Novel Notch-sparing γ-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 γ-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

School of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Screening of our library of peroxisome proliferator-activated receptor (PPAR) agonists yielded several phenylpropanoic acid-derived γ-secretase inhibitors (GSIs). Structure-activity relationship studies indicated that (R)-configuration of α-substituted phenylpropanoic acid structure and cinnamic acid structure is favorable to prepare Notch-sparing GSIs.

Original language	English
Pages (from-to)	5282-5285
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2010.06.131
Publication status	Published - Sept 1 2010

Keywords

Notch-sparing γ-secretase inhibitor
PPAR
γ-Secretase
γ-Secretase inhibitor

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2010.06.131

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title = "Novel Notch-sparing γ-secretase inhibitors derived from a peroxisome proliferator-activated receptor agonist library",

abstract = "Screening of our library of peroxisome proliferator-activated receptor (PPAR) agonists yielded several phenylpropanoic acid-derived γ-secretase inhibitors (GSIs). Structure-activity relationship studies indicated that (R)-configuration of α-substituted phenylpropanoic acid structure and cinnamic acid structure is favorable to prepare Notch-sparing GSIs.",

keywords = "Notch-sparing γ-secretase inhibitor, PPAR, γ-Secretase, γ-Secretase inhibitor",

author = "Motonori Kurosumi and Yoshino Nishio and Satoko Osawa and Hisayoshi Kobayashi and Takeshi Iwatsubo and Taisuke Tomita and Hiroyuki Miyachi",

note = "Funding Information: This work is supported in part by Grants-in-Aid for Young Scientists (S) from Japan Society for the Promotion of Science (JSPS), Scientific Research on Priority Areas {\textquoteleft}Research on Pathomechanisms of Brain Disorders{\textquoteright} from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), by Targeted Proteins Research Program of the Japan Science and Technology Corporation (JST) and by Core Research for Evolutional Science and Technology of JST, Japan.",

year = "2010",

month = sep,

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doi = "10.1016/j.bmcl.2010.06.131",

language = "English",

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T1 - Novel Notch-sparing γ-secretase inhibitors derived from a peroxisome proliferator-activated receptor agonist library

AU - Kurosumi, Motonori

AU - Nishio, Yoshino

AU - Osawa, Satoko

AU - Kobayashi, Hisayoshi

AU - Iwatsubo, Takeshi

AU - Tomita, Taisuke

AU - Miyachi, Hiroyuki

N1 - Funding Information: This work is supported in part by Grants-in-Aid for Young Scientists (S) from Japan Society for the Promotion of Science (JSPS), Scientific Research on Priority Areas ‘Research on Pathomechanisms of Brain Disorders’ from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), by Targeted Proteins Research Program of the Japan Science and Technology Corporation (JST) and by Core Research for Evolutional Science and Technology of JST, Japan.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Screening of our library of peroxisome proliferator-activated receptor (PPAR) agonists yielded several phenylpropanoic acid-derived γ-secretase inhibitors (GSIs). Structure-activity relationship studies indicated that (R)-configuration of α-substituted phenylpropanoic acid structure and cinnamic acid structure is favorable to prepare Notch-sparing GSIs.

AB - Screening of our library of peroxisome proliferator-activated receptor (PPAR) agonists yielded several phenylpropanoic acid-derived γ-secretase inhibitors (GSIs). Structure-activity relationship studies indicated that (R)-configuration of α-substituted phenylpropanoic acid structure and cinnamic acid structure is favorable to prepare Notch-sparing GSIs.

KW - Notch-sparing γ-secretase inhibitor

KW - PPAR

KW - γ-Secretase

KW - γ-Secretase inhibitor

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JF - Bioorganic and Medicinal Chemistry Letters

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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