TABLE 1.

Microsomal stability, FabI inhibitory activity, and cLogP values (calculated by ACD/ChemSketch software) of FabI inhibitors with N-benzyl-benzimidazole scaffold

							FabI Inhibitiona	Microsomal Stability
Compd	R1	R2	R3	R4	R5	cLogP	IC50 (μM)	t1/2 (min)	CLint, app (μl/min/mg)
1	H	H	H	H	3′-H, 4′-H, 5′-H, 6′-H, 7′-H	3.24	>100	5.8	240
2	H	H	H	H	3′-H, 4′-H, 5′-CH3, 6′-H, 7′-H	3.70	90	5.4	255
3	H	H	H	H	3′-H, 4′-H, 5′-OCH3, 6′-H, 7′-H	3.16	38	5.6	248
4	H	H	H	H	3′-H, 4′-H, 5′-Br, 6′-H, 7′-H	4.01	27	7.4	186
5	H	H	H	H	3′-H, 4′-Cl, 5′-Cl, 6′-H, 7′-H	4.31	4.7	4.6	304
6	H	H	H	=O	3′-H, 4′-H, 5′-Cl, 6′-H, 7′-H	3.57	>100	N.A.b	N.A.
7	NH2	H	H	H	3′-H, 4′-H, 5′-Cl, 6′-H, 7′-H	3.35	>100	32.5	43
8	COCH3	H	H	H	3′-H, 4′-H, 5′-Cl, 6′-H, 7′-H	3.68	>100	3.8	365
9	NHCOCH3	H	H	H	3′-H, 4′-H, 5′-Cl, 6′-H, 7′-H	3.50	>100	20.3	68
10	CH3	H	H	H	3′-H, 4′-Cl, 5′-Cl, 6′-H, 7′-H	4.83	3.2	4.3	324
11	SCH2CH3	H	H	H	3′-H, 4′-H, 5′-Cl, 6′-H, 7′-H	5.63	>100	3.1	452
12	H	CH3	CH3	=O	3′-H, 4′-H, 5′-H, 6′-Cl, 7′-H	4.53	>100	N.A.	N.A.
13	H	CH3	CH3	CH3	3′-H, 4′-H, 5′-Cl, 6′-Cl, 7′-H	5.57	2.75	9.2	151
14	H	CH3	CH3	H	3′-H, 4′-H, 5′-Cl, 6′-H, 7′-H	4.76	0.3	3.8	369
15	H	CH3	CH3	H	3′-Cl, 4′-H, 5′-Cl, 6′-H, 7′-H	5.36	0.7	4.0	345
16	H	CH3	CH3	H	3′-H, 4′-H, 5′-Cl, 6′-Cl, 7′-H	5.23	0.3	5.3	263
17	H	CH3	CH3	H	3′-H, 4′-OCH3, 5′-Cl, 6′-H, 7′-H	4.62	>100	2.4	573
18	H	CH3	CH3	H	3′-H, 4′-OCH3, 5′-Cl, 6′-H, 7′-Br	5.60	>100	3.5	395
19	H	CH3	CH3	H	3′-H, 4′-H, 5′-OCH3, 6′-H, 7′-H	4.08	0.5c	<2	>693
20	H	CH3	CH3	H	3′-H, 4′, 5′-OCH2O, 6′-H, 7′-H	4.02	1.0c	3.7	376
21	H	CH3	CH3	H	3′-H, 4′-CH3, 5′-OCH3, 6′-H, 7′-H	4.54	0.25c	<2	>693
22	H	CH3	CH3	H	3′-H, 4′-CH3, 5′-OH, 6′-H, 7′-H	3.88	1.3	3.3	426

^aFabI IC₅₀ values determined per published procedures (Hevener et al. 2012);

^bN.A., not available;

^cIC₅₀ value determined with reduced FabI concentration of 10 nM.