Table 1.

Inhibitory activities for compounds 1–16^a

	R1	R2	R3	R4	R5	AKR1C1 inhibitionb,c(%)	AKR1C2 inhibitionb,c(%)	AKR1C3 inhibitionb,c(%)	AKR1C4 inhibitionc(%)
1	OH	H	H	NO2	H	NI	31.6d	1.9	n.d.
2	Cl	H	H	NO2	H	NI	23.4	3.4	n.d.
3	OMe	OMe	H	NO2	H	22.2	NI	3.5	n.d.
4	Cl	H	Me	NO2	H	NI	22.5	NI	n.d.
5	H	H	H	NH2	H	8.0	NI	NI	n.d.
6	OMe	OMe	H	NH2	H	18.0	20.2	5.6	n.d.
7	OH	H	H	NH2	H	9.7	28.7	5.6	n.d.
8	Br	H	H	NO2	F	53.2	33.6	5.6	n.d.
						IC50 = 8.4 µM	IC50 = 15.6 µM
9	H	H	H	OH	H	NI	NI	42.1	n.d.
								IC50 = 12.7 µM
						IC50 = >100 µMc (>19)e	IC50 = 48.1 µMc (9)e	IC50 = 5.19 µMc	IC50 = 100 µMc (>19)e
10	Cl	H	H	OH	H	17.4	6.7	77.8	n.d.
								IC50 = 2.2 µM
						IC50 = 50.8 µMc (164)e	IC50 = 50.2 µMc (162)e	IC50 = 0.31 µMc	IC50 = 20.1 µMc (65)e
11	OMe	OMe	H	OH	H	11.8	29.4	70.2 IC50 = 5.2 µM	n.d.
						IC50 = 86.3 µMcc (30)e	IC50 = 30.0 µMc (10)e	IC50 = 2.9 µMc	IC50 = 50.9 µMc (18)e
12	NO2	H	H	OH	H	11.8	10.4	87.9 IC50 = 2.6 µM	n.d.
						IC50 = 35.2 µMc (42)e	IC50 = 41.6 µMc (50)e	IC50 = 0.84 µMc	IC50 = 32.3 µMc (38)e
13	Br	H	H	OH	H	21.6	16.7	89.6	n.d.
								IC50 = 1.9 µM
						IC50 = ~100 µMc (286)	IC50 = 63.0 µMc (180)e	IC50 = 0.35 µMc	IC50 = 30.3 µMc (86)e
14	Br	H	H	OEt	H	31.9	36.8	19.1	n.d.
						IC50 = 20.6 µM	IC50 = 17.1 µM
15	Br	H	H	OBu	H	65.9	70.5	30.4	n.d.
						IC50 = 4.9 µM	IC50 = 4.9 µM
16	H	H	H	OBu	NO2	70.8	58.3	47.2	n.d.
						IC50 = 3.2 µM	IC50 = 6.5 µM	IC50 = 7.5 µM

NI, No inhibition observed.

n.d., Not determined.

^aThe data represent the mean value of two independent experiments. Standard deviations were within ±10% of these mean values.

^bThe inhibitory activities at 10 µM of each compound and IC₅₀ values were determined with the primary assay, first line.

^cThe IC₅₀ values of the selected 5 compounds were determined with the secondary assay, second line.

^dThe compound precipitated at higher concentrations under assay conditions.

^eValues in parenthesis, determined on the basis of the secondary assay results, represent fold selectivity for AKR1C3.