Novel Notch-sparing gamma-secretase inhibitors derived from a peroxisome proliferator-activated receptor agonist library.
Screening of our library of peroxisome proliferator-activated receptor (PPAR) agonists yielded several phenylpropanoic acid-derived gamma-secretase inhibitors (GSIs). Structure-activity relationship studies indicated that (R)-configuration of alpha-substituted phenylpropanoic acid structure and cinnamic acid structure is favorable to prepare Notch-sparing GSIs.
Kurosumi
Motonori
M
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.
Nishio
Yoshino
Y
Osawa
Satoko
S
Kobayashi
Hisayoshi
H
Iwatsubo
Takeshi
T
Tomita
Taisuke
T
Miyachi
Hiroyuki
H
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists*; D051880:Receptors, Notch / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D047495:PPAR gamma; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases