Table 1.

In vitro activity of synthesized compounds on hTRPV1^a

	A	B	C	Binding affinity Ki(nM)		Agonism EC50 (nM)	Antagonism Ki(ant) (nM)
1	–NH	CH–Me	CH2	7.90	(±1.6)	NE	2.22	(±0.47)
1S	–NH	(S)-CH–Me	CH2	2.95	(±0.73)	NE	1.26	(±0.28)
11	–NH	CH–Me	(CH2)2	54	(±13)	NE	95	(±26)
16	–CH2NH	CH–Me	CH2	230	(±32)	NE	27.6	(±5.5)
21	–NH	NH	CH2	83	(±27)	NE	149	(±50)
22	–NH	NH	(CH2)2	210	(±46)	29%	49%
27	–CH2NH	NH	CH2	6.77	(±0.48)	NE	12.5	(±4.2)
31	–NH	NHCH2–	CH2	59	(±12)	NE	18.7	(±6.1)
32	–NH	NHCH(Me)–	CH2	31.6	(±3.4)	NE	28.1	(±8.5)
34	–CH2NH	NHCH2–	CH2	410	(±27)	NE	199	(±50)
41	–NH	NH–Me	CH2	1160	(±180)	NE	59	(±20)
42	–NH	NH–Ph(3-Me)	CH2	490	(±120)	NE	860b	(±290)b

^aNE: no effect; values are the mean ± SEM of at least three experiments; where indicated, % represents the % agonism or antagonism at 3–30 μM.

^bMeasured with 30 min pre-incubation before challenge with capsaicin; value with 15 min pre-incubation K_i(ant) = 2200 ± 560 nM.