899838-06-3Relevant academic research and scientific papers
New Cathepsin D inhibitor library utilizing hydroxyethyl isosteres with cyclic tertiary amines
McConnell, Rose M.,Inapudi, Kalyani,Kadasala, Naveen,Yarlagadda, Karthika,Velusamy, Priya,McConnell, James S.,McConnell, Matthew S.,Trana, Carol,Green, Adam,Sayyar, Kelley
, p. 1146 - 1154,9 (2012/12/12)
The design and synthesis of hydroxyethylamine isosteres as inhibitors of cathepsin D based on SAR data have been accomplished. A library of 96 of these hydroxyethylamine isosteres are described and many have proven to be very potent inhibitors of human cathepsin D activity as measured using a fluorometric assay technique, via peptide substrate Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg- Leu-Gly-Lys(Methyl Red)-Glu-NH2. Compounds showing strongest inhibition of cathepsin D activity were those that contain a hydroxyethyl-N'-2- or N'-(4-chlorophenyl)piperazine moiety (IC50 values range from 0.55 to 8.5 nM), with N'-(2-pyrimidyl)piperizine (IC50 values range from 0.5 to 21.6 nM), with NN'- L-piperazinocolinamide (IC50 values range from 0.001 - 0.25 nM), or N-N'-L-piperazinocolin-N-methylamide (IC50 values range from 0.015 - 7.3 nM) .
