diamide and imidazole

Efforts to transfer to aluminum the heterocyclic ligand of a ring-opened imidazole scandium complex, which was previously reported, are presented. A ring-opened imidazole aluminum compound was formed at 50 °C and characterized as a trialuminum complex. At high temperature (85 °C), the formation of an unusual scandium/aluminum methylidene was observed. The reaction products were characterized by standard spectroscopic techniques and X-ray crystallography. Density functional theory calculations were used to understand the electronic structure of the scandium/aluminum methylidene complex.

Topics: Aluminum Compounds; Crystallography, X-Ray; Diamide; Ferrous Compounds; Imidazoles; Ligands; Metallocenes; Models, Molecular; Organometallic Compounds; Scandium

The synthesis and structure-activity relationship (SAR) of a novel series of di-substituted imidazoles, derived from modification of DAPT, are described. Subsequent optimization led to identification of a highly potent series of inhibitors that contain a β-amine in the imidazole side-chain resulting in a robust in vivo reduction of plasma and brain Aβ in guinea pigs. The therapeutic index between Aβ reductions and changes in B-cell populations were studied for compound 10 h.

Topics: Alzheimer Disease; Amination; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Biological Assay; Diamide; Enzyme Activation; Enzyme Inhibitors; Guinea Pigs; HeLa Cells; Humans; Imidazoles; Inhibitory Concentration 50; Molecular Structure; Structure-Activity Relationship