184357-17-3

Basic information

• Product Name: 1,1-dimethylethyl [(1S,2R)-3-[(cyclohexylmethyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamate
• CAS NO: 184357-17-3
• Molecular Weight: 376.539
• Mol File: 184357-17-3.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: 1,1-dimethylethyl [(1S,2R)-3-[(cyclohexylmethyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamate(CAS DataBase Reference)
• NIST Chemistry Reference: 1,1-dimethylethyl [(1S,2R)-3-[(cyclohexylmethyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamate(184357-17-3)
• EPA Substance Registry System: 1,1-dimethylethyl [(1S,2R)-3-[(cyclohexylmethyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-carbamate(184357-17-3)

Safety Data

• Hazardous Substances Data: 184357-17-3(Hazardous Substances Data)

Upstream product

• 98760-08-8 (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 3218-02-8 cyclohexylmethylamine 
• 103127-52-2 ((S)-1-benzylallyl)carbamic acid tert-butyl ester 

Relevant articles and documents

Unnatural amino acid-substituted (hydroxyethyl)urea peptidomimetics inhibit γ-secretase and promote the neuronal differentiation of neuroblastoma cells

γ-Secretase, exhibiting characteristics of aspartyl protease, mediates the intramembranous proteolysis of β-amyloid precursor protein (APP) and Notch, and it is considered to be a prime pharmacological target in the development of therapeutics for Alzheimer's disease (AD). To identify compounds that block γ-secretase-mediated proteolysis, we used a highly sensitive cell-based reporter gene assay for γ-secretase in which Gal4/VP16-tagged C99-APP was expressed as the immediate substrate of γ-secretase, and Gal4/VP16-tagged APP intracellular domain released by the γ-secretase cleavage then activated the expression of the Gal4-driven luciferase reporter gene. Using this reporter assay, we demonstrated that the newly synthesized (hydroxyethyl)urea peptidomimetics, which contain unnatural amino acid moieties at positions P1′ and/or P3′, can effectively inhibit γ-secretase activity and significantly reduce Aβ production. The γ-secretase-dependent S3 cleavage of Notch was also consistently blocked by these (hydroxyethyl) ureas as evidenced by the decreased generation of the Notch intracellular domain, a prerequisite for the activation of Notch signaling. The inhibition of Notch signaling by active Jia compounds efficiently promotes the neuronal differentiation of neuroblastoma cells, intervening in tumorigenesis and the malignancy of neuroblastomas. Our results suggest that (hydroxyethyl) urea peptidomimetics containing unnatural amino acid substitutions could represent a novel class of γ-secretase inhibitors with enhanced stability, providing the basis for the further development of effective therapeutics for AD and neuroblastomas. Copyright