1387564-76-2

Upstream product

• 13734-41-3 t-Boc-L-valine 
• 22945-49-9 tris(4-(methylthio)phenyl) phosphite 
• 1282624-42-3 benzyl 1-(bis(4-(methylthio)phenoxy)phosphoryl)-2-methylpropylcarbamate 
• 1073-72-9 4-hydroxythioanisole 

Downstream Products

• 1348251-08-0 bis(4-(methylthio)phenyl) (R)-1-((S)-1-((S)-2-(4-methoxybenzamido)-3-methylbutanoyl)pyrrolidine-2-carboxamido)-2-methylpropylphosphonate 
• 1387563-83-8 tert-butyl 2-(4-(2-((S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethoxy)phenoxy)acetate 
• 1387563-84-9 2-(4-(2-((S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethoxy)phenoxy)acetic acid 
• 1387563-86-1 tert-butyl 2-(3-(2-((S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethyl)-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)acetate 
• 1387563-88-3 2-(3-(2-((S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethyl)-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)acetic acid 
• 1387563-87-2 tert-butyl 2-(3-(2-((S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethyl)-5-methyl-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)acetate 
• 1387563-89-4 2-(3-(2-((S)-1-((S)-2-((R)-1-(bis(4-(methylthio)phenoxy)-phosphoryl)-2-methylpropylcarbamoyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylamino)-2-oxoethyl)-5-methyl-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)acetic acid 
• 1387565-29-8 C₂HF₃O₂*C₂₈H₄₀N₃O₅PS₂ 

Relevant academic research and scientific papers

A BODIPY-Tagged Phosphono Peptide as Activity-Based Probe for Human Leukocyte Elastase

Human leukocyte elastase plays a crucial role in a variety of inflammatory disorders and represents an important subject of biomedical studies. The chemotype of peptidic phosphonates was employed for the design of a new activity-based probe for human leukocyte elastase. Its structure combines the phosphonate warhead with an adequate peptide portion and a BODIPY fluorophore with a clickable ethinylphenyl moiety at meso position. The probe 6 was assembled by copper-catalyzed alkyne-azide 1,3-dipolar cycloaddition. It was characterized as an active site-directed elastase inhibitor exhibiting a second-order rate constant of inactivation of 88400 M-1s-1. The suitability of 6 as a fluorescent probe for human leukocyte elastase was demonstrated by in-gel fluorescence analysis. Labeling experiments and inhibition data toward a panel of related proteases underlined the selectivity of the probe for the targeted leukocyte elastase.

Human neutrophil elastase phosphonic inhibitors with improved potency of action

Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of α-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a kinact/KI of 2353000 M-1 s -1, which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.