1.
Future Med Chem
; 2(2): 203-13, 2010 Feb.
Artículo
en Inglés
| MEDLINE
| ID: mdl-21426187
RESUMEN
BACKGROUND: The pyrazolyl ketone motif of RO3201195, which exhibits good oral bioavailability and high selectivity for p38 MAPK over other kinases, is a key pharmacophore that could find application in the treatment of Werner syndrome. RESULTS AND DISCUSSION: Microwave irradiation promotes Knoevenagel condensation of a ß-ketonitrile and formamidine, to give ß-aminovinyl ketones, and their subsequent cyclocondensation with a subset of hydrazines to provide rapid access to a 24-membered library of pyrazolyl ketones. The library was evaluated in human hTERT-immortalized HCA2 dermal cells and Werner syndrome cells. CONCLUSION: Four compounds display comparable, if not slightly improved, potency over RO3201195.