Revisiting glitazars: Thiophene substituted oxazole containing α-ethoxy phenylpropanoic acid derivatives as highly potent PPARα/γ dual agonists devoid of adverse effects in rodents

被引：20

作者：

Raval, Preeti ^{[1
,2
]}

Jain, Mukul ^{[1
]}

Goswami, Amitgiri ^{[1
]}

Basu, Sujay ^{[1
]}

Gite, Archana ^{[1
]}

Godha, Atul ^{[1
]}

Pingali, Harikishore ^{[1
]}

Raval, Saurin ^{[1
]}

Giri, Suresh ^{[1
]}

Suthar, Dinesh ^{[1
]}

Shah, Maanan ^{[1
]}

Patel, Pankaj ^{[1
]}

机构：

[1] Zydus Res Ctr, Ahmadabad 382210, Gujarat, India

[2] Maharaja Sayajirao Univ Baroda, Fac Sci, Dept Chem, Vadodara 390002, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 10期

关键词：

Metabolic syndrome; PPAR alpha/gamma dual agonist; Oxazole; Type; 2; diabetes; ACTIVATED RECEPTOR (PPAR)-ALPHA; INSULIN SENSITIVITY; ANTIDIABETIC AGENTS; PROLIFERATOR; FENOFIBRATE; DESIGN; THIAZOLIDINEDIONE; MURAGLITAZAR; GEMFIBROZIL; EXPRESSION;

D O I：

10.1016/j.bmcl.2011.03.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In an effort to develop safe and efficacious compounds for the treatment of metabolic disorders, novel thiophene substituted oxazole containing alpha-alkoxy-phenylpropanoic acid derivatives are designed as highly potent PPAR alpha/gamma dual agonists. These compounds were found to be efficacious at picomolar concentrations. Lead compound 18d has emerged as very potent PPAR alpha/gamma dual agonist demonstrating potent antidiabetic and lipid lowering activity at a very low dose and did not exhibit any significant signs of toxicity in rodents. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3103 / 3109

页数：7

共 3 条

[1] Design and synthesis of novel oxazole containing 1,3-Dioxane-2-carboxylic acid derivatives as PPAR α/γ dual agonists
Pingali, Harikishore
Jain, Mukul
Shah, Shailesh
Makadia, Pankaj
Zaware, Pandurang
Goel, Ashish
Patel, Megha
Giri, Suresh
Patel, Harilal
Patel, Pankaj
BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (15) : 7117 - U2
[2] Effects of modifications of the linker in a series of phenylpropanoic acid derivatives:: Synthesis, evaluation as PPARα/γ dual agonists, and X-ray crystallographic studies
Casimiro-Garcia, Agustin
Bigge, Christopher F.
Davis, Jo Ann
Padalino, Teresa
Pulaski, James
Ohren, Jeffrey F.
McConnell, Patrick
Kane, Christopher D.
Royer, Lori J.
Stevens, Kimberly A.
Auerbach, Bruce J.
Collard, Wendy T.
McGregor, Christine
Fakhoury, Stephen A.
Schaum, Robert P.
Zhou, Hairong
BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (09) : 4883 - 4907
[3] Design, synthesis, and evaluation of a novel series of α-substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor (PPAR) α/δ dual agonists for the treatment of metabolic syndrome
Kasuga, Jun-ichi
Yamasaki, Daisuke
Araya, Yoko
Nakagawa, Aya
Makishima, Makoto
Doi, Takefumi
Hashimoto, Yuichi
Miyachi, Hiroyuki
BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (24) : 8405 - 8414

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