1227306-82-2Relevant academic research and scientific papers
Generation of Leads for γ-Secretase Modulation
Mandal, Mihirbaran,Buevich, Alexei,Caldwell, John P.,Hyde, Lynn,Huang, Xianhai,Liu, Xiaoxiang,Mckittrick, Brian,Mazzola, Robert D.,Pissarnitski, Dmitri,Palani, Anandan,Zhang, Lili,Parker, Eric,Xiao, Li,Rindgen, Diane,Zhu, Zhaoning
, p. 8216 - 8230 (2020/09/21)
Herein, we disclose three structurally differentiated γ-secretase modulators (GSMs) based on an oxadiazine scaffold. The analogues from series I potently inhibit the generation of Aβ42 in vitro when the substituents at 3 and 4 positions of the oxadiazine moiety adopt an α orientation (cf. 11). To address the concern around potential reactivity of the exocyclic double bond present in series I toward nucleophilic attack, compounds containing either an endocyclic double bond, such as 20 (series II), or devoid of an olefinic moiety, such as 27 (series III), were designed and validated as novel GSMs. Compound 11 and azepine 20 exhibit robust lowering of CSF Aβ42 in rats treated with a 30 mg/kg oral dose.
GAMMA SECRETASE MODULATORS
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Page/Page column 136, (2010/06/15)
In its many embodiments, the present invention provides a novel class of heterocyclic compounds of Group A or Group, as defined herein, as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions
