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. Author manuscript; available in PMC: 2009 Oct 15.
Published in final edited form as: Bioorg Med Chem. 2008 Aug 26;16(20):9349–9358. doi: 10.1016/j.bmc.2008.08.048

Table 1.

Activities of the 1,4-dihydropyridine derivatives as enhancers at the TRPV1 receptor ectopically expressed in NIH3T3 cells.

graphic file with name nihms74718t1.jpg
No R2 R3 R4 R6 EC50(µM) ±
SEM		 Hill Slope ±
SEM		 Emax(%)a ±
SEM		 nb
3-Esters
7d CH3 CH3CH2O CH3CH2 Ph — c — 383 ± 39 3
8d CH3 CH3CH2O (CH3O) 2CH Ph — — 114 ± 24 2
9 CH3 CH3CH2O CH3CH2 3-Cl-Ph 17.1 ± 1.2 1.45 ± 0.28 347 ± 24 3
10 CH3 CH3CH2O CH3CH2 3-F-Ph 26.7 ± 1.1 1.98 ± 0.30 403 ± 21 3
11 CH3 CH3CH2O CH3CH2 4-F-Ph 29.2 ± 1.2 1.86 ± 0.42 372 ± 33 3
3-Thioesters
12d CH3 CH3CH2S CH3CH2 Ph 28.1 ± 1.0 1.55 ± 0.17 435 ± 11 3
13 CH3 CH3CH2S CH3CH2 2-F-Ph — — 198 ± 2 2
14e CH3 CH3CH2S CH3CH2 3-F-Ph 21.8 ± 1.2 1.59 ± 0.33 446 ± 39 3
15 CH3 CH3CH2S CH3CH2 4-F-Ph 28.4 ± 1.2 1.82 ± 0.33 409 ± 32 3
16 CH3 CH3CH2S CH3CH2 4-CN-Ph — — 129 ± 2 2
17 CH3 CH3CH2S CH3CH2 cyclohexyl — — 87 ± 8 2
18d CH3 CH3CH2S CH3CH2CH2 Ph 22.4 ± 1.2 1.38 ± 0.23 364 ± 16 3
19 CH3 CH3CH2S CH3CH2CH2 3-Cl-Ph — — 177 ± 19 2
20 CH3 CH3CH2S cPr 4-F-Ph — — 175 ± 4 2
21d CH3CH2 CH3CH2S CH3CH2 Ph — — 257 ± 17 3
22d CH3CH2CH2 CH3CH2S CH3CH2 Ph — — 148 ± 3 2
23d,e CH3 CH3OCH2CH2S CH3CH2 Ph 21.3 ± 1.1 1.79 ± 0.17 626 ± 25 3
24 CH3 (CH3)2CHS CH3CH2 2-F-Ph — — 124 ± 4 2
25 CH3 PhCH2S CH3CH2 2-F-Ph — — 123 ± 1 2
26 CH3 PhCH2CH2S CH3CH2CH2 Ph 27.6 ± 1.5 1.14 ± 0.32 360 ± 35 3
27 CH3 PhCH2CH2S CH3CH2 2-F-Ph — — 117 ± 4 2
28 CH3 PhCH2CH2S CH3CH2 3-Cl-Ph — — 194 ± 29 2
29 CH3 PhCH2CH2S CH3CH2 4-F-Ph 51.6 ± 1.6 1.18 ± 0.25 232 ± 7 3
30 CH3 PhCH2CH2S CH3CH2 4-NO2-Ph — — 101 ± 3 2
31 CH3 PhCH2S CH3CH2 4-NO2-Ph — — 98 ± 3 2
32 CH3 CH3CH2S CH3CH2 2-naphthyl — — 116 ± 19 2
a

Emax = TRPV1 activation at [Enhancer]max (100 µM), expressed as % of control (2 µM capsaicin).

b

“n” represents the number of separate assay plate runs, with compounds in duplicate wells per assay.

c

For compounds where EC50 and Hill Slope could not be calculated (i.e., the data could not be curve fitted), only the Emax is shown.

d

Ki value in binding to the human A3 adenosine receptor, in µM (corresponding compound number in ref. 27): 7, 2.27 (9); 8, 15.3 (14); 12, 2.01 (10); 18, 2.17 (12); 21, 0.907 (21); 22, 2.09 (22); 23, 4.58 (11).

e

Compound 23 is MRS1477; 14 is MRS3625.