Table 1. 5-HT₃R Binding Affinities of Bivalent Ligands 3–5 and Reference Monovalent Ligands 6.

compd	probea	spacer (met. equiv.)b	Ki (nM)c	RPd
3a	MPQC	–(CH2)6– (6)	28 ± 7.1	10
3b	MPQC	–(CH2)7– (7)	2.7 ± 0.7	1
3c	MPQC	–(CH2)8– (8)	67 ± 15	25
3d	MPQC	–CH2–CH2–O–CH2–CH2–O–CH2–CH2– (8)	7.7 ± 1.5	3
3e	MPQC	–CH2–CH2–O–(CH2–CH2–O)6–CH2–CH2– (23)	27 ± 8.2	10
3f	MPQC	–CH2–CH2–O–(CH2–CH2–O)8–CH2–CH2– (29)	15 ± 2.4	5
4a	tacrine	–(CH2)6– (6)	71 ± 22	13
4be	tacrine	–(CH2)7– (7)	5.6f	1
4c	tacrine	–(CH2)8– (8)	69 ± 17	12
5be	UAA	–(CH2)7– (7)	26g	1
5de	UAA	–CH2–CH2–O–CH2–CH2–O–CH2–CH2– (8)	141g	5
5e	UAA	–CH2–CH2–O–(CH2–CH2–O)6–CH2–CH2– (23)	106 ± 18	4
5f	UAA	–CH2–CH2–O–(CH2–CH2–O)8–CH2–CH2– (29)	154 ± 21	6
6a	NH-Boc	–(CH2)6– (6)	178 ± 32	10
6b	NH-Boc	–(CH2)7– (7)	18 ± 3.1	1
6c	NH-Boc	–(CH2)8– (8)	127 ± 23	7
6d	NH-Boc	–CH2–CH2–O–CH2–CH2–O–CH2–CH2– (8)	132 ± 25	7
6e	NH-Boc	–CH2–CH2–O–(CH2–CH2–O)6–CH2–CH2– (23)	89 ± 18	5
6f	NH-Boc	–CH2–CH2–O–(CH2–CH2–O)8–CH2–CH2– (29)	71 ± 17	4

^aSee Figure 1.

^bMethylene equivalents.

^cEach value is the mean ± SEM of three determinations and represents the concentration producing half the maximum inhibition of [³H]granisetron (final concentration, 1 nM) specific binding to rat cortical membranes.

^dRelative potency with respect to the compound bearing the heptamethylene spacer (expressed as the ratio between the K_i value of the compound and that of the analogue showing the same probe and the heptamethylene spacer).

^eCompounds 4b and 5b,d are cited in the introduction as 1 and 2a,b, respectively.

^fSee ref (5).

^gSee ref (6).