Butler, Christopher R. published the artcileAminomethyl-Derived Beta Secretase (BACE1) Inhibitors: Engaging Gly230 without an Anilide Functionality, Safety of 3-(Trifluoromethyl)oxetan-3-amine hydrochloride, the publication is Journal of Medicinal Chemistry (2017), 60(1), 386-402, database is CAplus and MEDLINE.
A growing subset of β-secretase (BACE1) inhibitors for the treatment of Alzheimer’s disease (AD) utilizes an anilide chemotype that engages a key residue (Gly230) in the BACE1 binding site. Although the anilide moiety affords excellent potency, it simultaneously introduces a third hydrogen bond donor that limits brain availability and reveals a potential metabolic site leading to the formation of an aniline, a structural motif of potential safety concern. The authors report herein an alternative aminomethyl linker that delivers similar potency and improved brain penetration relative to the amide moiety. Optimization of this series identified analogs with an excellent balance of ADME properties and potency, however potential drug-drug interactions (DDI) were predicted based on CYP2D6 affinities. Generation and anal. of key BACE1 and CYP2D6 crystal structures identified strategies to obviate the DDI liability, leading to compound I which exhibits robust in vivo efficacy as a BACE1 inhibitor.
Journal of Medicinal Chemistry published new progress about 1268883-21-1. 1268883-21-1 belongs to quinuclidine, auxiliary class Trifluoromethyl,Fluoride,Oxetane,Salt,Amine, name is 3-(Trifluoromethyl)oxetan-3-amine hydrochloride, and the molecular formula is C4H7ClF3NO, Safety of 3-(Trifluoromethyl)oxetan-3-amine hydrochloride.
Referemce:
https://en.wikipedia.org/wiki/Quinuclidine,
Quinuclidine | C7H13N | ChemSpider