Novel Notch-sparing gamma-secretase inhibitors derived from a peroxisome proliferator-activated receptor agonist library

Motonori Kurosumi; Yoshino Nishio; Satoko Osawa; Hisayoshi Kobayashi; Takeshi Iwatsubo; Taisuke Tomita; Hiroyuki Miyachi

doi:10.1016/j.bmcl.2010.06.131

Novel Notch-sparing gamma-secretase inhibitors derived from a peroxisome proliferator-activated receptor agonist library

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5282-5. doi: 10.1016/j.bmcl.2010.06.131. Epub 2010 Jul 3.

Authors

Motonori Kurosumi¹, Yoshino Nishio, Satoko Osawa, Hisayoshi Kobayashi, Takeshi Iwatsubo, Taisuke Tomita, Hiroyuki Miyachi

Affiliation

¹ Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.

PMID: 20650635
DOI: 10.1016/j.bmcl.2010.06.131

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Enzyme Inhibitors / metabolism*
PPAR gamma / agonists*
Receptors, Notch / metabolism*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
PPAR gamma
Receptors, Notch
Amyloid Precursor Protein Secretases