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structural development studies of subtype-selective ligands for peroxisome proliferator-activated receptors (ppars) based on the 3,4-disubstituted phenylpropanoic acid scaffold as a versatile template英文论文.pdf

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structural development studies of subtype-selective ligands for peroxisome proliferator-activated receptors (ppars) based on the 3,4-disubstituted phenylpropanoic acid scaffold as a versatile template英文论文

Hindawi Publishing Corporation PPAR Research Volume 2008, Article ID 689859, 15 pages doi:10.1155/2008/689859 Review Article Structural Development Studies of Subtype-Selective Ligands for Peroxisome Proliferator-Activated Receptors (PPARs) Based on the 3,4-Disubstituted Phenylpropanoic Acid Scaffold as a Versatile Template Hiroyuki Miyachi and Yuichi Hashimoto Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi Bunkyo-ku, Tokyo 113-0032, Japan Correspondence should be addressed to Hiroyuki Miyachi, miyachi@iam.u-tokyo.ac.jp Received 17 August 2007; Revised 9 November 2007; Accepted 26 December 2007 Recommended by F. Gregoire Improvements in our understanding of the functions of the nuclear receptor peroxisome proliferator-activated receptor (PPAR) subtypes as pleiotropic regulators of biological responses, including lipid, lipoprotein, glucose homeostasis, inﬂammation, diﬀerentiation and proliferation of various cancer cells, and memory, have provided an opportunity to develop novel PPAR ligands with characteristic subtype selectivity. Such ligands are not only chemical tools to investigate the functions of PPARs, but also candidates for the treatment of PPAR-mediated diseases, including metabolic syndrome, inﬂammation, dementia, and cancer. This minireview summarizes our work on the design, synthesis, and pharmacological evaluation of subtype-selective PPAR agonists based on the use of 3,4-disubstituted phenylpropanoic acid as a versatile template. Copyright © 2008 H. Miyachi and Y. Hashimoto. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. N