1.
Bioorg Med Chem Lett
; 21(21): 6586-90, 2011 Nov 01.
Artigo
em Inglês
| MEDLINE
| ID: mdl-21925880
RESUMO
We report the use of fragment screening and fragment based drug design to develop a PI3γ kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed into potent and ligand efficient lead compounds using structure guided fragment growing and merging strategies. This led to a potent, selective, and cell permeable PI3γ kinase inhibitor with good metabolic stability that was useful as a preclinical tool compound.