Table 2. Inhibition of the S100A10 Interaction with Annexin A2 by 5-Substituted 3-Hydroxy-1-(2-hydroxypropyl)-4-(4-methylbenzoyl)-1H-pyrrol-2(5H)-ones and Activity in Counterscreen Assay.

						annexin−S100A10 interaction		counterscreen
no.	type	R2	R3	R4	R5	pIC50a	IC50 (μM)	% controlb
P						5.99 ± 0.10	1
1a	I	H	H	iPr	H	4.85 ± 0.09	14	101 ± 7
13	II					<3	>1000
14	III					3.89 ± 0.15*	128
15	I	H	H	H	H	3.60 ± 0.33*	251
16	I	H	iPr	H	H	4.94 ± 0.14	11	100 ± 16
17	I	H	H	Me	H	4.07 ± 0.10*	85
18	I	H	H	Et	H	4.80 ± 0.25	16
19	I	H	H	nPr	H	4.74 ± 0.09	18	97 ± 9
20	I	H	H	tBu	H	4.55 ± 0.05**	28	123 ± 7
21	I	H	H	NMe2	H	3.56 ± 0.55*	275
22	I	H	H	OH	H	<3	>1000
23	I	H	H	OCF3	H	5.02 ± 0.11	9	110 ± 8
24	I	H	H	CF3	H	5.20 ± 0.36	6	102 ± 1
25	I	H	CF3	H	H	5.08 ± 0.09	8	110 ± 6
26	I	CF3	H	CF3	H	5.12 ± 0.09	8	102 ± 6
27	I	H	CF3	H	CF3	5.41 ± 0.12	4	109 ± 3
28	I	H	H	Cl	H	3.93 ± 0.21*	117
29	I	H	Cl	H	H	3.98 ± 0.15*	105
30	I	H	Cl	H	Cl	5.16 ± 0.15	7	119 ± 4
31	I	H	CF3	Cl	H	5.12 ± 0.06	8	121 ± 11

^aData were expressed as % of the specific signal of the nontreated control and analyzed by nonlinear regression using Graphpad Prism. pIC₅₀ ± standard error of the fit (n = 4−8 data points per concentration, 0.4−100 μM). The midpoint of the dose−response curve is given based on a floating fit unless indicated as follows: *, bottom fixed at zero; **, bottom fixed at zero, top fixed at 100%.

^bPercent remaining signal at 50 μM compound relative to diluent only (mean ± standard error mean of >3 determinations). P = nonlabeled synthetic annexin N terminus peptide.