Calpain Inhibitor VI

Base Information

• Chemical Name: Calpain Inhibitor VI
• CAS No.: 190274-53-4
• Molecular Formula: C17H25FN2O4S
• Molecular Weight: 372.461
• Nikkaji Number: J898.242B
• Pharos Ligand ID: QHNU2WAM434H
• ChEMBL ID: CHEMBL288365
• Mol file: 190274-53-4.mol

Synonyms:N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal;SJA 6017;SJA-6017;SJA6017

Chemical Property of Calpain Inhibitor VI

Chemical Property:

• PSA: 100.72000
• LogP: 3.72100
• XLogP3: 3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 9
• Exact Mass: 372.15190662
• Heavy Atom Count: 25
• Complexity: 537

Purity/Quality:

98%Min ^*data from raw suppliers

Calpain Inhibitor VI ≥95% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)CC(C=O)NC(=O)C(C(C)C)NS(=O)(=O)C1=CC=C(C=C1)F
• Isomeric SMILES: CC(C)C[C@@H](C=O)NC(=O)[C@H](C(C)C)NS(=O)(=O)C1=CC=C(C=C1)F
• 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.

Technology Process of Calpain Inhibitor VI

There total 9 articles about Calpain Inhibitor VI which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 73.0%

methyl (2'S,2S)-2-[2-(4-fluorobenzenesulfonylamino)-3-methylbutanoylamino]-4-methylpentanoate (797049-70-8) → N-((4-Fluorophenyl)sulfonyl)-L-valyl-L-leucinal (190274-53-4)

Guidance literature:

With diisobutylaluminium hydride; In dichloromethane; at -78 ℃; for 3h;

DOI:10.1071/CH04080

Reference yield: 60.0%

(2S)-2-((4-fluorophenyl)sulfonylamino)-N-((1S)-1-(hydroxymethyl)-3-methylbutyl)-3-methylbutanamide (438003-82-8) → N-((4-Fluorophenyl)sulfonyl)-L-valyl-L-leucinal (190274-53-4)

Guidance literature:

With sulfur trioxide pyridine complex; N-ethyl-N,N-diisopropylamine; In dichloromethane; dimethyl sulfoxide; at 20 ℃; for 0.666667h;

Reference yield:

4-Fluorobenzenesulfonyl chloride (349-88-2) → N-((4-Fluorophenyl)sulfonyl)-L-valyl-L-leucinal (190274-53-4)

Guidance literature:

Multi-step reaction with 4 steps

1: 95 percent / iPr₂NEt / CH₂Cl₂ / 4 h / Heating

2: 97 percent / KOH / H₂O; tetrahydrofuran / 3 h / 40 °C

3: 89 percent / BOP; iPr₂NEt / CH₂Cl₂ / 24 h

4: 73 percent / DIBALH / CH₂Cl₂ / 3 h / -78 °C

With potassium hydroxide; diisobutylaluminium hydride; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; dichloromethane; water;

DOI:10.1071/CH04080

upstream raw materials:

(2S)-2-((4-fluorophenyl)sulfonylamino)-N-((1S)-1-(hydroxymethyl)-3-methylbutyl)-3-methylbutanamide

methyl (2'S,2S)-2-[2-(4-fluorobenzenesulfonylamino)-3-methylbutanoylamino]-4-methylpentanoate

methyl (S)-2-(4-fluorobenzenesulfonylamino)-3-methylbutanoate

L-Valine methyl ester

Downstream raw materials:

(3S)-N-butyl-3-((2S)-2-((4-fluorophenyl)sulfonylamino)-3-methylbutanoylamino)-2-hydroxy-5-methylhexanamide

Refernces

• 1、 Payne, Richard J.,Brown, Karina M.,Coxon, James M.,Morton, James D.,Lee, Hannah Yun-Young,Abell, Andrew D.. "Peptidic aldehydes based on α- and β-amino acids: Synthesis, inhibition of m-Calpain, and anti-cataract properties". . p. 877 - 884. Retrieved 2007/10/03.
• 2、 Inoue, Jun,Nakamura, Masayuki,Cui, Ying-She,Sakai, Yusuke,Sakai, Osamu,Hill, Jeanette R.,Wang, Kevin K. W.,Yuen, Po-Wai. "Structure-activity relationship study and drug profile of N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal (SJA6017) as a potent calpain inhibitor". . p. 868 - 871. Retrieved 2007/10/03.