Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists

Shintaro Ban; Jun Ichi Kasuga; Izumi Nakagome; Hiromi Nobusada; Fusako Takayama; Shuichi Hirono; Hiromu Kawasaki; Yuichi Hashimoto; Hiroyuki Miyachi

doi:10.1016/j.bmc.2011.03.064

Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists

Shintaro Ban, Jun Ichi Kasuga, Izumi Nakagome, Hiromi Nobusada, Fusako Takayama, Shuichi Hirono, Hiromu Kawasaki, Yuichi Hashimoto, Hiroyuki Miyachi

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

17 Citations (Scopus)

Abstract

A series of α-ethylphenylpropanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) α-selective agonists, based on our PPARα/δ dual agonist 3 as a lead compound. Structure-activity relationship studies clearly indicated that the steric bulkiness and position of the distal hydrophobic tail part are critical for PPARα agonistic activity and PPARα selectivity, as had been predicted from a molecular-modeling study. A representative compound blocked the progression of nonalcoholic steatohepatitis (NASH) in an animal model.

Original language	English
Pages (from-to)	3183-3191
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	10
DOIs	https://doi.org/10.1016/j.bmc.2011.03.064
Publication status	Published - May 15 2011

ASJC Scopus subject areas

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

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10.1016/j.bmc.2011.03.064

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Ban, S., Kasuga, J. I., Nakagome, I., Nobusada, H., Takayama, F., Hirono, S., Kawasaki, H., Hashimoto, Y., & Miyachi, H. (2011). Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists. Bioorganic and Medicinal Chemistry, 19(10), 3183-3191. https://doi.org/10.1016/j.bmc.2011.03.064

Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists. / Ban, Shintaro; Kasuga, Jun Ichi; Nakagome, Izumi et al.
In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 10, 15.05.2011, p. 3183-3191.

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

Ban, S, Kasuga, JI, Nakagome, I, Nobusada, H, Takayama, F, Hirono, S, Kawasaki, H, Hashimoto, Y & Miyachi, H 2011, 'Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists', Bioorganic and Medicinal Chemistry, vol. 19, no. 10, pp. 3183-3191. https://doi.org/10.1016/j.bmc.2011.03.064

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abstract = "A series of α-ethylphenylpropanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) α-selective agonists, based on our PPARα/δ dual agonist 3 as a lead compound. Structure-activity relationship studies clearly indicated that the steric bulkiness and position of the distal hydrophobic tail part are critical for PPARα agonistic activity and PPARα selectivity, as had been predicted from a molecular-modeling study. A representative compound blocked the progression of nonalcoholic steatohepatitis (NASH) in an animal model.",

author = "Shintaro Ban and Kasuga, {Jun Ichi} and Izumi Nakagome and Hiromi Nobusada and Fusako Takayama and Shuichi Hirono and Hiromu Kawasaki and Yuichi Hashimoto and Hiroyuki Miyachi",

note = "Funding Information: This work was supported in part by the Targeted Proteins Research Program of the Japan Science and Technology Corporation (JST) and by the Uehara Memorial Foundation, and the Terumo Life Science Foundation.",

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AU - Kasuga, Jun Ichi

AU - Nakagome, Izumi

AU - Nobusada, Hiromi

AU - Takayama, Fusako

AU - Hirono, Shuichi

AU - Kawasaki, Hiromu

AU - Hashimoto, Yuichi

AU - Miyachi, Hiroyuki

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Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator- activated receptor (PPAR) α-selective agonists

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