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Issue 1, 2013
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Optimisation of biphenyl acetic acid inhibitors of diacylglycerol acetyl transferase 1 – the discovery of AZD2353

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Abstract

Inhibition of diacylglycerol acetyl transferase 1 is of great interest in the treatment of diabetes, obesity and other diseases that constitute the metabolic syndrome. Small molecule inhibitors of the enzyme are often dogged with physicochemical property-related problems such as poor solubility. Herein, the optimisation of a series of biphenyl acetic acid inhibitors is reported. Focus on ligand efficiency and ligand lipophilicity efficiency and a strategy based on conformational restriction led to compounds with excellent potency and ADMET properties, culminating in the discovery of AZD2353.

Graphical abstract: Optimisation of biphenyl acetic acid inhibitors of diacylglycerol acetyl transferase 1 – the discovery of AZD2353

  • This article is part of the themed collection: New Talent
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Publication details

The article was received on 11 Jul 2012, accepted on 26 Sep 2012 and first published on 25 Oct 2012


Article type: Concise Article
DOI: 10.1039/C2MD20190A
Citation: Med. Chem. Commun., 2013,4, 159-164
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    Optimisation of biphenyl acetic acid inhibitors of diacylglycerol acetyl transferase 1 – the discovery of AZD2353

    M. J. Waring, A. M. Birch, S. Birtles, L. K. Buckett, R. J. Butlin, L. Campbell, P. M. Gutierrez, P. D. Kemmitt, A. G. Leach, P. A. MacFaul, C. O'Donnell and A. V. Turnbull, Med. Chem. Commun., 2013, 4, 159
    DOI: 10.1039/C2MD20190A

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