1620576-86-4

Basic information

• Product Name: 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one
• Synonyms: 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one
• CAS NO: 1620576-86-4
• Molecular Formula: C27H39N9O4
• Molecular Weight: 553.65646
• Mol File: 1620576-86-4.mol
• Article Data: 4

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one(1620576-86-4)
• EPA Substance Registry System: 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one(1620576-86-4)

Safety Data

• Hazardous Substances Data: 1620576-86-4(Hazardous Substances Data)

Upstream product

• 1620576-81-9 5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazine-2-carbonitrile 
• 1620583-33-6 (Z)-5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazine-2-carbohydrazonamide 
• 1620576-82-0 tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate 
• 1639042-85-5 tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate 
• 91267-19-5 3-(tetrahydropyran-2-yloxy)-propionic acid methyl ester 
• 16298-03-6 Methyl 3-amino-2-pyrazinecarboxylate 
• 6761-52-0 3-amino-pyrazine-2-carbohydrazide 
• 1620576-77-3 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine 
• 1620576-78-4 5-bromo-3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine 
• 1620576-80-8 3-amino-6-bromo-N'-pivaloylpyrazine-2-carbohydrazide 
• 1225062-23-6 3-amino-6-bromopyrazine-2-carbohydrazide 
• 6966-01-4 methyl 3-amino-6-bromopyrazine-2-carboxylate 
• 1221443-23-7 3-[(2RS)-tetrahydro-2H-pyran-2-yloxy]propanoic acid 
• 1620576-85-3 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-ethyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine 

Downstream Products

• 1620576-64-8 AZD-8835 

Relevant articles and documents

Discovery of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (AZD8835): A potent and selective inhibitor of PI3Kα and PI3Kδ for the treatment of cancers

Starting from potent inhibitors of PI3Kα having poor general kinase selectivity (e.g., 1 and 2), optimisation of this series led to the identification of 25, a potent inhibitor of PI3Kα (wild type, E545K and H1047R mutations) and PI3Kδ, selective versus PI3Kβ and PI3Kγ, with excellent general kinase selectivity. Compound 25 displayed low metabolic turnover and suitable physical properties for oral administration. In vivo, compound 25 showed pharmacodynamic modulation of AKT phosphorylation and near complete inhibition of tumour growth (93% tumour growth inhibition) in a murine H1047R PI3Kα mutated SKOV-3 xenograft tumour model after chronic oral administration at 25 mg/kg b.i.d. Compound 25, also known as AZD8835, is currently in phase I clinical trials.

CHEMICAL COMPOUNDS

The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1 to R5 have any of the meanings defined hereinbefore in the description: processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.