Table 4.

TLR signaling inhibition by C3 BSC pyrazoles with methoxy substituents.

Cmpd	R1	R5	IC50 (μM)
			TLR9	TLR7	TLR2	TLR4	Tox.
37	p-OMe	p-OMe	4.26 ± 0.04	> 50	28.4 ± 0.1	n.d.	28.2 ± 2.8
38	H	p-OMe	4.44 ± 0.36	4.96 ± 0.33	28.6 ± 0.1	n.d.	15.8 ± 2.9
39	m-OMe	p-OMe	5.75 ± 0.23	12.3 ± 0.1	11.6 ± 0.3	n.d.	14.0 ± 2.8
40	p-Me	p-OMe	3.95 ± 0.11	11.3 ± 0.1	24.3 ± 0.6	17.7 ± 0.7	13.3 ± 2.5
41	p-OCF3	p-OMe	5.81 ± 0.55	12.1 ± 0.5	16.0 ± 0.1	19.1 ± 0.4	16.6 ± 2.3
42	p-Cl	p-OMe	4.49 ± 0.69	34.7 ± 2.4	16.0 ± 0.1	n.d.	20.0 ± 5.1
43	p-NO2	p-OMe	3.02 ± 0.11	22.3 ± 0.9	26.5 ± 1.6	26.6 ± 0.3	31.4 ± 3.1
44	4-NHBoc	p-OMe	3.00 ± 0.24	> 50	> 50	> 50	> 50
45	4-NH2	p-OMe	4.08 ± 0.38	19.6 ± 0.8	13.1 ± 1.0	19.3 ± 1.7	15.8 ± 1.4
46	p-OMe	H	4.61 ± 0.23	> 50	27.4 ± 0.6	n.d.	22.6 ± 3.5
47	p-OMe	2,4-(OMe)2	3.73 ± 0.11	3.51 ± 0.07	15.5 ± 0.8	13.5 ± 0.7	8.61 ± 1.91
48	p-OMe	4-NH C(O)Me	1.24 ± 0.07	3.19 ± 0.08	5.18 ± 0.48	5.60 ± 0.34	10.7 ± 0.8
49	p-OMe	3,4,5- (OMe)3	3.60 ± 0.49	3.14 ± 0.63	3.79 ± 1.10	1.26 ± 0.39	14.7 ± 0.1
50	p-OMe	3,4- (OMe)2	3.03 ± 0.38	17.0 ± 1.1	17.9 ± 0.7	13.5 ± 0.6	10.1 ± 2.1
51	p-OMe	3-Cl- 4-OMe	6.00 ± 0.04	7.30 ± 0.33	> 50	> 50	18.1 ± 1.2
52	p-OMe	3,5-(CH3)2- 4-OMe	7.53 ± 0.49	8.42 ± 0.55	> 50	> 50	17.1 ± 1. 4

n.d. = not determined