Thiazole-diamides as potent gamma-secretase inhibitors.
The thiazole-diamide series (1) has been identified as highly potent gamma-secretase inhibitors. Several representative compounds showed IC(50) values of <0.3 nM. The synthesis and SAR, as well as a radiolabeled synthesis of [(3)H]-2a, are described.
Chen
Yuhpyng L
YL
Department of Medicinal Chemistry, PGRD, Pfizer Inc., Connecticut, Groton, CT 06340, USA. yuhpyng888@yahoo.com
Cherry
Kevin
K
Corman
Michael L
ML
Ebbinghaus
Charles F
CF
Gamlath
Chandra B
CB
Liston
Dane
D
Martin
Barbara-Anne
BA
Oborski
Christine E
CE
Sahagan
Barbara G
BG
D000478:Alkylation; D000586:Amination; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002474:Cell-Free System; D003958:Diamide / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
D013844:Thiazoles; D003958:Diamide; D053829:Amyloid Precursor Protein Secretases