Table 1. In Vitro Binding Affinities of 21 Quinuclidine anti-1,2,3-Triazole Derivatives Towards nAChRs^a.

		inhibition constant Ki in nM; mean ± SD			selectivityb (inverse of respective Ki ratio)
R	compd	α7c	α3β4d	α4β2d	α7 vs α3β4	α7 vs α4β2	α3β4 vs α4β2
p-F	(RS)-T1	72.8 ± 13	8.50 ± 0.50	449 ± 127	1/8.6	6.2	53
	(R)-T1	73.0 ± 15	1010 ± 162	10436 ± 1943	14	143	10
	(S)-T1	174.5 ± 66	3.09 ± 0.10	515 ± 64	1/56	3.0	167
m-F	(RS)-T2	133 ± 40	5.24 ± 0.35	748 ± 114	1/25	5.6	143
	(R)-T2	117 ± 4	362 ± 27	5201 ± 412	3.1	44	14
	(S)-T2	660.5 ± 139	2.25 ± 0.42	519 ± 20	1/294	1/1.3	231
m-O(CH2)2F	(RS)-T3	98.7 ± 39	20.9 ± 0.7	1962 ± 228	1/4.7	20	94
	(R)-T3	38.8 ± 8	558 ± 34	7050 ± 200	14	182	13
	(S)-T3	74.9 ± 20	11.8 ± 0.3	1262 ± 187	1/6.3	17	107
m-O(CH2)3F	(RS)-T4	74.6 ± 14	44.4 ± 8.0	3894 ± 252	1/1.7	52	88
	(R)-T4	62.3 ± 10	1628 ± 11	9010 ± 5,034	26	145	5.5
	(S)-T4	96.9 ± 17	19.5 ± 0.4	1980 ± 117	1/5.0	20	102
m-OBn	(RS)-T5	91.3 ± 9	7.57 ± 2.9	668 ± 7	1/12	7.3	88
	(R)-T5	22.5 ± 9	631 ± 206	5059 ± 374	28	225	8.0
	(S)-T5	279 ± 31	6.67 ± 0.7	414 ± 59	1/42	1.5	62
m-OCH2C6H4F	(RS)-T6	127 ± 5	13.9 ± 2.8	1,013 ± 107	1/9.1	8.0	73
	(R)-T6	33.2 ± 7	1090 ± 163	6392 ± 230	33	193	5.9
	(S)-T6	149 ± 42	7.17 ± 1.2	537 ± 11	1/21	3.6	75
p-OH	(RS)-QND8	9.61 ± 1.47	3.44 ± 0.04	627 ± 52	1/2.8	65	182
	(R)-QND8	10.9 ± 1.42	138 ± 0	7389 ± 42	12.7	678	54
	(S)-QND8	29.3 ± 0.18	2.48 ± 0.04	461 ± 89	1/11.8	16	186

^aBinding affinities are represented by the inhibition constant K_i determined for individual compounds in two separate experiments each performed as triplicate.

^bSelectivity is reported in terms of the reciprocal of the ratio of the respective K_i values.

^cHuman α7 nAChR in stably transfected SH-SY5Y cells, with radiotracer [³H]methyllycaconitine (0.5–1 nM); K_d = 2.0 nM.

^dHuman α4β2 and α3β4 nAChR in stably transfected HEK-293 cells, with radiotracer [³H]epibatidine (0.5–1 nM); K_d = 0.025 nM for hα4β2 nAChR; K_d = 0.117 nM for hα3β4 nAChR.