In 2015,Butler, Christopher R.; Brodney, Michael A.; Beck, Elizabeth M.; Barreiro, Gabriela; Nolan, Charles E.; Pan, Feng; Vajdos, Felix; Parris, Kevin; Varghese, Alison H.; Helal, Christopher J.; Lira, Ricardo; Doran, Shawn D.; Riddell, David R.; Buzon, Leanne M.; Dutra, Jason K.; Martinez-Alsina, Luis A.; Ogilvie, Kevin; Murray, John C.; Young, Joseph M.; Atchison, Kevin; Robshaw, Ashley; Gonzales, Cathleen; Wang, Jinlong; Zhang, Yong; O’Neill, Brian T. published 《Discovery of a Series of Efficient, Centrally Efficacious BACE1 Inhibitors through Structure-Based Drug Design》.Journal of Medicinal Chemistry published the findings.Related Products of 6149-41-3 The information in the text is summarized as follows:
The identification of centrally efficacious β-secretase (BACE1) inhibitors for the treatment of Alzheimer’s disease (AD) has historically been thwarted by an inability to maintain alignment of potency, brain availability, and desired absorption, distribution, metabolism, and excretion (ADME) properties. In this paper, the authors describe a series of truncated, fused thioamidines that are efficiently selective in garnering BACE1 activity without simultaneously inhibiting the closely related cathepsin D or neg. impacting brain penetration and ADME alignment, as exemplified by I. Upon oral administration, these inhibitors exhibit robust brain availability and are efficacious in lowering central Amyloid β (Aβ) levels in mouse and dog. In addition, chronic treatment in aged PS1/APP mice effects a decrease in the number and size of Aβ-derived plaques. Most importantly, evaluation of I in a 2-wk exploratory toxicol. study revealed no accumulation of autofluorescent material in retinal pigment epithelium or histol. findings in the eye, issues observed with earlier BACE1 inhibitors. The experimental process involved the reaction of Methyl 3-hydroxypropanoate(cas: 6149-41-3Related Products of 6149-41-3)
Methyl 3-hydroxypropanoate(cas: 6149-41-3) belongs to esters with low molecular weight are commonly used as fragrances and found in essential oils and pheromones. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Related Products of 6149-41-3
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Ester – an overview | ScienceDirect Topics