152954-84-2Relevant academic research and scientific papers
Macrocyclic prolinyl acyl guanidines as inhibitors of β-secretase (BACE)
Boy, Kenneth M.,Guernon, Jason M.,Wu, Yong-Jin,Zhang, Yunhui,Shi, Joe,Zhai, Weixu,Zhu, Shirong,Gerritz, Samuel W.,Toyn, Jeremy H.,Meredith, Jere E.,Barten, Donna M.,Burton, Catherine R.,Albright, Charles F.,Good, Andrew C.,Grace, James E.,Lentz, Kimberley A.,Olson, Richard E.,Macor, John E.,Thompson, Lorin A.
, p. 5040 - 5047 (2015)
The synthesis, evaluation, and structure-activity relationships of a class of acyl guanidines which inhibit the BACE-1 enzyme are presented. The prolinyl acyl guanidine chemotype (7c), unlike compounds of the parent isothiazole chemotype (1), yielded compounds with good agreement between their enzymatic and cellular potency as well as a reduced susceptibility to P-gp efflux. Further improvements in potency and P-gp ratio were realized via a macrocyclization strategy. The in vivo profile in wild-type mice and P-gp effects for the macrocyclic analog 21c is presented.
N-Aryl Pyrrolidine Derivatives as Beta-Secretase Inhibitors
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Page/Page column 9, (2010/11/28)
There is provided a series of substituted N-aryl pyrrolidine derivatives of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R5′, R6, R7, and p as defined herein, their pharmaceutical compositions and methods of use. These compounds inhibit the processing of amyloid precursor protein (APP) by β-secretase and, more specifically, inhibit the production of Aβ-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to β-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.
