Swahn, Britt-Marie published the artcileDesign and Synthesis of β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1) Inhibitors with in Vivo Brain Reduction of β-Amyloid Peptides, SDS of cas: 917471-30-8, the main research area is aminoisoindole BACE1 inhibitor brain reduction beta amyloid peptide.
The evaluation of a series of aminoisoindoles as β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors and the discovery of a clin. candidate drug for Alzheimer’s disease, (S)-32 (I, AZD3839), are described. The improvement in permeability properties by the introduction of fluorine adjacent to the amidine moiety, resulting in in vivo brain reduction of Aβ40, is discussed. Due to the basic nature of these compounds, they displayed affinity for the human ether-a-go-go related gene (hERG) ion channel. Different ways to reduce hERG inhibition and increase hERG margins for this series are described, culminating in (S)-16 (II) and (R)-41 (III) showing large in vitro margins with BACE1 cell IC50 values of 8.6 and 0.16 nM, resp., and hERG IC50 values of 16 and 2.8 μM, resp. Several compounds were advanced into pharmacodynamic studies and demonstrated significant reduction of β-amyloid peptides in mouse brain following oral dosing.
Journal of Medicinal Chemistry published new progress about Absolute configuration (enantiomer preference for enzyme binding). 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, SDS of cas: 917471-30-8.