Cover Picture: 2-Phenoxy-nicotinamides are Potent Agonists at the Bile Acid Receptor GPBAR1 (TGR5) (ChemMedChem 4/2013)

Authors

  • Dr. Rainer E. Martin,

    Corresponding author
    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
    • Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Dr. Caterina Bissantz,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Olivier Gavelle,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Christoph Kuratli,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Dr. Henrietta Dehmlow,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Dr. Hans G. F. Richter,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Dr. Ulrike Obst Sander,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Dr. Shawn D. Erickson,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche Inc. 340 Kingsland Street, Nutley (USA)
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  • Dr. Kyungjin Kim,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche Inc. 340 Kingsland Street, Nutley (USA)
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  • Dr. Sherrie Lynn Pietranico-Cole,

    1. Small Molecule Research, Medicinal Chemistry, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche Inc. 340 Kingsland Street, Nutley (USA)
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  • Dr. Rubén Alvarez-Sánchez,

    1. Nonclinical Drug Safety, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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  • Dr. Christoph Ullmer

    1. DTA Vascular and Metabolic Diseases, Pharma Research & Early Development (pRED), F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel (Switzerland)
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Abstract

original image

The front cover picture shows a 3D homology model of the human G protein-coupled bile acid receptor (GPBAR1; carbon atoms in green). The full receptor structure is shown (top right) with the proposed binding site of GPBAR1 agonists indicated (red ellipse). The main picture shows a zoom of this binding site into which taurolithocholic acid (TLCA; carbon atoms in cyan) and a 2-phenoxy-nicotinamide agonist (carbon atoms in magenta) are docked. The alignment of TLCA with our advanced lead compounds enabled the identification of the optimal attachment point for a polar vector, which was critical to improve the physicochemical properties of the series. For more details, see the Communication by Rainer E. Martin et al. on p. 569 ff.

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