Table 1.

ERα and ERβ relative binding affinity (RBAs) of compounds 2a–m, 4a–f, 6a–b and 8a–b.^a

2a–h, 4a–f, 6a,b, 8a,b			2i–k		2l,m
entry	cmpd	core	R	ERαb	ERβb	β/α
1	2a		H	0.040 ± 0.004	0.79 ± 0.11	19.8
2	2b		2-Me	1.43 ± 0.19	1.74 ± 0.26	1.2
3	2c		3-Me	0.004 ± 0.001	0.002	0.5
4	2d		3,5-diMe	0.003 ± 0.001	0.005 ± 0.001	1.7
5	2e		2-F	2.03 ± 0.19	33.1 ± 5.8	16
6	2f		2-Cl	6.7 ± 1.3	10.0 ± 2.4	1.5
7	2g		3-F	0.013 ± 0.004	0.142 ± 0.004	11
8	2h		3-Cl	0.009 ± 0.001	0.036	4.0
9	2i		2-F	0.008 ± 0.002	0.066 ± 0.066	8.3
10	2j		3-F	0.009 ± 0.006	0.041 ± 0.004	0.4
11	2k		4-F	~0.001	0.010 ± 0.002	10
12	2l		F	0.97 ± 0.01	0.91 ± 0.26	0.94
13	2m		Cl	4.29 ± 0.64	5.89 ± 0.21	1.4
14	4a		H	0.57 ± 0.12	1.69 ± 0.45	2.9
15	4b		2-Me	2.16 ± 0.54	4.9 ± 1.3	2.25
16	4c		3-Me	0.830	0.297	0.36
17	4d		3,5-diMe	0.039 ± 0.003	0.004 ± 0.001	0.10
18	4e		2-F	3.03 ± 0.85	9.1 ± 2.2	3.0
19	4f		2-Cl	13.07 ± 1.1	17.5 ± 2.1	1.3
20	6a		2-F	1.22 ± 0.32	10.4 ± 1.2	8.5
21	6b		2-Cl	4.21 ± 0.54	25.6 ± 5.7	6.1
22	8a		2-F	1.22 ± 0.35	2.54 ± 0.76	2.1
23	8b		2-Cl	6.50 ± 0.61	7.73 ± 2.1	1.2

^aTo simplify comparisons between compounds in closely related series, we designate locant positions of the substituents on the phenyl groups with respect to the thiophene core; locant positions within the thiophene core itself are given by numbers in italics.

^bRelative binding affinity (RBA) values are determined by competitive radiometric binding assays and are expressed as IC₅₀^estradiol/IC₅₀^compound×100 ± the range or standard deviation (RBA, estradiol = 100%). In these assays, the K_D for estradiol is 0.2 nM on ERα and 0.5 nM on ERβ.⁵¹ For details, see the Experimental Section.