. 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 2.

Functional activity of compounds 27–61 in calcium flux assays using HEK-293 cells stably expressing the human 5-HT_2A, 5-HT_2B, or 5-HT_2C receptor.


					5-HT_2A					5-HT_2B					5-HT_2C					Selectivity

compd^a	R²	R³	R⁴	R⁶	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					17	±7.1	100%		14	3.0	±1.5	100%		12	0.12	±0.08	100%		17	134	24
27	F				> 1000		52%	±10%	3	1549	±821	65%	±16%	4	37	±19	94%	±5%	4	> 27	42
28	Cl				403	±53	54%	±33%	3	84	±13	82%	±4%	3	5.1	±4.2	98%	±14%	3	79	16
29	Br				585	±178	73%	±13%	3	154	±131	86%	±19%	4	2.8	±2.2	93%	±8%	3	206	54
31	CF₃				NA				2	350	±7.1	102%	±27%	2	49	±11	101%	±8%	2	-	7.2
34		F			1769	±2110	71%	±7%	2	51	±16	106%	±9%	3	3.9	±3.9	92%	±6%	3	450	13
35		Cl			1886	±540	42%	±9%	2	59	±3.8	78%	±7%	2	10.0	±0.20	98%	±4%	2	189	5.9
36		Br			1680	±1368	55%	±13%	4	141	±143	74%	±14%	5	14	±11	90%	±10%	5	123	10
38		CF₃			1485	±195	35%	±1%	2	77	±16	78%	±16%	2	30	±8.8	94%	±4%	2	50	2.6
41			F		1098	±971	67%	±5%	4	312	±150	95%	±6%	3	5.4	±2.1	93%	±4%	2	202	57
42			Cl		4482	±2026	64%	±15%	2	404	±28	80%	±11%	2	76	±22	106%	±21%	2	59	5.3
43			Br		> 1000		26%	±5%	2	2737	±1540	51%	±16%	3	138	±82	87%	±4%	5	> 7	20
45			CF₃		NA				3	> 1000		56%	±10%	3	779	±286	91%	±4%	3	-	> 1
46			OMe		NA				2	NA				2	902	±442	86%	±6%	2	-	-
47			OH		NA				2	NA				2	NA				2	-	-
50	F			F	> 1000		38%	±22%	4	3342	±2622	58%	±9%	5	87	±76	85%	±14%	5	> 11	39

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
27	F				942	±30	79%	±8%	2	199	±34	89%	±3%	3	29	±6.4	91%	±0.6%	3	32	6.8
28	Cl				168	±21	87%	±8%	2	32	±3.8	95%	±3%	3	5.5	±2.0	94%	±4%	3	31	5.8
30	Me				1606	±940	69%	±4%	2	53	±19	86%	±2%	2	23	±8.3	99%	±6%	2	71	2.3
32	OMe				2166	±773	61%	±7%	4	199	±26	83%	±6%	4	26	±7.0	93%	±2%	4	84	7.7
33	OH				513	±177	81%	±8%	3	492	±28	74%	±8%	3	161	±62	94%	±5%	3	3.2	3.1
34		F			733	±59	86%	±3%	2	13	±2.5	96%	±3%	3	3.3	±1.0	97%	±3%	3	225	4.0
37		Me			585	±148	86%	±4%	4	65	±15	93%	±2%	5	4.8	±1.3	95%	±2%	4	123	14
39		OMe			613	±157	90%	±3%	4	75	±13	96%	±4%	4	16	±5.9	97%	±2%	4	39	4.8
40		OH			247	±138	92%	±3%	3	5.5	±1.3	98%	±1%	3	3.3	±1.6	94%	±0.7%	3	75	1.7
41			F		646	±34	80%	±2%	2	57	±4.8	94%	±2%	3	8.4	±2.5	94%	±1%	3	77	6.8
48	F	F			> 5 µM		45%	±9%	2	366	±88	93%	±2%	2	99	±37	101%	±6%	2	> 50	3.7
49	F		F		547	±296	85%	±2%	2	415	±151	88%	±1%	2	42	±18	98%	±0.5%	2	13	9.9
51		F	F		578	±219	96%	±4%	2	28	±7.2	96%	±0.1%	2	9.0	±3.3	103%	±6%	2	64	3.2
52	F		Cl		774	±229	83%	±6%	3	459	±154	86%	±2%	3	128	±66	94%	±4%	3	6.1	3.6
53	Cl		F		91	±33	91%	±6%	4	22	±8.6	97%	±4%	4	3.0	±1.2	100%	±2%	4	30	7.3
54	Cl	Cl			349	±54	77%	±2%	4	14	±1.9	89%	±2%	5	11	±4.1	96%	±3%	4	33	1.4
55	Cl		Cl		51	±18	88%	±3%	4	83	±21	89%	±6%	4	18	±10	98%	±1%	4	2.9	4.7

1					27	±7.2	100%		11	1.4	±0.30	99%		9	0.25	±0.05	100%		7	108	5.8
59	Me	Me			360	±65	59%	±7%	4	8.4	±0.81	90%	±4%	3	7.0	±1.2	107%	±8%	5	52	1.2
60		Me	Me		2392	±692	40%	±6%	4	12	±2.4	78%	±5%	3	35	±8.4	97%	±7%	4	68	0.33
61	F	Me		Cl	330	±116	65%	±9%	3	116	±51	74%	±11%	3	13	±2.7	117%	±11%	4	26	9.2
(+)-29	Br				67	±12	76%	±17%	4	13	±4.8	102%	±4%	3	0.78	±0.18	116%	±5%	4	86	17
(−)-29	Br				NA				4	224	±103	96%	±4%	3	78	±11	113%	±4%	4	> 128	2.9
7	5-HT_2C agonist				616	±270	26%	±8%	3	219	±107	92%	±0.7%	3	2.7	±0.90	124%	±13%	4	232	82

1					5.8	±0.63	100%		11	0.50	±0.04	100%		8	0.16	±0.02	100%		9	37	3.2
27	F				681	±116	62%	±3%	5	69	±7.8	84%	±4%	4	33	±2.3	91%	±2%	5	20	2.1
29	Br				94	±9.5	71%	±2%	5	4.8	±1.7	87%	±6%	4	1.3	±0.54	76%	±19%	5	73	3.7
34		F			437	±28	73%	±4%	5	3.6	±0.41	87%	±5%	4	3.3	±0.49	96%	±2%	5	131	1.1
41			F		508	±35	68%	±3%	5	21	±0.90	89%	±4%	4	11	±1.2	96%	±2%	5	47	1.9
44			Me		1929	±300	18%	±3%	4	37	±3.2	79%	±4%	4	135	±51	69%	±17%	5	14	0.28
56		Me	F		235	±47	73%	±5%	4	4.9	±0.35	83%	±5%	4	6.0	±1.4	91%	±4%	4	39	0.83
57	Cl			Me	726	±62	56%	±6%	5	7.0	±0.49	90%	±4%	4	3.5	±1.0	97%	±3%	4	207	2.0
58	Br		Me		465	±95	62%	±6%	5	116	±10	68%	±4%	4	97	±20	84%	±5%	4	4.8	1.2
6	5-HT_2C agonist				NA				6	NA				4	261	±41	69%	±3%	5	-	-
7	5-HT_2C agonist				151	±16	33%	±3%	11	39	±3	92%	±1.7%	8	3.0	±0.54	96%	±2%	9	51	13

Tested in four 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: Emax ≤ 12%