160753-84-4

Upstream product

• 57009-12-8 methyl 3-acetyl-4-hydroxybenzoate 
• 16357-40-7 3-acetyl-4-hydroxybenzoic acid 
• 149817-68-5 methyl 4-acetoxy-3-bromobenzoate 
• 67-56-1 methanol 
• 71407-98-2 3-acetyl-5-bromo-4-hydroxybenzoic acid 
• 29415-97-2 methyl 3-bromo-4-hydroxybenzoate 
• 99-76-3 methyl 4-hydroxylbenzoate 

Downstream Products

• 198477-87-1 methyl 3-acetyl-5-bromo-4-methoxybenzoate 
• 1296271-38-9 methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate 
• 1296270-25-1 N-(2-(dimethylamino)ethyl)-8-(1-(4-fluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide 
• 1296270-29-5 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-N-(2-(dimethylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide 
• 1296270-38-6 N-(2-(dimethylamino)ethyl)-8-(1-((4-fluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide 
• 1296271-95-8 8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide 
• 1296270-48-8 8-(1-(3-chlorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide 
• 1296272-00-8 8-{1-[(3,5-difluorophenyl)(methyl)amino]ethyl}-N,N-dimethyl-2-(morpholin-4-yl)-4-oxo-4H-chromene-6-carboxamide 
• 1296271-19-6 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-6-(4-hydroxypiperidine-1-carbonyl)-2-morpholino-4H-chromen-4-one 
• 1296271-15-2 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-N-(2-hydroxyethyl)-N-methyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide 
• 1296271-32-3 8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide 
• 1296271-43-6 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid 
• 1296271-42-5 methyl 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate 
• 1296271-51-6 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid 

Relevant academic research and scientific papers

Benzo[d]Isoxazole compound, preparation method and applications thereof

The invention provides a benzo[d]isoxazole compound, a preparation method and applications thereof, wherein the benzo[d]isoxazole compound has novel structure, can be used as a BET bromodomain receptor inhibitor, and can effectively inhibit the bromodomai

Structure-Based Discovery and Optimization of Benzo [d] isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC)

The bromodomain and extra-terminal (BET) family proteins have gained increasing interest as drug targets for treatment of castration-resistant prostate cancer (CRPC). Here, we describe the design, optimization, and evaluation of benzo[d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal structures of the representative inhibitors in complex with BRD4(1) provided solid structural basis for compound optimization. The two most potent compounds, 6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of 82 and 81 nM, respectively. They also exhibited high selectivity over other non-BET subfamily members. The compounds potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. These potent and selective BET inhibitors represent a new class of compounds for the development of potential therapeutics against CRPC.

Discovery of (R)-8-(1-(3,5-difluorophenylamino)ethyl)- N, N -dimethyl-2-morpholino-4-oxo-4 H -chromene-6-carboxamide (AZD8186): A potent and selective inhibitor of PI3Kβ and PI3Kδ for the treatment of PTEN-deficient cancers

Several studies have highlighted the dependency of PTEN deficient tumors to PI3Kβ activity and specific inhibition of PI3Kδ has been shown activity against human B-cell cancers. We describe the discovery and optimization of a series of 8-(1-anilino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamides as PI3Kβ/δ inhibitors, which led to the discovery of the clinical candidate 13, also known as AZD8186. On the basis of the lower lipophilicity of the chromen-4-one core compared to the previously utilized pyrido[1,2-a]pyrimid-4-one core, this series of compounds displayed high metabolic stability and suitable physical properties for oral administration. Compound 13 showed profound pharmacodynamic modulation of p-Akt in PTEN-deficient PC3 prostate tumor bearing mice after oral administration and showed complete inhibition of tumor growth in the mouse PTEN-deficient PC3 prostate tumor xenograft model. 13 was selected as a clinical candidate for treatment of PTEN-deficient cancers and has recently entered phase I clinical trials.

CHROMENONE COMPOUNDS AS PI 3 -KINASE INHIBITORS FOR THE TREATMENT OF CANCER

The invention concerns chromenone compounds of Formula I; or pharmaceutically-acceptable salts thereof, wherein each of R1, R2, R3, R4, R5, n and R6 has any of the meanings defined hereinbe

CHROMENONE DERIVATIVES

The invention concerns chromenone compounds of Formula I; or pharmaceutically-acceptable salts thereof, wherein each of R1, R2, R3, R4, R5, n and R6 has any of the meanings defined hereinbe

CHROMENONE DERIVATIVES WITH ANTI-TUMOUR ACTIVITY

The invention concerns chromenone derivatives of Formula (I) or a pharmaceutically-acceptable salts thereof, wherein each of R1, R2, R3, R4, R5, R6, R7, R8, n and R9 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.

CHROMENONE DERIVATIVES

The invention concerns chromenone derivatives of Formula I or a pharmaceutically-acceptable salts thereof, wherein each of R1, R2, R3, R4, R5, R6, R7, R8, n and R9 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.