1146699-67-3

Basic information

• Product Name: PentanaMide, 2-[[(4-chlorophenyl)sulfonyl]aMino]-5,5,5-trifluoro-, (2R)-
• Synonyms: PentanaMide, 2-[[(4-chlorophenyl)sulfonyl]aMino]-5,5,5-trifluoro-, (2R)-;N2-[(4-Chlorophenyl)sulfonyl]-5,5,5-trifluoro-D-norvalinamide;(R)-2-((4-chlorophenyl)sulfonamido)-5,5,5-trifluoropentanamide;(S)-2-((4-chlorophenyl)sulfonamido)-5,5,5-trifluoropentanamide
• CAS NO: 1146699-67-3
• Molecular Formula: C₁₁H₁₂ClF₃N₂O₃S
• Molecular Weight: 344.7377896
• Mol File: 1146699-67-3.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: PentanaMide, 2-[[(4-chlorophenyl)sulfonyl]aMino]-5,5,5-trifluoro-, (2R)-(CAS DataBase Reference)
• NIST Chemistry Reference: PentanaMide, 2-[[(4-chlorophenyl)sulfonyl]aMino]-5,5,5-trifluoro-, (2R)-(1146699-67-3)
• EPA Substance Registry System: PentanaMide, 2-[[(4-chlorophenyl)sulfonyl]aMino]-5,5,5-trifluoro-, (2R)-(1146699-67-3)

Safety Data

• Hazardous Substances Data: 1146699-67-3(Hazardous Substances Data)

Upstream product

• 1146699-58-2 (R)-2-amino-5,5,5-trifluoropentanamide hydrochloride 
• 98-60-2 4-chlorobenzenesulfonyl chloride 
• 1392848-78-0 C₁₁H₁₀Cl₂F₃NO₃S 
• 118311-18-5 5,5,5-trifluoro-2-oxopentanoic acid 
• 122565-29-1 (2R)-2-amino-5,5,5-trifluoropentanoic acid 

Downstream Products

• 1146699-69-5 (R)-2-[4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido]-5,5,5-trifluoropentanamide 
• 1146699-66-2 avagacestat 
• 1370705-43-3 (R)-2-[4-chloro-N-(3-cyanopropyl)phenylsulfonamido]-5,5,5-tri-fluoropentanamide 
• 1370705-47-7 (R)-2-{4-chloro-N-[(1-cyanocyclopropyl)methyl]-phenylsulfonamido}-5,5,5-trifluoropentanamide 
• 1370705-41-1 (R)-2-[4-chloro-N-(4-cyanobenzyl)phenylsulfonamido]-5,5,5-tri-fluoropentanamide 
• 1372118-36-9 (R)-2-{4-chloro-N-{[(1R,2R)-2-cyanocyclopropyl]methyl}-phenylsulfonamido}-5,5,5-trifluoropentanamide 
• 1372118-35-8 (R)-2-{4-chloro-N-{[(1S,2S)-2-cyanocyclopropyl]methyl}-phenylsulfonamido}-5,5,5-trifluoropentanamide 
• 1370705-44-4 (R)-2-[4-chloro-N-(4-cyanobutyl)phenylsulfonamido]-5,5,5-tri-fluoropentanamide 
• 1370705-42-2 (R)-2-[4-chloro-N-(2-cyanoethyl)phenylsulfonamido]-5,5,5-tri-fluoropentanamide 
• 1372118-37-0 (R)-2-{4-chloro-N-{[(1s,3r)-3-cyano-3-methylcyclobutyl]methyl}-phenylsulfonamido}-5,5,5-trifluoropentanamide 
• 1372118-38-1 (R)-2-{4-chloro-N-{[(1r,3s)-3-cyano-3-methylcyclobutyl]methyl}-phenylsulfonamido}-5,5,5-trifluoropentanamide 
• 1372118-39-2 (R)-2-{4-chloro-N-{[(1r,4r)-4-cyanocyclohexyl]methyl}-phenylsulfonamido}-5,5,5-trifluoropentanamide 
• 1370705-46-6 (R)-2-{4-chloro-N-{[(1r,3r)-3-cyanocyclobutyl]methyl}phenylsulfonamido}-5,5,5-trifluoropentanamide 
• 1370705-45-5 (R)-2-{4-chloro-N-{[(1s,3s)-3-cyanocyclobutyl]methyl}-phenylsulfonamido}-5,5,5-trifluoropentanamide 

Relevant articles and documents

Enzymatic preparation of an R-amino acid intermediate for a γ-secretase inhibitor

(R)-5,5,5-Trifluoronorvaline, an intermediate for a γ-secretase inhibitor (BMS-708163) under development, was initially prepared from the corresponding keto acid using a commercially available d-amino acid dehydrogenase for reductive amination and glucose dehydrogenase for cofactor recycling. This amino acid could also be prepared using a d-amino acid transaminase with alanine as the amino donor, but the transamination also requires lactate dehydrogenase, NAD, formate, and formate dehydrogenase to remove pyruvate in order to bring the reaction to completion. An effective proprietary d-amino acid dehydrogenase was constructed by modification of the d-diaminopimelic acid dehydrogenase gene from Bacillus sphaericus, and a glucose dehydrogenase gene was cloned from Gluconobacter oxidans. Both genes were expressed in the same strain of Escherichia coli, and the glutamate dehydrogenase gene was inactivated in the expression strain to eliminate background production of the S-amino acid and improve the ee of the product to 100%. The amino acid could be isolated or converted without isolation to a p-chlorophenylsulfonamide carboxamide intermediate needed for the synthetic route to the γ-secretase inhibitor development candidate.

NOVEL ALPHA-(N-SULFONAMIDO)ACETAMIDE COMPOUNDS INCORPORATING DEUTERIUM AS INHIBITORS OF BETA AMYLOID PEPTIDE PRODUCTION

The present disclosure provides novel deuterated alpha-(N-sulfonamido)acetamide compounds, their pharmaceutical composition, processes thereof and a method for the treatment of Alzheimer's disease, head trauma, traumatic brain injury, and/or dementia pugilistica and/or other conditions associated with β-amyloid peptide.

Discovery and evaluation of BMS-708163, a potent, selective and orally bioavailable γ-secretase inhibitor

During the course of our research efforts to develop a potent and selective γ-secretase inhibitor for the treatment of Alzheimer's disease, we investigated a series of carboxamide-substituted sulfonamides. Optimization based on potency, Notch/amyloid-β precursor protein selectivity, and brain efficacy after oral dosing led to the discovery of 4 (BMS-708163). Compound 4 is a potent inhibitor of γ-secretase (Aβ40 IC50 = 0.30 nM), demonstrating a 193-fold selectivity against Notch. Oral administration of 4 significantly reduced Aβ40 levels for sustained periods in brain, plasma, and cerebrospinal fluid in rats and dogs.

Novel Alpha-(N-Sulfonamido)Acetamide Compound as an Inhibitor of Beta Amyloid Peptide Production

The present invention provides a novel alpha-(N-sulfonamido)acetamide compound, its pharmaceutical composition, processes thereof and a method for the treatment of Alzheimer's disease and other conditions associated with β-amyloid peptide.