Fujimoto, Kazuki published the artcileStructure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective β-Secretase (BACE1) Inhibitors over BACE2, Computed Properties of 401-55-8, the publication is Journal of Medicinal Chemistry (2021), 64(6), 3075-3085, database is CAplus and MEDLINE.
BACE1 is an attractive target for disease-modifying treatment of Alzheimer′s disease. BACE2, having high homol. around the catalytic site, poses a critical challenge to identifying selective BACE1 inhibitors. Recent evidence indicated that BACE2 has various roles in peripheral tissues and the brain, and therefore, the chronic use of nonselective inhibitors may cause side effects derived from BACE2 inhibition. Crystallog. anal. of the nonselective inhibitor verubecestat identified explicit water mols. with different levels of free energy in the S2′ pocket. Structure-based design targeting them enabled the identification of propynyl oxazine 3 with improved selectivity. Further optimization efforts led to the discovery of compound 6 with high selectivity. The cocrystal structures of 7, a close analog of 6, bound to BACE1 and BACE2 confirmed that one of the explicit water mols. is displaced by the propynyl group, suggesting that the difference in the relative water displacement cost may contribute to the improved selectivity.
Journal of Medicinal Chemistry published new progress about 401-55-8. 401-55-8 belongs to bromides-buliding-blocks, auxiliary class Fluoride,Bromide,Aliphatic hydrocarbon chain,Ester, name is Ethylbromofluoroacetate, and the molecular formula is C4H6BrFO2, Computed Properties of 401-55-8.
Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary