. 2014 Dec 4;6(3):276–281. doi: 10.1021/ml500420y

Table 1. Structure–Activity Relationships of Phenyl- and Benzylsulfonamide Matched Pairs^a.

graphic file with name ml-2014-00420y_0005.jpg

Compd	n	R	RORc IC₅₀^b (μM)	RORc SRC1 EC₅₀^c (μM) [% efficacy]	cLogP^d	LLE^e	MOA^f
3	0	H	0.25	0.069 [+35%]	3.7	3.5	Agonist
4	1	H	0.015	0.011 [−99%]	3.3	4.7	Inverse Agonist
9	2	H	0.11	0.31 [−64%]	3.7	2.8	Inverse Agonist
10	0	2-F	0.076	0.063 [+46%]	3.9	3.3	Agonist
11	1	2-F	0.010	0.003 [−98%]	3.4	5.1	Inverse Agonist
12	0	3-F	0.065	0.041 [+46%]	3.9	3.5	Agonist
13	1	3-F	0.025	0.010 [−98%]	3.5	4.5	Inverse Agonist
14	0	4-F	0.22	>10 [−37%]	3.9	-	Inverse Agonist
15	1	4-F	0.017	0.007 [−97%]	3.5	4.7	Inverse Agonist
16	0	2-Cl	0.055	0.047 [+33%]	4.4	2.9	Agonist
17	1	2-Cl	0.009	0.004 [−96]	3.9	4.5	Inverse Agonist
18	0	3-Cl	0.022	0.050 [+53%]	4.4	2.9	Agonist
19	1	3-Cl	0.019	0.009 [−98%]	4.1	4.0	Inverse Agonist
20	0	4-Cl	0.092	0.19 [−63%]	4.4	2.3	Inverse Agonist
21	1	4-Cl	0.037	0.033 [−97%]	4.1	3.4	Inverse Agonist
22	0	3,5-diCl	0.006	0.006 [+65%]	5.1	3.4	Agonist
23	1	3,5-diCl	0.029	0.040 [−92%]	4.8	2.6	Inverse Agonist
24	0	3,5-diF	0.049	0.014 [+43%]	4.1	3.7	Agonist
25	0	3-OMe	0.036	0.026 [+54%]	3.8	3.8	Agonist

All assay results are reported as the geometric mean of at least two separate runs.²⁴

Biochemical inhibition of the RORc-LBD and [³H₂]25-hydroxycholesterol interaction.

Activation or inhibition of RORc-LBD recruitment of the SRC1 coactivator; positive “%eff.” denotes agonism and negative “%eff.” denotes inverse agonism relative to the basal assay signal for apo-RORc LBD in this assay format.

Calculated logP (cLogP) value.²⁷

Ligand-lipophilicity efficiency (LLE)²⁵ was calculated using RORc SRC1 EC₅₀ and the cLogP.

Mechanism of action (MOA) reported as agonist, inverse agonist, or silent ligand.

Table 1. Structure–Activity Relationships of Phenyl- and Benzylsulfonamide Matched Pairsa.

Table 1. Structure–Activity Relationships of Phenyl- and Benzylsulfonamide Matched Pairs^a.