Design, synthesis and evaluation of peroxisome proliferator-activated receptor α/γ dual agonists for the treatment of type 2 diabetes

被引:0
|
作者
Das, Saibal Kumar [1 ]
Abbineni, Chandrasekhar [1 ]
Rao, Krovvidi Venkata Lakshmi Narasimha [1 ]
Iqbal, Javed [1 ]
Babu, Ravi Krishna [1 ]
Chakrabarti, Ranjan [1 ]
机构
[1] Dr Reddys Labs Ltd, Metab Disorders Grp, Discovery Res, Hyderabad 500049, Andhra Pradesh, India
关键词
PPAR; diabetes; synthesis; ethyl 3-(4-aminophenyl)-2-ethoxypropionate; dyslipidemia and plasma glucose;
D O I
暂无
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The design, synthesis and evaluation of several dual PPAR alpha/gamma agonists with three different heterocycles, viz. pyrazolo[4,3-d]pyrimidin-7-one, quinazolin-4-one and benzo[e][1,3]oxazine-4-one for the treatment of type 2 diabetes and associated dyslipidemia are described. Among them, compound 5cb was found to possess a potent dual PPAR alpha/gamma agonist property. It significantly reversed diabetic hyperglycemia while improving overall lipid homeostasis in preclinical animal models.
引用
收藏
页码:27 / 32
页数:6
相关论文
共 50 条
  • [1] Peroxisome proliferator-activated receptor α/γ dual Agonists for the treatment of type 2 diabetes
    Henke, BR
    JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (17) : 4118 - 4127
  • [2] Discovery of a novel series of peroxisome proliferator-activated receptor α/γ dual agonists for the treatment of type 2 diabetes and dyslipidemia
    Liu, K
    Xu, LB
    Berger, JP
    MacNaul, KL
    Zhou, GC
    Doebber, TW
    Forrest, MJ
    Moller, DE
    Jones, AB
    JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (07) : 2262 - 2265
  • [3] Discovery, design, and synthesis of peroxisome proliferator-activated receptor δ agonists
    Chin, Jungwook
    Lee, Geumwoo
    Hwang, Hoosang
    Kang, Heonjoong
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2016, 251
  • [4] Design and synthesis of novel peroxisome proliferator-activated receptor δ agonists
    Jung, Kyungjin
    Kim, Kyung-Hee
    Cho, Sung Jin
    Chin, Jungwook
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2018, 255
  • [5] Peroxisome proliferator-activated receptor (PPAR)γ agonists for diabetes
    Moller, DE
    Greene, DA
    ADVANCES IN PROTEIN CHEMISTRY, VOL 56: DRUG DISCOVERY AND DESIGN, 2001, 56 : 181 - +
  • [6] Peroxisome proliferator-activated receptor agonists
    Willson, TM
    Wahli, W
    CURRENT OPINION IN CHEMICAL BIOLOGY, 1997, 1 (02) : 235 - 241
  • [7] Inflammation in diabetes mellitus:: Role of peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-γ agonists
    Libby, Peter
    Plutzky, Jorge
    AMERICAN JOURNAL OF CARDIOLOGY, 2007, 99 (4A): : 27B - 40B
  • [8] Design, synthesis, and evaluation of potent novel peroxisome proliferator-activated receptor γ indole partial agonists
    Eeda, Venkateswararao
    Wu, Dan
    Lim, Hui-Ying
    Wang, Weidong
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 29 (22)
  • [9] Design and synthesis of benzoxazole containing indole analogs as peroxisome proliferator-activated receptor-γ/δ dual agonists
    Gim, Hyo Jin
    Cheon, Ye-Jin
    Ryu, Jae-Ha
    Jeon, Raok
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (10) : 3057 - 3061
  • [10] Design and synthesis of substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor α/δ dual agonists
    Kasuga, J
    Makishima, M
    Hashimoto, Y
    Miyachi, H
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (03) : 554 - 558