Synthesis and SAR of hydroxyethylamine based phenylcarboxyamides as inhibitors of BACE.
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.
Wu
Yong-Jin
YJ
Neuroscience Discovery Chemistry, Bristol-Myers Squibb Research and Development, Wallingford, CT 06492, USA. yong-jin.wu@bms.com
Zhang
Yunhui
Y
Good
Andrew C
AC
Burton
Catherine R
CR
Toyn
Jeremy H
JH
Albright
Charles F
CF
Macor
John E
JE
Thompson
Lorin A
LA
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014162:Transfection
D001549:Benzamides; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases