1215868-60-2Relevant academic research and scientific papers
Inhibitors of β-site amyloid precursor protein cleaving enzyme (BACE1): Identification of (S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′ H -spiro[chromeno[2,3- b ]pyridine-5,4′-oxazol]-2′-amine (AMG-8718)
Dineen, Thomas A.,Chen, Kui,Cheng, Alan C.,Derakhchan, Katayoun,Epstein, Oleg,Esmay, Joel,Hickman, Dean,Kreiman, Chuck E.,Marx, Isaac E.,Wahl, Robert C.,Wen, Paul H.,Weiss, Matthew M.,Whittington, Douglas A.,Wood, Stephen,Fremeau, Robert T.,White, Ryan D.,Patel, Vinod F.
, p. 9811 - 9831 (2015/02/05)
We have previously shown that the aminooxazoline xanthene scaffold can generate potent and orally efficacious BACE1 inhibitors although certain of these compounds exhibited potential hERG liabilities. In this article, we describe 4-aza substitution on the xanthene core as a means to increase BACE1 potency while reducing hERG binding affinity. Further optimization of the P3 and P2′ side chains resulted in the identification of 42 (AMG-8718), a compound with a balanced profile of BACE1 potency, hERG binding affinity, and Pgp recognition. This compound produced robust and sustained reductions of CSF and brain Aβ levels in a rat pharmacodynamic model and exhibited significantly reduced potential for QTc elongation in a cardiovascular safety model.
AMINO-ISO-INDOLE, AMINO-AZA-ISO-INDOLE, AMINO-DIHYDROISOQUINOLINE AND AMINO-BENZOXAZINE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
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, (2012/02/15)
The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer?s disease (AD) and related conditions. In one embodiment, t
SPIRO-AMINO-IMIDAZO-FUSED HETEROCYCLIC COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
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, (2012/09/10)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I, wherein variables A1, A3, A4, A5, A6, A8, R2, R7, X, Y and Z of Formula I are defined here
5-AMINO-OXAZEPINE AND 5-AMINO-THIAZEPANE COMPOUNDS AS BETA-SECRETASE ANTAGONISTS AND METHODS OF USE
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, (2012/08/28)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I); wherein variables A1, A3, A4, A5, A6, As, R2, R7, X and Y of Formula (I) are defined here
SPIRO-AMINO-IMIDAZOLONE AND SPIRO-AMINO-DIHYDRO-PYRIMIDINONE COMPOUNDS AS BETA-SECRETASE MODULATORS AND METHODS OF USE
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, (2012/06/15)
The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula (I), wherein variables A1, A3, A4, A5, A6/su
