107202-61-9Relevant articles and documents
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) .
DIAMINOPROPANOL RENIN INHIBITORS
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, (2008/06/13)
Described are diaminopropanols of which are orally active and bind to renin to inhibit its activity. They are useful in the treatment or amelioration of diseases associated with elevated levels of renin activity or in the treatment of aspartic protease me
Ready access to stereodefined β-hydroxy-γ-amino acids. Enantioselective synthesis of fully protected cyclohexylstatine
Castejon, Patricia,Moyano, Albert,Pericas, Miquel A.,Riera, Antoni
, p. 7063 - 7086 (2007/10/03)
A convenient entry to enantiopure syn or anti β-hydroxy-γ-amino acids is described. The starting compounds for the synthesis, anti 3-amino-1,2-diols, are readily available in high enantiomeric purity through catalytic asymmetric epoxidation of an allylic alcohol and titanium-promoted oxirane opening. After adequate protection of the nitrogen, a stereodivergent sequence leads to both anti and syn N-Boc aminoalkyl epoxides. Subsequent regioselective ring-opening with cyanide, protection of the resulting secondary alcohol and nitrile to carboxyl conversion afford, in good yields, protected β-hydroxy-γ-amino acid belonging to either the anti (erythro) or syn (threo) series. This methodology has been applied to the enantioselective preparation of cyclohexylstatine, a key component of several aspartyl protease inhibitors, in fully protected form.