Abstract
A series of novel pyrrolocarbazoles was synthesized as potential PARP-1 inhibitors. Pyrrolocarbazole 1 was identified as a potent PARP-1 inhibitor (IC50 = 36 nM) from our internal database. Synthesis of analogs around this template with the aid of modeling studies led to the identification of the truncated imide 14. Compound 14 (IC50 = 40 nM), with deleted B-ring, was found to be an equipotent PARP-1 inhibitor.
MeSH terms
-
Carbazoles / chemical synthesis*
-
Carbazoles / chemistry
-
Carbazoles / pharmacology*
-
Crystallography, X-Ray
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology*
-
Humans
-
Models, Molecular
-
Molecular Structure
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerase Inhibitors*
-
Structure-Activity Relationship
Substances
-
Carbazoles
-
Enzyme Inhibitors
-
Poly(ADP-ribose) Polymerase Inhibitors
-
PARP1 protein, human
-
Poly (ADP-Ribose) Polymerase-1