1402001-80-2Relevant academic research and scientific papers
Design of pyridopyrazine-1,6-dione γ-secretase modulators that align potency, MDR efflux ratio, and metabolic stability
Pettersson, Martin,Johnson, Douglas S.,Humphrey, John M.,Butler, Todd W.,Am Ende, Christopher W.,Fish, Benjamin A.,Green, Michael E.,Kauffman, Gregory W.,Mullins, Patrick B.,O'Donnell, Christopher J.,Stepan, Antonia F.,Stiff, Cory M.,Subramanyam, Chakrapani,Tran, Tuan P.,Vetelino, Beth Cooper,Yang, Eddie,Xie, Longfei,Bales, Kelly R.,Pustilnik, Leslie R.,Steyn, Stefanus J.,Wood, Kathleen M.,Verhoest, Patrick R.
, p. 596 - 601 (2015/05/27)
Herein we describe the design and synthesis of a series of pyridopyrazine-1,6-dione γ-secretase modulators (GSMs) for Alzheimer's disease (AD) that achieve good alignment of potency, metabolic stability, and low MDR efflux ratios, while also maintaining favorable physicochemical properties. Specifically, incorporation of fluorine enabled design of metabolically less liable lipophilic alkyl substituents to increase potency without compromising the sp3-character. The lead compound 21 (PF-06442609) displayed a favorable rodent pharmacokinetic profile, and robust reductions of brain Aβ42 and Aβ40 were observed in a guinea pig time-course experiment.
Novel Bicyclic Pyridinones
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Page/Page column 46, (2012/10/08)
Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
