Imidazopyridine-Based Inhibitors of Glycogen Synthase Kinase 3: Synthesis and Evaluation of Amide Isostere Replacements of the Carboxamide Scaffold

Authors

  • Ulrika Yngve,

    1. Medicinal Chemistry, iScience, CNSP iMed, AstraZeneca R&D Södertälje, SE-151 85 Södertälje
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  • Peter Söderman,

    1. Medicinal Chemistry, iScience, CNSP iMed, AstraZeneca R&D Södertälje, SE-151 85 Södertälje
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  • Mats Svensson,

    1. Medicinal Chemistry, iScience, CNSP iMed, AstraZeneca R&D Södertälje, SE-151 85 Södertälje
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  • Susanne Rosqvist,

    1. Neuroscience, iScience, CNSP iMed, AstraZeneca R&D Södertälje, SE-151 85 Södertälje
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  • Per I. Arvidsson

    Corresponding author
    1. Project Management, CNSP iMed, AstraZeneca R&D Södertälje, SE-151 85 Södertälje, (phone: +46-8-553 259 23; fax: +46-8-553 288 77)
    2. Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala
    3. School of Pharmacy and Pharmacology, Westville Campus, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa
    • School of Pharmacy and Pharmacology, Westville Campus, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa
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Abstract

In this study, we explored the effect of bioisostere replacement in a series of glycogen synthase kinase 3 (GSK3) inhibitors based on the imidazopyridine core. The synthesis and biological evaluation of a number of novel sulfonamide, 1,2,4-oxadiazole, and thiazole derivates as amide bioisosteres, as well as a computational rationalization of the obtained results are reported.

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