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. Author manuscript; available in PMC: 2016 Feb 2.
Published in final edited form as: Medchemcomm. 2015 Feb 2;6:555–563. doi: 10.1039/C4MD00571F

Table 2.

Structures and binding affinitiesa of AR agonists, including reference compounds 1-4, triazole derivatives 5-20 and their synthetic intermediates 25-34.

graphic file with name nihms662588u1.jpg
Compd. R1 R2 or R3 A1AR% inhibition or Ki (nM)a A2AAR% inhibitionc A3AR% inhibition or Ki (nM)a
1b,d graphic file with name nihms662588t1.jpg graphic file with name nihms662588t2.jpg 6 ± 4% 41 ± 10% 3.49±1.84,3.08±0.23 (m)
2b,d CH3 graphic file with name nihms662588t3.jpg 6 ± 1%, 24 ± 13%, 0.70 ± 0.11,36.1±4.7 (m)
4b,d CH3 graphic file with name nihms662588t4.jpg 25 ± 2% 47 ± 2% 2.68 ± 0.44
5d CH3 graphic file with name nihms662588t5.jpg 18 ± 4% 35 ± 8% 0.96 ± 0.07
6 CH3 graphic file with name nihms662588t6.jpg 20 ± 5% 31 ± 6% 0.95 ± 0.50
7 CH3 graphic file with name nihms662588t7.jpg 9 ± 4% 39 ± 4% 1.06 ± 0.10
8 CH3 graphic file with name nihms662588t8.jpg 29 ± 7% 26 ± 2% 1.84 ± 0.38
9 CH3 graphic file with name nihms662588t9.jpg 14 ± 7% 27 ± 3% 3.48 ± 0.97,334 ± 49 (m)
10 CH3 graphic file with name nihms662588t10.jpg 25 ± 10% 8 ± 3% 2.21 ± 0.34
11 CH3 graphic file with name nihms662588t11.jpg 2 ± 2% 1 ± 1% 2.16 ± 0.32
12 CH3 graphic file with name nihms662588t12.jpg 43 ± 2% 51 ± 1% 0.96 ± 0.09
13 CH3 graphic file with name nihms662588t13.jpg 12 ± 7% 40 ± 6% 1.25 ± 0.27
14 CH3 graphic file with name nihms662588t14.jpg 27 ± 8% 34 ± 5% 0.73 ± 0.10
15d C2H5 graphic file with name nihms662588t15.jpg 15 ± 11% 32 ± 5% 1.22 ± 0.26,9.64 ± 0.84 (m)
16 graphic file with name nihms662588t16.jpg graphic file with name nihms662588t17.jpg 77% ND 7.05 ± 5.81,14.2 ± 0.2 (m)
17 graphic file with name nihms662588t18.jpg graphic file with name nihms662588t19.jpg 65% ND 9.02 ± 5.78,6.53 ± 0.58 (m)
18 graphic file with name nihms662588t20.jpg graphic file with name nihms662588t21.jpg 58% ND 6.66 ± 2.07
19 CH3 graphic file with name nihms662588t22.jpg 33 ± 7% 7 ± 6% 0.58 ± 0.17
20 CH3 graphic file with name nihms662588t23.jpg 23 ± 3% 54 ± 2% 3.09 ± 0.21
25b CH3 I ND ND 1.91 ± 0.85
26 CH2CH3 I 1910 ± 300 11 ± 7% 1.22 ± 0.21
27 graphic file with name nihms662588t24.jpg I 93% >10,000 1.53 ± 0.45
28b graphic file with name nihms662588t25.jpg I 2200e >10,000 3.6
29 graphic file with name nihms662588t26.jpg I 68% 42% 0.91 ± 0.14
30 CH3 N3 77 ± 1% 1 ± 1% 0.54 ± 0.10
31 CH2CH3 N3 707 ± 152 11 ± 6% 0.69 ± 0.08
32 graphic file with name nihms662588t27.jpg N3 100% 46% 0.85 ± 0.10
33 graphic file with name nihms662588t28.jpg N3 ND 2770e 1.08 ± 0.75
34 graphic file with name nihms662588t29.jpg N3 93% 1110e 0.85 ± 0.10
a

Binding in membranes prepared from CHO or HEK293 (A2A only) cells stably expressing one of three hAR subtypes, unless noted. The binding affinity for hA1, A2A and A3ARs was expressed as Ki values (n = 3–4, unless noted), measured using agonist radioligands [3H]N6-R-phenylisopropyladenosine 35, [3H]2-[p-(2-carboxyethyl)phenyl-ethylamino]-5′-N-ethylcarboxamido-adenosine 36, or [125I]N6-(4-amino-3-iodobenzyl)adenosine-5′-N-methyl-uronamide 37, respectively. Additional values designated (m) are for mouse ARs. A percent in italics refers to inhibition of binding at 10 μM. Nonspecific binding was determined using 38 (10 μM). Values are expressed as the mean ± SEM. Ki values were calculated as reported.24

b

Data from Tosh et al.7,8 and Melman et al.25

c

Percent of inhibition at 10 μM.

d

1, MRS5698; 2, MRS5980; 4, MRS5979; 5, MRS7110; 15, MRS7126; 17, MRS7138.

e

n = 1.

ND – not determined.