Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease.
J Med Chem
; 58(18): 7381-99, 2015 Sep 24.
Article
em En
| MEDLINE
| ID: mdl-26301626
ABSTRACT
Optimization of lead compound 1, 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 2 (GSK2269557) and 3 (GSK2292767) for the treatment of respiratory indications via inhalation. Compounds 2 and 3 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxazóis
/
Doenças Respiratórias
/
Sulfonamidas
/
Inibidores de Fosfoinositídeo-3 Quinase
/
Indazóis
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Med Chem
Ano de publicação:
2015
Tipo de documento:
Article