1123172-99-5

Basic information

• Product Name: ((3R,4S,5S)-5-(3,5-difluoro-4-nitrobenzyl)-4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)carbamate
• Synonyms: ((3R,4S,5S)-5-(3,5-difluoro-4-nitrobenzyl)-4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)carbamate
• CAS NO: 1123172-99-5
• Molecular Weight: 404.435
• Mol File: 1123172-99-5.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: ((3R,4S,5S)-5-(3,5-difluoro-4-nitrobenzyl)-4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)carbamate(CAS DataBase Reference)
• NIST Chemistry Reference: ((3R,4S,5S)-5-(3,5-difluoro-4-nitrobenzyl)-4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)carbamate(1123172-99-5)
• EPA Substance Registry System: ((3R,4S,5S)-5-(3,5-difluoro-4-nitrobenzyl)-4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)carbamate(1123172-99-5)

Safety Data

• Hazardous Substances Data: 1123172-99-5(Hazardous Substances Data)

Upstream product

• 67567-26-4 4-bromo-2,6-difluoroaniline 
• 147808-42-2 5-bromo-1,3-difluoro-2-nitro-benzene 
• 1123172-90-6 5-(bromomethyl)-1,3-difluoro-2-nitro-benzene 
• 1123172-89-3 (3,5-difluoro-4-nitrophenyl)methanol 
• 1123172-87-1 methyl 3,5-difluoro-4-nitrobenzoate 

Downstream Products

• 1123173-42-1 {(3R,4S,5S)-5-[3-fluoro-4-nitro-5-(2,2,2-trifluoro-ethoxy)-benzyl]-4-hydroxy-tetrahydro-thiopyran-3-yl}-carbamic acid tert-butyl ester 
• 1123173-33-0 [(1S,3R,4S,5S)-5-(3,5-difluoro-4-nitro-benzyl)-4-hydroxy-1-oxo-tetrahydro-thiopyran-3-yl]-carbamic acid tert-butyl ester 
• 1123173-00-1 (3R,4S,5S)-3-((3-(tert-butyl)benzyl)-amino)-5-(3,5-difluoro-4-nitrobenzyl)-4-hydroxytetrahydro-2H-thiothiopyran 
• 1204343-82-7 (3R,4S,5S)-3-amino-5-(3,5-difluoro-4-nitrobenzyl)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide hydrochloride 
• 1204343-84-9 (3R,4S,5S)-3-((3-(tert-butyl)benzyl)amino)-5-(3,5-difluoro-4-nitro-benzyl)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide 
• 1367877-83-5 C₂₅H₃₃FN₂O₆S 
• 1123173-71-6 C₂₇H₃₇FN₂O₄S 
• 1204342-83-5 (3S,4S,5R)-3-(4-amino-3-fluoro-5-(oxetan-3-yloxy)benzyl)-5-((3-(tert-butyl)benzyl)amino)-4hydroxytetrahydro-2H-thiopyran 1,1-dioxide 
• 1368856-11-4 (3S,4S,5R)-3-(4-amino-3-fluoro-5-(2-fluoroethoxy)benzyl)-5-((3-(tert-butyl)benzyl)amino)-4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide dihydrochloride 
• 1204343-85-0 C₂₆H₃₅FN₂O₇S 

Relevant articles and documents

Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: Structure-based design and in vivo reduction of amyloid β-peptides

Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure-activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood-brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APP51/16 transgenic mice at oral doses of 180 μmol/kg demonstrated significant reduction of brain Aβ levels.