190274-53-4

Basic information

• Product Name: SJA6017
• Synonyms: SJA6017;N-(4-FLUOROPHENYLSULFONYL)-L-VALYL-L-LEUCINAL;4-FLUORO-BENZENESULFONYL-VAL-LEU-ALDEHYDE;4-FLUORO-BENZENESULFONYL-VAL-L-LEUCINAL;CALPAIN INHIBITOR VI;SJA6017, 4-Fluoro-benzenesulfonyl-Val-L-leucinal
• CAS NO: 190274-53-4
• Molecular Formula: C₁₇H₂₅FN₂O₄S
• Molecular Weight: 372.45
• Mol File: 190274-53-4.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• CAS DataBase Reference: SJA6017(CAS DataBase Reference)
• NIST Chemistry Reference: SJA6017(190274-53-4)
• EPA Substance Registry System: SJA6017(190274-53-4)

Safety Data

• Hazardous Substances Data: 190274-53-4(Hazardous Substances Data)

Usage

Description

Calpain inhibitor VI is an inhibitor of the calcium-dependent cysteine proteases μ-calpain (calpain-1; IC50 = 7.5 nM) and m-calpain (calpain-2; IC50 = 78 nM). It also inhibits cathepsins B and L (IC50s = 15 and 1.6 nM, respectively). It is selective for these calpains and cathepsins over other cysteine and serine proteases, factor VIIa, factor Xa, trypsin, chymotrypsin, and proteasome. In an in vitro porcine model of cataract, calpain inhibitor VI decreases the degree of cataract by 40% when used at a concentration of 0.8 μM. It also prevents cataract formation induced by selenite in rats when administered at a dose of 100 mg/kg for 4 days. Calpain inhibitor VI improves functional outcome and reduces apoptotic cell death in a rat model of spinal cord injury.

Upstream product

• 4070-48-8 L-Valine methyl ester 
• 97801-48-4 (S)-2-(4-fluorobenzenesulfonylamino)-3-methylbutanoic acid 
• 190275-58-2 N-((4-fluorophenyl)sulfonyl)-L-valine N-hydroxysuccinimide ester 
• 72-18-4 L-valine 
• 349-88-2 4-Fluorobenzenesulfonyl chloride 
• 797049-66-2 methyl (S)-2-(4-fluorobenzenesulfonylamino)-3-methylbutanoate 
• 797049-70-8 methyl (2'S,2S)-2-[2-(4-fluorobenzenesulfonylamino)-3-methylbutanoylamino]-4-methylpentanoate 
• 438003-82-8 (2S)-2-((4-fluorophenyl)sulfonylamino)-N-((1S)-1-(hydroxymethyl)-3-methylbutyl)-3-methylbutanamide 

Downstream Products

• 605665-79-0 (3S)-N-butyl-3-((2S)-2-((4-fluorophenyl)sulfonylamino)-3-methylbutanoylamino)-2-hydroxy-5-methylhexanamide 

Relevant articles and documents

NOVEL ALPHA-KETOAMIDE DERIVATIVE AND USE THEREOF

The present invention provides a compound represented by the formula (I): wherein R1, R2 and R3 each represents a lower alkyl group.

Exploration of cornea permeable calpain inhibitors as anticataract agents

To explore cornea permeable calpain inhibitors, four compounds displaying different characteristics were designed and synthesized based on the known potent calpain inhibitor, peptidyl aldehyde SJA6017. Two approaches were adopted; an improvement in the physicochemical properties, and conversion of the active aldehyde. The water-soluble peptidyl aldehyde 1 containing a pyridine ring at the P3 site showed a modest inhibition against calpains and an improvement of corneal permeability in comparison with SJA6017. Replacement of the aldehyde of SJA6017 by an α-ketoamide provided compound 2 that was approximately equipotent with SJA6017, but it was extremely water-insoluble. However, compound 3, in which the aldehyde was converted into a cyclic hemiacetal, proved to be a less potent calpain inhibitor than SJA6017, but demonstrated excellent transcorneal permeability. Further modification generating the cyclic hemiacetal 4 containing a thiourea linker between the P3 and P2 sites exhibited potent inhibitory activities, high cornea permeability and excellent efficacy in the rat lens culture cataract model.

Pharmaceutical composition for prophylaxis and therapy of diseases associated with ocular fundus tissue cytography

A pharmaceutical composition for the prophylaxis and therapy of a disease arising from ocular fundus tissue cytopathy such as retinochoroidal disease, glaucoma, and posterior complication arising form photocoagulation, which contains, as an active ingredient, a compound of formula (I) wherein R1represents an alkyl group having 1 to 4 carbon atoms or an aryl group having 6 to 10 carbon atoms which is optionally substituted; R2and R3may be the same or different and each represents hydrogen or an alkyl group having 1 to 4 carbon atoms or R2and R3may jointly form a ring having 3 to 7 carbon atoms; and R4represents a lower alkyl group which substituted by aryl, cycloalkyl, or aromatic heterocyclic residue, or a pharmaceutically acceptable salt thereof.