| Literature DB >> 24900403 |
Matthew R Kaller1, Scott S Harried1, Brian Albrecht2, Patricia Amarante1, Safura Babu-Khan1, Michael D Bartberger1, James Brown1, Ryan Brown2, Kui Chen1, Yuan Cheng1, Martin Citron1, Michael D Croghan1, Russell Graceffa2, Dean Hickman1, Ted Judd1, Chuck Kriemen2, Daniel La2, Vivian Li1, Patricia Lopez1, Yi Luo1, Craig Masse2, Holger Monenschein1, Thomas Nguyen1, Lewis D Pennington1, Tisha San Miguel1, E Allen Sickmier1, Robert C Wahl1, Matthew M Weiss2, Paul H Wen1, Toni Williamson1, Stephen Wood1, May Xue1, Bryant Yang1, Jianhua Zhang1, Vinod Patel2, Wenge Zhong1, Stephen Hitchcock1.
Abstract
β-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against β-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce Aβ40 levels in plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led to the discovery of inhibitor 16 as a novel, potent, and orally efficacious BACE inhibitor.Entities:
Keywords: Alzheimer's disease (AD); hydroxyethylamine (HEA) isostere; β-site amyloid precursor protein cleaving enzyme (BACE)
Year: 2012 PMID： 24900403 PMCID： PMC4025811 DOI： 10.1021/ml3000148
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345