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Citation: Jing Huang, Bin Guo, Wen-Jing Chu, Xin Xie, Yu-She Yang, Xian-Li Zhou. Design, synthesis and evaluation of potent G-protein coupled receptor 40 agonists[J]. Chinese Chemical Letters, ;2016, 27(01): 159-162. doi: 10.1016/j.cclet.2015.09.002 shu

Design, synthesis and evaluation of potent G-protein coupled receptor 40 agonists

  • 1.

    a School of Life Science and Engineering, Southwest Jiao Tong University, Chengdu 610031, China;

  • 2.

    b State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;

  • 3.

    c CAS Key Laboratory of Receptor Research, The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

  • Corresponding author: Yu-She Yang,  Xian-Li Zhou, 
  • Received Date: 11 February 2015
    Available Online: 10 May 2015

    Fund Project: This work was supported by grants from the National Natural Science Foundation of China(No. 2140222). (No. 2140222)

  • GPR40 has emerged as an attractive drug target for the treatment of type 2 diabetes due to its role in the enhancement of insulin secretion with glucose dependency. With the aim to improve the metabolic and safety profiles, a series of novel phenylpropionic acid derivatives were synthesized. Extensive structural optimization led to identification of compounds 22g and 23e as potent GPR40 agonists with moderate liver microsomal stability. All the discovery supported further exploration surrounding this scaffold.
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    1. [1]

      [1] S. Wild, G. Roglic, A. Green, R. Sicree, H. King, Global prevalence of diabetes:estimates for the year 2000 and projections for 2030, Diabetes Care 27(2004) 1047-1053.

    2. [2]

      [2] B. Ahrén, Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes, Nat. Rev. Drug Discov. 8(2009) 369-385.

    3. [3]

      [3] S. Edfalk, P. Steneberg, H. Edlund, Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion, Diabetes 57(2008) 2280-2287.

    4. [4]

      [4] A.D. Mancini, V. Poitout, The fatty acid receptor FFA1/GPR40 a decade later:how much do we know? Trends Endocrinol. Metab. 24(2013) 398-407.

    5. [5]

      [5] N.G. Morgan, S. Dhayal, G-protein coupled receptors mediating long chain fatty acid signalling in the pancreatic beta-cell, Biochem. Pharmacol. 78(2009) 1419-1427.

    6. [6]

      [6] E. Defossa, M. Wagner, Recent developments in the discovery of FFA1 receptor agonists as novel oral treatment for type 2 diabetes mellitus, Bioorg. Med. Chem. Lett. 24(2014) 2991-3000.

    7. [7]

      [7] R. Takano, M. Yoshida, M. Inoue, et al., Discovery of DS-1558:a potent and orally bioavailable GPR40 agonist, ACS Med. Chem. Lett. 6(2015) 266-270.

    8. [8]

      [8] E. Christiansen, M.E. Due-Hansen, C. Urban, et al., Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability, J. Med. Chem. 56(2013) 982-992.

    9. [9]

      [9] J.B. Houze, L.S. Zhu, Y. Sun, et al., AMG 837:a potent, orally bioavailable GPR40 agonist, Bioorg. Med. Chem. Lett. 22(2012) 1267-1270.

    10. [10]

      [10] N. Negoro, S. Sasaki, M. Ito, et al., Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that act as G protein-coupled receptor 40/free fatty acid receptor 1 agonists, J. Med. Chem. 55(2012) 1538-1552.

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