292632-98-5

Basic information

• Product Name: L-685 458
• Synonyms: (5S)-(tert-Butoxycarbonylamino)-6-phenyl-(4R)-hydroxy-(2R)-benzylhexanoyl)-L-leucy-L-phenylalaninamide;N-[(2R,4R,5S)-5-[[(1,1-DiMethylethoxy)carbonyl]aMino]-4-hydroxy-1-oxo-6- phenyl-2-(phenylMethyl)hexyl]-L-leucyl-L-phenylalaninaMide
• CAS NO: 292632-98-5
• Molecular Formula: C39H52N4O6
• Molecular Weight: 672.862
• Mol File: 292632-98-5.mol
• Article Data: 7

Chemical Properties

• Melting Point: 212-213 °C
• Boiling Point: 938.5±65.0 °C(Predicted)
• Appearance: white/solid
• Density: 1.155±0.06 g/cm3(Predicted)
• Storage Temp.: −20°C
• Solubility: DMSO: >10 mg/mL, soluble
• PKA: 12.09±0.46(Predicted)
• CAS DataBase Reference: L-685 458(CAS DataBase Reference)
• NIST Chemistry Reference: L-685 458(292632-98-5)
• EPA Substance Registry System: L-685 458(292632-98-5)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 292632-98-5(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 292632-98-5 differently. You can refer to the following data:
1. N-[(2R,4R,5S)-5-[[(1,1-Dimethylethoxy)carbonyl]amino]-4-hydroxy-1-oxo-6-phenyl-2-(phenylmethyl)hexyl]-L-leucyl-L-phenylalaninamide, is a γ-Secretase Inhibitor, the enzyme complex that catalyzes the cleavage of the amyloid precursor protein (APP) to generate amyloid β-peptide (Aβ), the major causative agent in Alzheimer disease (AD).
2. L-685,458 has been used to attenuate Notch signalling in ovary culture. It has also been used to analyze the specificity of the γ-secretase activity in brain tissue samples.

Biological Activity

Potent and selective γ -secretase inhibitor (IC 50 = 17 nM) that displays > 50-fold selectivity over a range of aspartyl, serine and cysteine proteases. Exhibits equal potency for inhibition of A β 40 and A β 42 peptides (IC 50 values are 48 and 67 nM respectively in human neuroblastoma cells). Also regulates CXCR4 and VEGFR2 expression through inhibition of Notch signaling in vitro .

Biochem/physiol Actions

L-685,458 mimics the transition state in aspartyl protease. It possesses an IC50 of 17nM with respect to inhibition of Aβ synthesis. It is known to block Notch (neurogenic locus notch homolog protein) signaling, which in turn reduces ERK (extracellular signal regulated kinase) phosphorylation by EGF (epidermal growth factor). L-685,458 targets the active site and substrate binding site of the enzyme.

Upstream product

• 292620-20-3 (1S,4R)-{1-benzyl-4-[1-(1S)-carbamoyl-(2-phenylethylcarbamoyl)-(1S)-3-methylbutylcarbamoyl]-2-oxo-5-phenylpentyl}carbamic acid tert-butyl ester 
• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 5241-58-7 L-Phenylalanine amide 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 88463-18-7 (S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionamide 
• 33900-15-1 (2S)-N-[(1S)-2-amino-1-benzyl-2-oxoethyl]-2-[(tert-butoxycarbonyl)amino]-4-methylpentanamide 
• 38678-60-3 leucylphenylalanylamide 
• 98818-41-8 (3R,5S)-3-benzyl-5-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-phenylethyl}dihydrofuran-2-(3H)-one 
• 98818-45-2 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-phenylmethylhexanoic acid 
• 98818-51-0 N-(1,1-dimethylethoxycarbonyl)-5(S)-amino-4(S)-(t-butyldimethylsilyloxy)-6-phenyl-2(R)-(phenylmethyl)hexanoic acid 
• 126409-24-3 {(1S)-benzyl-(4R)-[1-((1S)-carbamoyl-2-phenyl-ethylcarbamoyl)-(1S)-3-methyl-butyl-carbamoyl]-(2S)-hydroxy-5-phenyl-pentyl} carbamic acid tert-butyl ester 
• 126410-32-0 {(1S,2S,4R)-1-Benzyl-2-(tert-butyl-dimethyl-silanyloxy)-4-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-5-phenyl-pentyl}-carbamic acid tert-butyl ester 
• 63-91-2 L-phenylalanine 
• 565454-73-1 (1,4-dibenzyl-2-oxo-pent-4-enyl)-carbamic acid tert-butyl ester 

Downstream Products

• 98818-74-7 L-364,505 

Relevant articles and documents

Allyltrichlorostannane additions to α-amino aldehydes: Application to the total synthesis of the aspartyl protease inhibitors L-682,679, L-684,414, L-685,434, and L-685,458

The hydroxyethylene dipeptide isosteres L-682,679, L-684,414, L-685,434, and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-amino aldehyde, followed by hydroboration of the corresponding 1,2-

Short total synthesis of aspartyl protease inhibitors L-685,434, L-682,679 and L-685,458

Hydroxyethylene dipeptide isosteres L-685,434, L-682,679 and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-aminoaldehyde followed by hydroboration of the corresponding 1,2-syn and 1,2-anti a

HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: An investigation into the role of the P1' side chain on structure-activity

A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe-Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T- lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay.