1067648-50-3

Upstream product

• 1067648-43-4 5-azido-2,3,5-trideoxy-6-O-(3,5-difluorobenzyl)-2-methyl-L-idono-1,4-lactone 
• 140-75-0 para-fluorobenzylamine 
• 1067648-38-7 imidazole-1-carbothioic acid O-(5-(1,2-bisbenzyloxyethyl)-2-methoxytetrahydrofuran-3-yl) ester 
• 1079398-63-2 methyl 5,6-di-O-benzyl-3-deoxy-D-glucofuranoside 
• 1067648-40-1 5,6-di-O-benzyl-2,3-dideoxy-2-methyl-D-glucono-1,4-lactone 
• 1056674-35-1 5,6-di-O-benzyl-2,3-dideoxy-D-glucono-1,4-lactone 
• 1067648-42-3 2,3-dideoxy-6-O-(3,5-difluorobenzyl)-2-methyl-D-glucono-1,4-lactone 
• 1067648-39-8 methyl 5,6-di-O-benzyl-2,3-dideoxy-D-glucofuranoside 
• 1067648-41-2 2,3-dideoxy-2-methyl-D-glucono-1,4-lactone 

Downstream Products

• 1067648-51-4 (2R,4S,5S)-5-amino-6-(3,5-difluorobenzyloxy)-4-hydroxy-2-methylhexanoic acid 4-fluorobenzylamide 

Relevant academic research and scientific papers

Synthesis of potent BACE-1 inhibitors incorporating a hydroxyethylene isostere as central core

We herein describe the design and synthesis of a series of BACE-1 inhibitors incorporating a P1-substituted hydroxylethylene transition state isostere. The synthetic route starting from commercially available carbohydrates yielded a pivotal lactone intermediate with excellent stereochemical control which subsequently could be diversified at the P1-position. The final inhibitors were optimized using three different amines to provide the residues in the P2′-P3′ position and three different acids affording the residues in the P2-P3 position. In addition we report on the stereochemical preference of the P1′-methyl substituent in the synthesized inhibitors. All inhibitors were evaluated in an in vitro BACE-1 assay where the most potent inhibitor, 34-(R), exhibited a BACE-1 IC50 value of 3.1 nM.

AMIDE DERIVATIVES AS INHIBITORS OF ASPARTYL PROTEASES

The invention provides compounds of the formula (I). N-oxides, addition salts, quaternary amines, metal complexes, stereochemically isomeric forms and metabolites thereof, wherein W is H, C1-C6alkyl, C3-C6cycloalkyl, aryl or heterocyclyl; Q is aryl or heterocyclyl; A is a five or six membered saturated, partially unsaturated or aromatic ring; D is formula (II) or formula (III); and the other variables are as defined in the specification. The compounds of the invention are inhibitors of aspartyl proteases such as renin and BACE and are among other things useful for the treatment and/or prophylaxis of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency and for the treatment and or prophylaxis of conditions associated with BACE activity such as of Alzheimer's disease.