Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 58, Issue 18, Pages 7381-7399Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b00767
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Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3K delta potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (G5K2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3K delta over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.
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