Table 1.

Initial Optimization of Lead Compound 1

Compd	X	R	PARP-1 IC50 (nM)a	pIC50 ± S.D (nM)	PARP-2 IC50 (nM)a	pIC50 ± S.D (nM)
1	H	-H	434	6.41 ± 0.20	NT	-
48	H		>50 (2%b)	-	NT	-
49	H		>50 (7%)	-	NT	-
50	H		>50 (5%)	-	NT	-
51	H		35	7.50 ± 0.20	2.1	8.69 ± 0.01
52	H		>50 (4%)	-	NT	-
53	3-	-H	>50 (14%)	-	<50 (76% c)	-
54	H		>50 (7%)	-	NT	-
55	H		>50 (10%)	-	NT	-
56	H		>50 (19%)	-	<50 (56%)	-
57	3-F		56	7.28 ± 0.14	<50 (100%)	-
58	2-OCH3		47	7.33 ± 0.07	1.6	8.80 ± 0.05
59	H		>50 (4%)	-	NT	-
60	H	-COOH	68	7.17 ± 0.08	NT	-
Olad	-	-	1.2	8.93 ± 0.07	0.5	9.40 ± 0.30
Vele	-	-	1.5	8.83 ± 0.06	100% @ 10 nM	-

^aData shown are mean values obtained from two independent experiments performed in duplicates.

^b% inhibition screening at a single concentration (50 nM unless otherwise specified) was performed in duplicates and data shown is an average of two independent experiments;

^c% inhibition screening of PARP-2, was performed at 50 nM concentration, in duplicates by one experiment;

^dOlaparib;

^eVeliparib;

Not tested (NT).