138695-77-9

Basic information

• Product Name: 7-<(N-tosylleucyl)amino>-4-chloro-3-methoxyisocoumarin
• Synonyms: 7-<(N-tosylleucyl)amino>-4-chloro-3-methoxyisocoumarin
• CAS NO: 138695-77-9
• Molecular Weight: 492.98
• Mol File: 138695-77-9.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: 7-<(N-tosylleucyl)amino>-4-chloro-3-methoxyisocoumarin(CAS DataBase Reference)
• NIST Chemistry Reference: 7-<(N-tosylleucyl)amino>-4-chloro-3-methoxyisocoumarin(138695-77-9)
• EPA Substance Registry System: 7-<(N-tosylleucyl)amino>-4-chloro-3-methoxyisocoumarin(138695-77-9)

Safety Data

• Hazardous Substances Data: 138695-77-9(Hazardous Substances Data)

Upstream product

• 62252-26-0 JLK 6 
• 61341-05-7 N-tosylleucine acid chloride 
• 62252-25-9 4-chloro-3-methoxy-7-nitroisocoumarin 
• 1220-80-0 (S)-4-methyl-2-(toluene-4-sulfonamido)pentanoic acid 

Relevant articles and documents

Effect of the 7-Amino Substituent on the Inhibitory Potency of Mechanism-Based Isocoumarin Inhibitors for Porcine Pancreatic and Human Neutrophil Elastases: A 1.85-Angstroem X-ray Structure of the Complex between Porcine Pancreatic Elastase and 7--4-chloro-...

A series of new acyl, urea, and carbonate derivatives of 7-amino-4-chloro-3-methoxyisocoumarin were synthesized and evaluated as irreversible inhibitors of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE).Inhibition of HNE is directly related to the hydrophobicity of the substituent on the 7-amino group.The N-Tos-Phe derivative (19) is the best HNE inhibitor with a second-order rate constant kobs/ = 200 000 M-1s-1.The closest analogue in this series, the 3,3-diphenylpropionyl derivative 5, had kobs/ = 130 000 M-1s-1 with HNE.In contrast to the Tos-Phe derivative 19, phenylacetyl derivative 2 and carbonates 22 and 25 gave extremely stable enzyme-inhibitor complexes with deacylation half-lives longer than 48 h with both elastases.N-Phenylurea derivative 25 was the best inhibitor for PPE with a second-order rate constant kobs/ = 7300 M-1s-1.The crystal structure of a complex of PPE with N-tosyl-Phe derivative 19 was determined at 1.85 Angstroem resolution and refined to a final R factor of 16.9percent.The isocoumarin forms an acyl enzyme with Ser-195, while His-57 is near the inhibitor, but not covalently linked.The Tos-Phe makes a few hydrophobic contacts with the S' subsites of PPE, but appears to be interacting primarily with itself in the PPE structure.This region of HNE is more hydrophobic and modeling indicates that the inhibitor would probably make additional contacts with the enzyme.