Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides as potent gamma-secretase inhibitors

Michael G Yang; Jian-Liang Shi; Dilip P Modi; Jennifer Wells; Brian M Cochran; Mark A Wolf; Lorin A Thompson; Mercy M Ramanjulu; Arthur H Roach; Robert Zaczek; David W Robertson; Ruth R Wexler; Richard E Olson

doi:10.1016/j.bmcl.2007.04.102

Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides as potent gamma-secretase inhibitors

Bioorg Med Chem Lett. 2007 Jul 15;17(14):3910-5. doi: 10.1016/j.bmcl.2007.04.102. Epub 2007 May 3.

Authors

Michael G Yang¹, Jian-Liang Shi, Dilip P Modi, Jennifer Wells, Brian M Cochran, Mark A Wolf, Lorin A Thompson, Mercy M Ramanjulu, Arthur H Roach, Robert Zaczek, David W Robertson, Ruth R Wexler, Richard E Olson

Affiliation

¹ Bristol-Myers Squibb Co., Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. michael.yang@bms.com

PMID: 17502143
DOI: 10.1016/j.bmcl.2007.04.102

Abstract

We report the synthesis of benzoazepine-derived cyclic malonamides (2) and aminoamides (3) as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease. The in vitro structure-activity relationships of 2 and 3 along with dog pharmacokinetic results are described.

MeSH terms

Amides / pharmacology*
Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Azepines / chemical synthesis
Azepines / chemistry*
Azepines / pharmacology*
Cyclization
Models, Molecular
Structure-Activity Relationship

Substances

Amides
Azepines
Amyloid Precursor Protein Secretases