108468-00-4Relevant articles and documents
Benzazepine Dicarboxamide Compounds
-
Paragraph 0441; 0442, (2016/09/26)
This invention relates to novel benzazepine dicarboxamide compounds of the formula wherein R1 to R4 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are TLR agonists and may therefore be useful as medicaments for the treatment of diseases such as cancer, autoimmune diseases, inflammation, sepsis, allergy, asthma, graft rejection, graft-versus-host disease, immunodeficiencies, and infectious diseases.
Discovery of biphenylacetamide-derived inhibitors of BACE1 using de novo structure-based molecular design
Mok, N. Yi,Chadwick, James,Kellett, Katherine A. B.,Casas-Arce, Eva,Hooper, Nigel M.,Johnson, A. Peter,Fishwick, Colin W. G.
, p. 1843 - 1852 (2013/05/08)
β-Secretase (BACE1), the enzyme responsible for the first and rate-limiting step in the production of amyloid-β peptides, is an attractive target for the treatment of Alzheimer's disease. In this study, we report the application of the de novo fragment-based molecular design program SPROUT to the discovery of a series of nonpeptide BACE1 inhibitors based upon a biphenylacetamide scaffold. The binding affinity of molecules based upon this designed molecular scaffold was increased from an initial BACE1 IC50 of 323 μM to 27 μM following the synthesis of a library of optimized ligands whose structures were refined using the recently developed SPROUT-HitOpt software. Although a number of inhibitors were found to exhibit cellular toxicity, one compound in the series was found to have useful BACE1 inhibitory activity in a cellular assay with minimal cellular toxicity. This work demonstrates the power of an in silico fragment-based molecular design approach in the discovery of novel BACE1 inhibitors.
Covalent modification of glassy carbon surface with organic redox probes through diamine linkers using electrochemical and solid-phase synthesis methodologies
Ghanem, Mohamed A.,Chretien, Jean-Mathieu,Pinczewska, Aleksandra,Kilburn, Jeremy D.,Bartlett, Philip N.
experimental part, p. 4917 - 4927 (2010/02/28)
Various mono-Boc-protected diamines have been covalently grafted to glassy carbon electrodes by electrochemical oxidation of the free amine. After deprotection of the Boc group, anthraquinone and nitrobenzene probes were coupled to the linkers using solid-phase coupling reactions. X-Ray photoelectron spectroscopy and cyclic voltammetry were used to monitor the coupling efficiency, effect of linker length on the surface coverage and electron transfer between the attached redox probes and electrode. The anthraquinone surface coverage was found to decrease as the chain length of alkyl diamine linker increased and the electron transfer kinetics were found to be faster for the lower coverages and the longer, more flexible linkers. In the case of nitrobenzene, there was only a slightly change in coverage with increasing linker length. This electrochemical attachment of protected diamine linkers followed by solid-phase coupling provides a very versatile methodology for attaching a wide range of molecular architectures onto glassy carbon surfaces. The Royal Society of Chemistry 2008.
