Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors.
Bioorg Med Chem Lett
; 23(9): 2743-9, 2013 May 01.
Article
in En
| MEDLINE
| ID: mdl-23522834
ABSTRACT
Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson's disease and this Letter describes the SAR of a series of dihydropteridinone based Plk-2 inhibitors. By optimizing both the N-8 substituent and the biaryl region of the inhibitors we obtained single digit nanomolar compounds such as 37 with excellent selectivity for Plk-2 over Plk-1. When dosed orally in rats, compound 37 demonstrated a 41-45% reduction of pS129-α-synuclein levels in the cerebral cortex.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Design
/
Protein Serine-Threonine Kinases
/
Protein Kinase Inhibitors
Limits:
Animals
/
Humans
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2013
Document type:
Article
Affiliation country:
Estados Unidos