Discovery of Highly Isoform Selective Thiazolopiperidine Inhibitors of Phosphoinositide 3-Kinase γ
2015; American Chemical Society; Volume: 58; Issue: 14 Linguagem: Inglês
10.1021/acs.jmedchem.5b00498
ISSN1520-4804
AutoresPhilip N. Collier, David Messersmith, Arnaud LeTiran, Upul K. Bandarage, Christina Boucher, Jon H. Come, Kevin M. Cottrell, Véronique Damagnez, John Doran, James P. Griffith, Suvarna Khare-Pandit, Elaine Krueger, Mark W. Ledeboer, Brian Ledford, Yusheng Liao, Sudipta Mahajan, Cameron Stuver Moody, Setu Roday, Tiansheng Wang, Jinwang Xu, Alex M. Aronov,
Tópico(s)Protein Kinase Regulation and GTPase Signaling
ResumoA 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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