| Literature DB >> 29852070 |
Nils Pemberton, Mickael Mogemark, Susanne Arlbrandt, Peter Bold, Rhona J Cox, Cristina Gardelli, Neil S Holden, Kostas Karabelas, Johan Karlsson, Sarah Lever, Xueshan Li1, Helena Lindmark, Monica Norberg, Matthew W D Perry, Jens Petersen, Sandra Rodrigo Blomqvist, Matthew Thomas, Christian Tyrchan, Annika Westin Eriksson, Pavol Zlatoidsky, Linda Öster.
Abstract
In this paper, we describe the discovery and optimization of a new chemotype of isoform selective PI3Kγ inhibitors. Starting from an HTS hit, potency and physicochemical properties could be improved to give compounds such as 15, which is a potent and remarkably selective PI3Kγ inhibitor with ADME properties suitable for oral administration. Compound 15 was advanced into in vivo studies showing dose-dependent inhibition of LPS-induced airway neutrophilia in rats when administered orally.Entities:
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Year: 2018 PMID： 29852070 DOI： 10.1021/acs.jmedchem.8b00447
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446