877078-89-2Relevant academic research and scientific papers
Monosubstituted γ-lactam and conformationally constrained 1,3-diaminopropan-2-ol transition-state isostere inhibitors of β-secretase (BACE)
Boy, Kenneth M.,Guernon, Jason M.,Shi, Jianliang,Toyn, Jeremy H.,Meredith, Jere E.,Barten, Donna M.,Burton, Catherine R.,Albright, Charles F.,Marcinkeviciene, Jovita,Good, Andrew C.,Tebben, Andrew J.,Muckelbauer, Jodi K.,Camac, Daniel M.,Lentz, Kimberley A.,Bronson, Joanne J.,Olson, Richard E.,MacOr, John E.,Thompson III, Lorin A.
, p. 6916 - 6924 (2011/12/22)
The synthesis, evaluation, and structure-activity relationships of a class of γ-lactam 1,3-diaminopropan-2-ol transition-state isostere inhibitors of BACE are discussed. Two strategies for optimizing lead compound 1a are presented. Reducing the overall size of the inhibitors resulted in the identification of γ-lactam 1i, whereas the introduction of conformational constraint on the prime-side of the inhibitor generated compounds such as the 3-hydroxypyrrolidine inhibitor 28n. The full in vivo profile of 1i in rats and 28n in Tg 2576 mice is presented.
Novel gamma-lactams as beta-secretase inhibitors
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Page/Page column 27, (2010/10/20)
There is provided a series of novel substituted gamma-lactams of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R1, R2, R4, R5 and R6 as defined herein, their ph
