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  • Title: Discovery of Highly Isoform Selective Thiazolopiperidine Inhibitors of Phosphoinositide 3-Kinase γ.
    Author: Collier PN, Messersmith D, Le Tiran A, Bandarage UK, Boucher C, Come J, Cottrell KM, Damagnez V, Doran JD, Griffith JP, Khare-Pandit S, Krueger EB, Ledeboer MW, Ledford B, Liao Y, Mahajan S, Moody CS, Roday S, Wang T, Xu J, Aronov AM.
    Journal: J Med Chem; 2015 Jul 23; 58(14):5684-8. PubMed ID: 26121481.
    Abstract:
    A series of high affinity second-generation thiazolopiperidine inhibitors of PI3Kγ were designed based on some general observations around lipid kinase structure. Optimization of the alkylimidazole group led to inhibitors with higher levels of PI3Kγ selectivity. Additional insights into PI3K isoform selectivity related to sequence differences in a known distal hydrophobic pocket are also described.
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