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. Author manuscript; available in PMC: 2013 Jan 12.
Published in final edited form as: J Med Chem. 2011 Dec 12;55(1):538–552. doi: 10.1021/jm201461q

Table 3.

Binding affinity of a series of adenosine C2 long chain amide derivatives of 16 at three subtypes of human ARs.

graphic file with name nihms341208t25.jpg
Compd R = Affinity
Ki, nM or (% inhibition)a 		Efficacy (A2A),
% of maximalb
A1 A2A A3
16 OH 380 70 570 100
27 L-Phe-OMe 1080 ± 210 160 ± 50 130 ± 40 110.9 ± 2.5
28 D-Phe-OMe 1230 ± 180 84.3 ± 3.0 160 ± 80 92.6 ± 12.4
29 L-Trp-OMe 1670 ± 260 87.2 ± 3.8 140 ± 10 104.5 ± 13.6
30 D-Trp-OMe 1610 ± 100 130 ± 4 250 ± 90 118.6 ± 5.7
33 L-Asp-OH 1900 ± 660 180 ± 60 1460 ± 600 94.8 ± 6.7
34 D-Asp-OH 1180 ± 360 110 ± 10 790 ± 160 94.3 ± 7.3
35 L-Arg-OH 1110 ± 30 100 ± 4 620 ± 250 94.5 ± 5.8
36 D-Arg-OH 990 ± 320 50 ± 5 220 ± 60 94.7 ± 6.7
37 L-Phe-OH 640 ± 170 63.7 ± 13.1 260 ± 140 103.3 ± 13.8
38 D-Phe-OH 550 ± 100 34.0 ± 3.2 140 ± 30 93.4 ± 12.4
39 L-Trp-OH 1060 ± 310 71.7 ± 16.9 200 ± 50 95.8 ± 7.4
40 D-Trp-OH 2160 ± 280 130 ± 30 520 ± 60 113.3 ± 5.0
41 L-His-OH 1000 ± 160 110 ± 30 830 ± 290 105.2 ± 4.9
42 D-His-OH 350 ± 40 40 ± 4 320 ± 150 105.9 ± 6.5
a

Using CHO or HEK293 (A2A only) cells stably expressing a human AR (Supporting Information); affinity was expressed as Ki value (n = 3–5) or percent inhibition of radioligand binding at 10 µM. Compounds 31 and 32 are conjugates of L- and D-His-OMe, respectively, and were not tested biologically.

b

Maximal efficacy (at 10 µM) in an A2AAR functional assay, determined by stimulation of cyclic AMP production in stably transfected CHO cells, expressed as percent (mean ± standard error, n = 3 – 5) in comparison to effect (100%) of full agonist 16 at 10 µM.