104802-07-5

Upstream product

• 21691-53-2 L-leucine tert-butyl ester 
• 2748-02-9 L-leucine tert-butyl ester hydrochloride 
• 3173-56-6 benzyl isothiocyanate 

Downstream Products

• 197855-46-2 (S)-2-(3-Benzyl-ureido)-4-methyl-pentanoic acid (1-benzyl-3-fluoro-2-hydroxy-propyl)-amide 
• 1259945-81-7 N-(benzylcarbamoyl)-leucyl-methylazaalanine-nitrile 
• 1259946-56-9 N-(benzylcarbamoyl)-leucine 1,2-dimethylhydrazide 

Relevant academic research and scientific papers

Structural optimization of azadipeptide nitriles strongly increases association rates and allows the development of selective cathepsin inhibitors

Using the example of cathepsin K, we demonstrate the design of highly potent and selective azadipeptide nitrile inhibitors. A systematic scan with respect to P2 and P3 substituents was carried out. Structural modifications strongly affected the enzyme-inh

Synthesis and biological activity of a series of potent fluoromethyl ketone inhibitors of recombinant human calpain I

Calpain I, an intracellular cysteine protease, has been implicated in the neurodegeneration following an episode of stroke. In this paper, we report on a series of potent dipeptide fluoromethyl ketone inhibitors of recombinant human calpain I (rh calpain I). SAR studies revealed that while calpain I tolerates a variety of hydrophobic groups at the P1 site, Leu at P2 is preferred. However, the nature of the N-terminal capping group has a significant effect on the inhibitory activity of this series of compounds. Compound 4e [(1,2,3,4-tetrahydroisoquinolin-2-yl)carbonyl-Leu-D,L-Phe- CH2F], having a tetrahydroisoquinoline containing urea as the N-terminal capping group, is the most potent dipeptide fluoromethyl ketone inhibitor of calpain 1 (with a second-order rate constant for inactivation of 276 000 M- 1 s-1) yet reported; tripeptide 4k (Cbz-Leu-Leu-D,L-Phe-CH2F) is equipotent. A number of compounds presented in this study displayed excellent selectivity for calpain I over cathepsins B and L, two related cysteine proteases. Compounds which exhibited good inhibitory activity in the assay against isolated rh calpain I also inhibited intracellular calpain I in a human cell line. Thus, in an intact cell assay, compounds 4e and 4k inhibited calpain I with IC50 values of 0.2 and 0.1 μM, respectively. Finally, we also disclose the first example of fluorination of a dipeptide enol silyl ether to generate the corresponding dipeptide fluoromethyl ketone.