. Author manuscript; available in PMC: 2010 Apr 9.

Published in final edited form as: J Med Chem. 2009 Apr 9;52(7):1885–1902. doi: 10.1021/jm801354e

Table 1.

Functional activity and selectivity of the lead compound 9 and its initial analogs 14–20, and 26 at human 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors in a calcium flux assays using stably transfected HEK-293 cells.

	5-HT_2A					5-HT_2B					5-HT_2C					Selectivity

compd^a	EC₅₀ ±SEM(nM)		E_max ±SEM^b		n^c	EC₅₀ ±SEM(nM)		E_max ±SEM^b		n^c	EC₅₀ ±SEM(nM)		E_max ±SEM^b		n^c	2A/2C	2B/2C
1	10	±1.7	100%		15	1.0	±0.10	100%		15	0.09	±0.01	100%		11	111	11
(±)-14a	1399	±169	74%	±8%	2	85	±10	93%	±0.7%	3	13	±4.6	96%	±3%	3	106	6.4

1	27	±7.2	100%		11	1.4	±0.30	100%		9	0.25	±0.05	100%		7	108	5.8
9	NA				3	> 5 µM		29%	±12%	3	2697	±451	109%	±12%	5	-	-
(+)-14a	1396	±271	79%	±15%	4	37	±10	111%	±3%	3	5.2	±0.84	108%	±7%	4	268	7.2
(−)-14a	NA				4	3092	±1156	72%	±4%	3	909	±204	102%	±7%	4	> 10	3.4
(±)-14b	NA				5	> 10 µM		20%	±6%	4	3019	±1086	104%	±9%	7	-	-
15	NA				5	NA		6%	±9%	4	NA				6	-	-
16	NA				5	> 10 µM		26%	±7%	4	634	±205	101%	±6%	3	-	-
17	NA				4	NA		-2%	±2%	3	NA				7	-	-
18	NA				4	NA		-1%	±1%	3	3416	±1180	18%	±4%	6	-	-
19	NA				4	NA		-1%	±1%	3	NA				7	-	-
20	NA				5	NA		10%	±3%	4	5697	±2352	97%	±7%	6	-	-
26	NA				4	510	±292	21%	±5%	3	2902	±1314	60%	±7%	4	-	0.18

Tested in independent screening campaigns using different cell lines / passages

Percent of maximal activation by 5-HT; activation at 10 µM for compounds without EC₅₀ value

n: Number of concentration curves from ≥ 2 (typically ≥ 3)independent experiments NA: E_max ≤ 12%