Philip 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,
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.
Tópico(s): Protein Kinase Regulation and GTPase Signaling
2015 - American Chemical Society | Journal of Medicinal Chemistry