| Literature DB >> 26301626 |
Kenneth Down1,2,3, Augustin Amour1,2,3, Ian R Baldwin1,2,3, Anthony W J Cooper1,2,3, Angela M Deakin1,2,3, Leigh M Felton1,2,3, Stephen B Guntrip1,2,3, Charlotte Hardy1,2,3, Zoë A Harrison1,2,3, Katherine L Jones1,2,3, Paul Jones1,2,3, Suzanne E Keeling1,2,3, Joelle Le1,2,3, Stefano Livia1,2,3, Fiona Lucas1,2,3, Christopher J Lunniss1,2,3, Nigel J Parr1,2,3, Ed Robinson1,2,3, Paul Rowland1,2,3, Sarah Smith1,2,3, Daniel A Thomas1,2,3, Giovanni Vitulli1,2,3, Yoshiaki Washio1,2,3, J Nicole Hamblin1,2,3.
Abstract
Optimization of lead compound 1, through extensive use of structure-based design and a focus on PI3Kδ potency, isoform selectivity, and inhaled PK properties, led to the discovery of clinical candidates 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 are both highly selective for PI3Kδ over the closely related isoforms and are active in a disease relevant brown Norway rat acute OVA model of Th2-driven lung inflammation.Entities:
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Year: 2015 PMID： 26301626 DOI： 10.1021/acs.jmedchem.5b00767
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446