1146699-69-5

Basic information

• Product Name: (R)-2-(4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide
• Synonyms: (R)-2-(4-Chloro-N-(4-Cyano-2-Fluorobenzyl) Phenylsulfonamido)-5,5,5-Trifluoropentanamide
• CAS NO: 1146699-69-5
• Molecular Formula: C₁₉H₁₆ClF₄N₃O₃S
• Molecular Weight: 477.860952
• Mol File: 1146699-69-5.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: (R)-2-(4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-2-(4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide(1146699-69-5)
• EPA Substance Registry System: (R)-2-(4-chloro-N-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide(1146699-69-5)

Safety Data

• Hazardous Substances Data: 1146699-69-5(Hazardous Substances Data)

Usage

General Description

The chemical (R)-2-(4-Chloro-n-(4-cyano-2-fluorobenzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide is a white to off-white crystalline powder that is used in pharmaceutical research. It is a sulfonamide compound with a trifluoropentanamide group, and it has a chlorine atom and a cyano group on the benzyl ring. This chemical may have potential uses in the development of new medications and in the study of biological processes. However, due to its complex structure and potential biological activity, it must be handled and studied with care and attention to safety protocols.

Upstream product

• 1146699-67-3 (R)-2-(4-chlorophenylsulfonamido)-5,5,5-trifluoropentanamide 
• 105942-09-4 4-(bromomethyl)-3-fluorobenzonitrile 

Downstream Products

• 1146699-70-8 (R)-2-(4-chloro-N-(2-fluoro-4-(N'-hydroxycarbamimidoyl)benzyl)phenylsulfonamido)-5,5,5-trifluoropentanamide 

Relevant articles and documents

Application of the bicyclo[1.1.1]pentane motif as a nonclassical phenyl ring bioisostere in the design of a potent and orally active γ-secretase inhibitor

Replacement of the central, para-substituted fluorophenyl ring in the γ-secretase inhibitor 1 (BMS-708,163) withthe bicyclo[1.1.1]pentane motif led to the discovery of compound 3, an equipotent enzyme inhibitor with significant improvements in passive permeability and aqueous solubility. The modified biopharmaceutical properties of 3 translated into excellent oral absorption characteristics (～4-fold Cmax and AUC values relative to 1) in a mouse model of γ-secretase inhibition. In addition, SAR studies into other fluorophenyl replacements indicate the intrinsic advantages of the bicyclo[1.1.1]pentane moiety over conventional phenyl ring replacements with respect to achieving an optimal balance of properties (e.g., γ-secretase inhibition, aqueous solubility/permeability, in vitro metabolic stability). Overall, this work enhances the scope of the [1.1.1]-bicycle beyond that of a mere spacer unit and presents a compelling case for its broader application as a phenyl group replacement in scenarios where the aromatic ring count impacts physicochemical parameters and overall drug-likeness.

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.