Strategic use of conformational bias and structure based design to identify potent JAK3 inhibitors with improved selectivity against the JAK family and the kinome.
Bioorg Med Chem Lett
; 23(9): 2793-800, 2013 May 01.
Article
en En
| MEDLINE
| ID: mdl-23540648
Using a structure based design approach we have identified a series of indazole substituted pyrrolopyrazines, which are potent inhibitors of JAK3. Intramolecular electronic repulsion was used as a strategy to induce a strong conformational bias within the ligand. Compounds bearing this conformation participated in a favorable hydrophobic interaction with a cysteine residue in the JAK3 binding pocket, which imparted high selectivity versus the kinome and improved selectivity within the JAK family.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
/
Inhibidores de Proteínas Quinasas
/
Janus Quinasa 3
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos