Table 3.

Spacer structures, maximum lengths, and relative binding affinity (RBA) values of mono- and bivalent OHT ligands (11–20).

Entry	Ligand	Spacer structure	Maximum length a [Å]	Homo-bivalent ligand (Z-Z/Z isomer)		Hetero-bivalent ligand (Z-E/E isomer)
				ERα	ERβ	ERα	ERβ
1.	11	EG1	7.24	13.8 ± 4.3	6.11 ± 1.4	6.60 ± 0.5	3.44 ± 0.7
2.	12	EG2	10.8	16.4 ± 2.1	5.55 ± 1.3	23.5 ± 5.2	6.25 ± 0.6
3.	13	EG3	14.4	37.2 ± 2.3	13.9 ± 3.4	8.16 ± 2.0	9.57 ± 1.8
4.	14	EG4	18.0	14.9 ± 4.0	12.2 ± 2.1	13.6 ± 1.3	4.77 ± 1.5
5.	15	EG5	21.6	20.8 ± 5.5	12.8 ± 2.0	10.9 ± 2.3	3.20 ± 1.0
6.	16	EG7	28.8	30.7 ± 2.8	20.7 ± 1.6	32.3 ± 8.1	9.48 ± 1.4
7.	17	EG9	35.9	28.1 ± 3.7	7.92 ± 1.5	23.9 ± 6.9	7.85 ± 2.0
8.	18 b	EG10	39.5	17.2 ± 2.0 b	9.53 ± 2.4 b	-	-
9.	19	EG11	43.1	27.9 ± 4.0	7.17 ± 1.4	18.0 ± 5.0	7.60 ± 2.2
10.	19 b	EG11	43.1	21.8 ± 3.1 b	9.75 ± 0.57 b	-	-
11.	20	monovalent	19.2 c	78.1 ± 12	34.2 ± 1.7	12.4 ± 2.2	8.03 ± 0.01
12.	OHT	monovalent	-	285 d	62 e	5 d	-

^aExtended spacer length between two nitrogen atoms measured by using PyMOL.

^bThe ER-binding affinities for bivalent OHT ligands 18 and 19 were evaluated based on Z-Z:Z-E:E-E = 1:2:1 isomers according to analytical RP-HPLC analyses.

^cMaximum extended side chain length of EG₅Me.

^dReference 42.

^eReference 44.