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. Author manuscript; available in PMC: 2024 Jan 18.
Published in final edited form as: J Med Chem. 1996 Jan 19;39(2):398–406. doi: 10.1021/jm9504823

Table 1.

graphic file with name nihms-1956228-t0006.jpg
A. Affinities of Tetrahydrobenzothiophenone Derivatives in Radioligand-Binding Assays at A1 and A2a Adenosine Receptors
Ki (μM) or percent inhibitionc
compd R1 R2 X A1a A2ab A2a/A1
1 CO2CH2CH3 SCH3 =O 1.93 ± 0.21 3.66 ± 1.19 1.9
2 CO2CH2CH3 S(CH2)2CH3 =O 1.26 ± 0.30 4.69 ± 1.09 3.7
3 CO2CH2CH3 SCH(CH3)2 =O 1.79 ± 0.50 4.63 ± 0.15 2.6
4 CO2CH2CH3 SCH2CH=CH2 =O 1.06 ± 0.12 6.04 ± 0.44 5.7
5 CO2CH2CH3 S(CH2)3CH3 =O 1.42 ± 0.27 15.6 ± 2.3 11.0
6 CO2CH2CH3 SCH2CO2CH2CH3 =O 2.22 ± 0.39 25.6 ± 6.8 11.5
7 CO2CH2CH3 SCH2Ph =O 0.715 ± 0.116 1.36 ± 0.25 1.9
8 CO2CH2CH3 SCH3 OH, H 18.3 ± 1.9 33.5 ± 7.0 1.8
9 CO2CH2CH3 SCH3 =NOCH3 69.8 ± 9.4 22 ± 5% (10−4) >1.4
10 CONHNH2 SCH3 OH, H 71.2 ± 7.5 28.9% (10−4) >1.4
11 CONHNH2 SCH3 Hd 51.6 ± 6.8 c (10−4) >1.9
12 e H SCH3 =O 28 ± 7% (10−4) c (10−4) >1
13 e COOH SCH3 =O 69.4 ± 10.7 15 ± 5% (10−4) >1.4
14 COOH SCH2Ph =O 50.0 ± 2.3 15.2 ± 5.6 0.3
15 e CO2CH3 SCH2CH3 =O 3.34 ± 0.70 5.64 ± 0.85 1.7
16 e CO2CH2CH3 SCH2CH3 =O 2.69 ± 0.72 23.9 ± 2.6 8.9
17 e CO2CH2CH3 SCH(CH3)CH2CH3 =O 3.64 ± 0.84 106 ± 23 29.1
18 e CO2CH2CH3 SCH2Ph =O 0.567 ± 0.139 34 ± 2% (10−5) >17.6
19 e CO2CH2CH3 SO2CH3 =O 32.7 ± 2.3 13% (10−4) >3.1
20 e CO2CH2CH3 NHNH2 =O 17.5 ± 2.2 36.1 ± 5.1 2.1
B. Affinities of Selected Tetrahydrobenzothiophenone Derivatives in Radioligand-Binding Assays at Human and Rat A3 Adenosine Receptorsf
compd human A3 rat A3 human A3/rat A3 rat A3/rat A1
1 nd 15.2 ± 4.9 7.88
6 nd 10.2 ± 1.5 4.59
7 24%g nd
8 35.8 ± 0.5 15.4 ± 7.0 2.32 0.84
11 nd 13.1 ± 3.0 0.25
14 117 ± 13 42.0 ± 12.5 2.79 0.84
19 nd 51.8 ± 16.4 1.58
a

Displacement of specific [3H]PIA binding in rat brain membranes, expressed as Ki ± SEM in μM (n = 3–5).

b

Displacement of specific [3H]CGS21680 binding in rat striatal membranes, expressed as Ki ± SEM in μM (n = 3–6).

c

Displacement <10% of specific binding at concentration indicated.

d

C=C double bond at positions 4 and 5.

e

R3 = CH3.

f

Displacement of specific [125I]AB-MECA binding in CHO cell membranes transfected with rat A3 cDNA or HEK-293 cell membranes transfected with human A3 cDNA. Values are expressed as Ki ± SEM in μM (n = 3).

g

Percentage displacement of specific binding at 10−4 M.

h

Systematic name differs from numbering scheme for compounds 11 and 12. nd = not determined.