2 research outputs found
Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3‑Kinase δ for the Treatment of Respiratory Disease
No full textOptimization
of lead compound <b>1</b>, through extensive
use of structure-based design and a focus on PI3Kδ potency,
isoform selectivity, and inhaled PK properties, led to the discovery
of clinical candidates <b>2</b> (GSK2269557) and <b>3</b> (GSK2292767) for the treatment of respiratory indications via inhalation.
Compounds <b>2</b> and <b>3</b> are both highly selective
for PI3Kδ over the closely related isoforms and are active in
a disease relevant brown Norway rat acute OVA model of Th2-driven
lung inflammation
Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3‑Kinase δ for the Treatment of Respiratory Disease
No full textOptimization
of lead compound <b>1</b>, through extensive
use of structure-based design and a focus on PI3Kδ potency,
isoform selectivity, and inhaled PK properties, led to the discovery
of clinical candidates <b>2</b> (GSK2269557) and <b>3</b> (GSK2292767) for the treatment of respiratory indications via inhalation.
Compounds <b>2</b> and <b>3</b> are both highly selective
for PI3Kδ over the closely related isoforms and are active in
a disease relevant brown Norway rat acute OVA model of Th2-driven
lung inflammation
