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Characterization of a Unique Co-crystal of the BACE1 Inhibitor Verubecestat and a Reaction Intermediate: Implications for the Development of a Commercial Manufacturing Process
journal contribution
posted on 2018-02-22, 00:00 authored by Laura Artino, Richard Varsolona, Andrew P. J. Brunskill, William J. Morris, David A. Thaisrivongs, Jacob H. Waldman, Thomas W. Lyons, Yanke XuVerubecestat is an inhibitor of beta-site
amyloid precursor protein
cleaving enzyme 1 (BACE1) that is currently under clinical evaluation
for the treatment of prodromal Alzheimer’s disease. This article
describes the characterization of a co-crystal composed of a HBr salt
of verubecestat and a HBr salt of a reaction intermediate as the components.
This unique co-crystal was formed during production of a multikilogram
batch of verubecestat. The impact of this observation is discussed,
followed by the description of a modified procedure that served to
prevent the formation of this highly unusual crystalline material.
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characterizationmultikilogramIntermediateCo-crystalco-crystalimpactHBr saltCommercial Manufacturing Process VerubecestatAlzheimerevaluationmaterialprodromalcomponentformationarticleImplicationUniqueBACE 1 Inhibitor VerubecestatCharacterizationverubecestatprocedurebatchinhibitorbeta-site amyloid precursor protein cleaving enzyme 1
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