1044870-92-9

Upstream product

• 861856-50-0 (4-formyl-2,6-dimethyl-phenoxy)-acetic acid 
• 63920-73-0 2-amino-4,6-dimethoxybenzamide 
• 241498-49-7 2-(4-formyl-2,6-dimethylphenoxy)acetic acid methyl ester 
• 21544-81-0 4,6-dimethoxyindoline-2,3-dione 
• 40891-33-6 3,5-dimethoxyaniline hydrochloride 
• 10272-07-8 3.5-dimethoxyaniline 
• 21577-57-1 2-amino-4,6-dimethoxybenzoic acid 
• 2233-18-3 4-hydroxy-3,5-dimethylbenzaldehyde 
• 1044870-39-4 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxy-3,4-dihydroquinazoline-4-one 

Downstream Products

• 1253732-61-4 2-[4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy]-N-(4-methoxyphenyl)acetamide 
• 1253732-62-5 N-benzyl-2-[4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy]acetamide 
• 1253732-60-3 2-[4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy]-N-methylacetamide 
• 1044871-58-0 propylcarbamic acid-2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl ester 

Relevant academic research and scientific papers

Discovery of Novel Dual-Target Inhibitor of Bromodomain-Containing Protein 4/Casein Kinase 2 Inducing Apoptosis and Autophagy-Associated Cell Death for Triple-Negative Breast Cancer Therapy

Bromodomain-containing protein 4 (BRD4) is an attractive epigenetic target in human cancers. Inhibiting the phosphorylation of BRD4 by casein kinase 2 (CK2) is a potential strategy to overcome drug resistance in cancer therapy. The present study describes the synthesis of multiple BRD4–CK2 dual inhibitors based on rational drug design, structure–activity relationship, and in vitro and in vivo evaluations, and 44e was identified to possess potent and balanced activities against BRD4 (IC50 = 180 nM) and CK2 (IC50 = 230 nM). In vitro experiments show that 44e could inhibit the proliferation and induce apoptosis and autophagy-associated cell death of MDA-MB-231 and MDA-MB-468 cells. In two in vivo xenograft mouse models, 44e displays potent anticancer activity without obvious toxicities. Taken together, we successfully synthesized the first highly effective BRD4–CK2 dual inhibitor, which is expected to be an attractive therapeutic strategy for triple-negative breast cancer (TNBC).

TREATMENT OF DISEASES BY EPIGENETIC REGULATION

The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of diseases or disorders that are susceptible to administration of a BET inhibitor.

In vitro biosynthesis, isolation, and identification of predominant metabolites of 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7- dimethoxyquinazolin-4(3H)-one (RVX-208)

The structures of the two predominant metabolites (M4 and M5) of RVX-208, observed both in in vitro human and animal liver microsomal incubations, as well as in plasma from animal in vivo studies, were determined. A panel of biocatalytic systems was tested to identify biocatalysts suitable for milligram scale production of metabolite M4 from RVX-208. Rabbit liver S9 fraction was selected as the most suitable system, primarily based on pragmatic metrics such as catalyst cost and estimated yield of M4 (～55%). Glucuronidation of RVX-208 catalyzed by rabbit liver S9 fraction was optimized to produce M4 in amounts sufficient for structural characterization. Structural studies using LC/MS/MS analysis and 1H NMR spectroscopy showed the formation of a glycosidic bond between the primary hydroxyl group of RVX-208 and glucuronic acid. NMR results suggested that the glycosidic bond has the β-anomeric configuration. A synthetic sample of M4 confirmed the proposed structure. Metabolite M5, hypothesized to be the carboxylate of RVX-208, was prepared using human liver microsomes, purified by HPLC, and characterized by LC/MS/MS and 1H NMR. The structure was confirmed by comparison to a synthetic sample. Both samples confirmed M5 as a product of oxidation of primary hydroxyl group of RVX-208 to carboxylic acid.

TREATMENT OF DISEASES BY EPIGENETIC REGULATION

The present disclosure provides non-naturally occurring polyphenol compounds that inhibit the bromodomain and extra terminal domain (BET) proteins. The disclosed compositions and methods can be used for treatment and prevention of cancer, including NUT midline carcinoma, Burkitt's Lymphoma, Acute Myelogenous Leukemia, and Multiple Myeloma; autoimmune or inflammatory diseases or conditions, and sepsis.

NOVEL ANTI-INFLAMMATORY AGENTS

Disclosed are methods of regulating interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1) and methods of treating and/or preventing cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s) by administering a naturally occurring or synthetic quinazolone derivative. The invention provides novel synthetic quinazolone compounds, as well as pharmaceutical compositions comprising those compounds.

COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES

The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.