Total syntheses of (±)-walsucochin B and (±)-walsucochinoids M and N have been achieved from farnesyl bromide. The key steps of the synthetic sequence are the titanocene-mediated radical cyclization and base-induced cycloaromatization for the rapid construction of the 6/6/5/6-fused tetracyclic skeleton. Importantly, a Cu-mediated remote C-H hydroxylation reaction has been developed to site-selectively install the oxygen function at the C-7 position of the target molecules, thus solving the biggest challenge for the synthesis of the compounds.

Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies

Phenotypic screening of a Medicines for Malaria Venture compound library against Mycobacterium tuberculosis (Mtb) identified a cluster of pan-active 2-pyrazolylpyrimidinones. The biology triage of these actives using various tool strains of Mtb suggested a novel mechanism of action. The compounds were bactericidal against replicating Mtb and retained potency against clinical isolates of Mtb. Although selected MmpL3 mutant strains of Mtb showed resistance to these compounds, there was no shift in the minimum inhibitory concentration (MIC) against a mmpL3 hypomorph, suggesting mutations in MmpL3 as a possible resistance mechanism for the compounds but not necessarily as the target. RNA transcriptional profiling and the checkerboard board 2D-MIC assay in the presence of varying concentrations of ferrous salt indicated perturbation of the Fe-homeostasis by the compounds. Structure-activity relationship studies identified potent compounds with good physicochemical properties and in vitro microsomal metabolic stability with moderate selectivity over cytotoxicity against mammalian cell lines.

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

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.

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

Alternative Palladium-Catalyzed Vinylic C?H Difluoroalkylation of Ketene Dithioacetals Using Bromodifluoroacetate Derivatives

A palladium-catalyzed cross-coupling of α-oxo ketene dithioacetals and bromodifluoroacetate derivatives has been developed for the synthesis of a class of CF2-containing tetra-substituted olefins, which has potential to extend to drug design an

PYRAZOLO[1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS

The invention provides substituted pyrazolo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidinyl carboxamide compounds described herein include 2-heterocyclyl-4-alkyl-pyrazolo[1,5-a]pyrirnidine-3-carboxarnide compounds and variants thereof.

Experimental and Theoretical Investigations of the Bromination of Phenols with β and γ Aliphatic Substituents, including Rings

Bromination reactions of substituted and ring fused phenols were studied by both experiment (t-BuNH-Br) and computation (density functional theory). The outcomes support each other, indicating a clear and predictable regioselective preference among 3,4-bis-alkylated and 3,4-ring-fused phenols.