1443035-43-5

Basic information

• Product Name: (5R)-5-(5-bromo-2-fluorophenyl)-6-(difluoromethylene)-5-methylmorpholin-3-thione
• Synonyms: (5R)-5-(5-bromo-2-fluorophenyl)-6-(difluoromethylene)-5-methylmorpholin-3-thione
• CAS NO: 1443035-43-5
• Molecular Weight: 352.175
• Mol File: 1443035-43-5.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: (5R)-5-(5-bromo-2-fluorophenyl)-6-(difluoromethylene)-5-methylmorpholin-3-thione(CAS DataBase Reference)
• NIST Chemistry Reference: (5R)-5-(5-bromo-2-fluorophenyl)-6-(difluoromethylene)-5-methylmorpholin-3-thione(1443035-43-5)
• EPA Substance Registry System: (5R)-5-(5-bromo-2-fluorophenyl)-6-(difluoromethylene)-5-methylmorpholin-3-thione(1443035-43-5)

Safety Data

• Hazardous Substances Data: 1443035-43-5(Hazardous Substances Data)

Upstream product

• 1443035-41-3 (5R)-5-(5-bromo-2-fluorophenyl)-6-(difluoromethylene)-5-methylmorpholin-3-one 
• 1443035-39-9 (5R)-5-(5-bromo-2-fluorophenyl)-6-chloro-5-methyl-6-(trifluoromethyl)morpholin-3-one 
• 1443035-37-7 C₁₂H₁₀BrF₄NO₃ 
• 1443035-35-5 (3R)-3-(5-bromo-2-fluorophenyl)-3-methylmorpholine-2,5-dione 
• 1443035-33-3 C₁₁H₉BrClFNO₃^(1-)*Na⁽¹⁺⁾ 
• 1443035-31-1 C₉H₈BrFNO₂^(1-)*Na⁽¹⁺⁾ 
• 1213855-88-9 (R)-2-amino-2-(5-bromo-2-fluoro-phenyl)-propionic acid methyl ester 
• 1266784-23-9 (RS)-2-amino-2-(5-bromo-2-fluoro-phenyl)-propionic acid 
• 1350523-51-1 rac-2-amino-2-(5-bromo-2-fluoro-phenyl)-propionitrile 
• 198477-89-3 1-(5-bromo-2-fluorophenyl)ethan-1-one 

Downstream Products

• 1443035-83-3 C₁₆H₁₃F₃N₄O 
• 1443035-49-1 N-{3-(3R)-(5-amino-2-(difluoromethylene)-3-methyl-3,6-dihydro-2H-1,4-oxazin-3-yl)-4-fluorophenyl}-5-methoxypyrazine-2-carboxamide 
• 1443035-47-9 (5R)-5-(5-amino-2-fluorophenyl)-6-(difluoromethylene)-5-methyl-5,6-dihydro-2H-1,4-oxazin-3-amine 
• 1443035-45-7 (5R)-5-(5-bromo-2-fluorophenyl)-6-(difluoromethylene)-5-methyl-5,6-dihydro-2H-1,4-oxazin-3-amine 

Relevant articles and documents

Optimization of 1,4-Oxazine β-Secretase 1 (BACE1) Inhibitors Toward a Clinical Candidate

In previous studies, the introduction of electron withdrawing groups to 1,4-oxazine BACE1 inhibitors reduced the pKa of the amidine group, resulting in compound 2 that showed excellent in vivo efficacy, lowering Aβ levels in brain and CSF. However, a suboptimal cardiovascular safety margin, based on QTc prolongation, prevented further progression. Further optimization resulted in the replacement of the 2-fluoro substituent by a CF3-group, which reduced hERG inhibition. This has led to compound 3, with an improved cardiovascular safety margin and sufficiently safe in GLP toxicity studies to progress into clinical trials.

5-(3-AMINOPHENYL)-5-ALKYL-5,6-DIHYDRO-2H-[1,4]OXAZIN-3-AMINE DERIVATIVES

The present invention relates to novel 5-(3-aminophenyl)-5-alkyl-5,6-dihydro- 2H-[1,4]oxazin-3-amine derivatives as inhibitors of beta-secretase, also known as beta- site amyloid cleaving enzyme, BACE, BACE 1, Asp2, or memapsin2. The invention is also dir