1296272-02-0

Basic information

• Product Name: 8-(1-(R)-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide
• Synonyms: 8-(1-(R)-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide
• CAS NO: 1296272-02-0
• Molecular Weight: 471.504
• Mol File: 1296272-02-0.mol

Chemical Properties

• CAS DataBase Reference: 8-(1-(R)-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: 8-(1-(R)-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide(1296272-02-0)
• EPA Substance Registry System: 8-(1-(R)-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide(1296272-02-0)

Safety Data

• Hazardous Substances Data: 1296272-02-0(Hazardous Substances Data)

Upstream product

• 71407-98-2 3-acetyl-5-bromo-4-hydroxybenzoic acid 
• 99-76-3 methyl 4-hydroxylbenzoate 
• 57009-12-8 methyl 3-acetyl-4-hydroxybenzoate 
• 1296271-71-0 methyl 8-(1-hydroxyethyl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate 
• 1296271-69-6 methyl 8-acetyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate 
• 1296271-68-5 methyl 8-bromo-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate 
• 29415-97-2 methyl 3-bromo-4-hydroxybenzoate 
• 1296271-73-2 8-(1-hydroxyethyl)-N,N-dimethyl-2-[(2R)-2-methylmorpholin-4-yl]-4-oxo-4H-chromene-6-carboxamide 
• 1296271-66-3 methyl 8-bromo-2-(ethylthio)-4-oxo-4H-chromene-6-carboxylate 
• 1296271-65-2 methyl 8-bromo-4-hydroxy-2-thioxo-2H-chromene-6-carboxylate 
• 160753-84-4 methyl 3-acetyl-5-bromo-4-hydroxybenzoate 
• 1296271-72-1 8-(1-hydroxyethyl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid 
• 1296271-74-3 8-(1-bromoethyl)-N,N-dimethyl-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide hydrobromide 
• 372-39-4 3,5-difluoroaniline 

Relevant articles and documents

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 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.