1290541-27-3Relevant articles and documents
ASK1 INHIBITING AGENTS
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Page/Page column 153-154, (2018/09/08)
Provided are compounds of Formulas (I'), (I), (II') and (II), or pharmaceutically acceptable salts thereof, and methods for their use and production.
THERAPEUTIC COMPOUNDS AND USES THEREOF
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Page/Page column 90; 91, (2016/08/23)
The present invention relates to compounds of formula (I): and to salts thereof, wherein R1-R6 have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of TAF1. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various TAF1-mediated disorders.
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.
