Synthesis and SAR of hydroxyethylamine based phenylcarboxyamides as inhibitors of BACE

Yong-Jin Wu; Yunhui Zhang; Andrew C Good; Catherine R Burton; Jeremy H Toyn; Charles F Albright; John E Macor; Lorin A Thompson

doi:10.1016/j.bmcl.2009.03.144

Synthesis and SAR of hydroxyethylamine based phenylcarboxyamides as inhibitors of BACE

Bioorg Med Chem Lett. 2009 May 15;19(10):2654-60. doi: 10.1016/j.bmcl.2009.03.144. Epub 2009 Apr 5.

Authors

Yong-Jin Wu¹, Yunhui Zhang, Andrew C Good, Catherine R Burton, Jeremy H Toyn, Charles F Albright, John E Macor, Lorin A Thompson

Affiliation

¹ Neuroscience Discovery Chemistry, Bristol-Myers Squibb Research and Development, Wallingford, CT 06492, USA. yong-jin.wu@bms.com

PMID: 19375914
DOI: 10.1016/j.bmcl.2009.03.144

Abstract

A series of N-((2S,3R)-1-(3,5-difluorophenyl)-3-hydroxy-4-(3-methoxybenzylamino)-butan-2-yl)benzamides has been synthesized as BACE inhibitors. A variety of P2 and P3 substituents has been explored, and these efforts have culminated in the identification of several 1,3,5-trisubstituted phenylcarboxyamides with potent BACE inhibitory activity.

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Amyloid Precursor Protein Secretases / metabolism
Benzamides / chemical synthesis*
Benzamides / chemistry
Benzamides / pharmacology
Cell Line
Humans
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology
Structure-Activity Relationship
Transfection

Substances

Benzamides
Protease Inhibitors
Amyloid Precursor Protein Secretases