Details

Autor(en) / Beteiligte

• Pemberton, Nils
• Mogemark, Mickael
• Arlbrandt, Susanne
• Bold, Peter
• Cox, Rhona J
• Gardelli, Cristina
• Holden, Neil S
• Karabelas, Kostas
• Karlsson, Johan
• Lever, Sarah
• Li, Xueshan
• Lindmark, Helena
• Norberg, Monica
• Perry, Matthew W. D
• Petersen, Jens
• Rodrigo Blomqvist, Sandra
• Thomas, Matthew
• Tyrchan, Christian
• Westin Eriksson, Annika
• Zlatoidsky, Pavol
• Öster, Linda

Titel

Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3‑Kinase (PI3K)‑γ Inhibitors

Ist Teil von

• Journal of medicinal chemistry, 2018-06, Vol.61 (12), p.5435-5441

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.