1043922-50-4Relevant articles and documents
A comparative study of warheads for design of cysteine protease inhibitors
Silva, Daniel G.,Ribeiro, Jean F.R.,De Vita, Daniela,Cianni, Lorenzo,Franco, Caio Haddad,Freitas-Junior, Lucio H.,Moraes, Carolina Borsoi,Rocha, Josmar R.,Burtoloso, Antonio C.B.,Kenny, Peter W.,Leit?o, Andrei,Montanari, Carlos A.
supporting information, p. 5031 - 5035 (2017/10/24)
The effects on potency of cruzain inhibition of replacing a nitrile group with alternative warheads were explored. The oxime was almost an order of magnitude more potent than the corresponding nitrile and has the potential to provide access to the prime side of the catalytic site. Dipeptide aldehydes and azadipeptide nitriles were found to be two orders of magnitude more potent cruzain inhibitors than the corresponding dipeptide nitriles although potency differences were modulated by substitution at P1 and P3. Replacement of the α methylene of a dipeptide aldehyde with cyclopropane led to a loss of potency of almost three orders of magnitude. The vinyl esters and amides that were characterized as reversible inhibitors were less potent than the corresponding nitrile by between one and two orders of magnitude.
Structural optimization of azadipeptide nitriles strongly increases association rates and allows the development of selective cathepsin inhibitors
Frizler, Maxim,Lohr, Friederike,Furtmann, Norbert,Kl?s, Julia,Gütschow, Michael
supporting information; scheme or table, p. 396 - 400 (2011/03/18)
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
