2. Academic Validation
  3. Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors

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

  • J Med Chem. 2018 Jun 28;61(12):5435-5441. doi: 10.1021/acs.jmedchem.8b00447.
Nils Pemberton,  Mickael Mogemark,  Susanne Arlbrandt,  Peter Bold,  Rhona J Cox,  Cristina Gardelli,  Neil S Holden,  Kostas Karabelas,  Johan Karlsson,  Sarah Lever,  Xueshan Li 1,  Helena Lindmark,  Monica Norberg,  Matthew W D Perry,  Jens Petersen,  Sandra Rodrigo Blomqvist,  Matthew Thomas,  Christian Tyrchan,  Annika Westin Eriksson,  Pavol Zlatoidsky,  Linda Öster
Affiliations

Affiliation

  • 1 Pharmaron Beijing Co., Ltd. , No. 6 Taihe Road, BDA , Beijing 100176 , P. R. China.
PMID: 29852070 DOI: 10.1021/acs.jmedchem.8b00447
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.

Figures
Products