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
  • [21] Design and Synthesis of Highly Active Peroxisome Proliferator-Activated Receptor (PPAR) / Inverse Agonists with Prolonged Cellular Activity
    Toth, Philipp M.
    Lieber, Sonja
    Scheer, Frithjof M.
    Schumann, Tim
    Schober, Yvonne
    Nockher, Wolfgang A.
    Adhikary, Till
    Mueller-Bruesselbach, Sabine
    Mueller, Rolf
    Diederich, Wibke E.
    CHEMMEDCHEM, 2016, 11 (05) : 488 - 496
  • [22] Effects of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus
    Bajaj, M.
    Suraamornkul, S.
    Hardies, L. J.
    Glass, L.
    Musi, N.
    DeFronzo, R. A.
    DIABETOLOGIA, 2007, 50 (08) : 1723 - 1731
  • [23] Peroxisome proliferator-activated receptor (PPAR) modulators: Diabetes and beyond
    Jones, AB
    MEDICINAL RESEARCH REVIEWS, 2001, 21 (06) : 540 - 552
  • [24] Enantioselective Synthesis of PPAR (Peroxisome Proliferator-Activated Receptors) Agonists and Antagonists
    Goya, Pilar
    Perez-Fernandez, Ruth
    Gonzalez-Muniz, Rosario
    Elguero, Jose
    CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2014, 14 (10) : 1283 - 1293
  • [25] Neuroprotective mechanisms of peroxisome proliferator-activated receptor agonists in Alzheimer’s disease
    Rupinder K. Sodhi
    Nirmal Singh
    Amteshwar S. Jaggi
    Naunyn-Schmiedeberg's Archives of Pharmacology, 2011, 384 : 115 - 124
  • [26] Review:: Peroxisome proliferator-activated receptor-γ and its role in the development and treatment of diabetes
    Leff, T
    Mathews, ST
    Camp, HS
    EXPERIMENTAL DIABESITY RESEARCH, 2004, 5 (02) : 99 - 109
  • [27] The use of hepatotoxic signals to predict the safety of peroxisome proliferator-activated receptor agonists
    Hastings, Kenneth L.
    EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2006, 2 (04) : 489 - 492
  • [28] Neuroprotective mechanisms of peroxisome proliferator-activated receptor agonists in Alzheimer's disease
    Sodhi, Rupinder K.
    Singh, Nirmal
    Jaggi, Amteshwar S.
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2011, 384 (02) : 115 - 124
  • [29] Design and Synthesis of Dual Modulators of Soluble Epoxide Hydrolase and Peroxisome Proliferator-Activated Receptors
    Buscato, Estella
    Bloecher, Rene
    Lamers, Christina
    Klingler, Franca-Maria
    Hahn, Steffen
    Steinhilber, Dieter
    Schubert-Zsilavecz, Manfred
    Proschak, Ewgenij
    JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (23) : 10771 - 10775
  • [30] Peroxisome proliferator-activated receptor agonists as potential therapeutic agents in multiple sclerosis
    Niino, Masaaki
    MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2007, 7 (11) : 1129 - 1135