Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2-P4 linkers.
Bioorg Med Chem Lett
; 22(23): 7207-13, 2012 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-23084906
ABSTRACT
A series of macrocyclic compounds containing a cyclic constraint in the P2-P4 linker region have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155K, A156T, A156V, and D168V mutant activity while maintaining high rat liver exposure. The effect of the constraint is most dramatic against gt 1b A156 mutants where ~20-fold improvements in potency are achieved by introduction of a variety of ring systems into the P2-P4 linker.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protease Inhibitors
/
Carrier Proteins
/
Viral Nonstructural Proteins
/
Hepacivirus
/
Macrocyclic Compounds
Limits:
Animals
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2012
Document type:
Article
Affiliation country:
United States