| Autor: |
Pemberton N, Mogemark M, Arlbrandt S, Bold P, Cox RJ, Gardelli C, Holden NS, Karabelas K, Karlsson J, Lever S, Li X; Pharmaron Beijing Co., Ltd. , No. 6 Taihe Road, BDA , Beijing 100176 , P. R. China., Lindmark H, Norberg M, Perry MWD, Petersen J, Rodrigo Blomqvist S, Thomas M, Tyrchan C, Westin Eriksson A, Zlatoidsky P, Öster L |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2018 Jun 28; Vol. 61 (12), pp. 5435-5441. Date of Electronic Publication: 2018 Jun 18. |
| DOI: |
10.1021/acs.jmedchem.8b00447 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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