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. Author manuscript; available in PMC: 2012 Oct 24.
Published in final edited form as: J Med Chem. 1989 Aug;32(8):1873–1879. doi: 10.1021/jm00128a031

Table I.

Potencies of Xanthine Derivatives at Adenosine A1 and A2 Receptors in Nanomolar Concentration Unitsa,b

compd R R1 X graphic file with name nihms410759u1.jpg
Ki(A2)/Ki(A1)
Ki (A1 receptors) Ki (A2 receptors)
1a Me H O 8470 ± 1490c 25300 ± 2000a 2.99
1b Pr H O 450 ± 25c 5160 ± 590c 11.5
2a Me cyclopentyl O 10.9 ± 0.9c 1440 ± 70c 133
2b Pr cyclopentyl O 0.9 ± 0.1 410 ± 40 455
13 Me cyclopentyl S 10.2 ± 1.5 1390 ± 88 136
14 Pr cyclopentyl S 0.655 ± 0.058 314 ± 62 479
15a Me 2-furyl O 350 ± 20c 2780 ± 50c 7.94
15b Pr 2-furyl O 37 ±6 640 ± 100 16.8
15c Me 2-furyl S 182 ± 36 4450 ± 420 10.6
15d Pr 2-furyl S 32 ± 5 594 ± 71 18.6
16 Me 3-furyl O 72.4 ± 3.7c 984 ± 70c 13.6
17 Me 2-thienyl O 233 ± 48.6 1630 ± 179 6.97
18 Me 3-thienyl O 152 ± 27 841 ± 109 5.53
19 Pr 2-thienyl O 16.1 ± 1.96 381 ± 27.7 23.6
20 Pr 3-thienyl O 10.0 ± 0.03 121 ± 18.2 12.1
21 Me 2-thienyl S 221 ± 43.3 1740 ± 153 7.87
22 Pr 2-thienyl S 35.1 ± 6.0 >5000 >142
23 Me phenyl O 86.0 ± 2.8c 848 ± 115c 9.85
24 Et phenyl O 44.5 ± 1.2c 836 ± 73c 19.4
25 Pr phenyl O 10.2 ± 2.6c 180 ± 29c 17.8
26a Me phenyl S 38 ± 6 >7000 >184
26b Pr phenyl S 16.1 ± 2 422 ± 33 26.1
compd R2 graphic file with name nihms410759u2.jpg
Ki (A2)/Ki (A1)
X Ki (A1 receptors) Ki (A2 receptors)
27 COOH O 58 ± 3 2200 ± 526 37.8
28 COOH S 53.8 ± 7.1 315 ± 60.8 5.86
29 COOEt O 42 ± 3 >5000 >119
30 COOEt S 6.78 ± 0.64 >5000 >740
3 CONH(CH2)2NH2 O 1.2 ± 0.5 63 ± 21 52.5
31 CONH(CH2)2NH2 S 2.69 ± 0.77 26.3 ± 1.76 9.8
32 CONH(CH2)2NHCH3 O 15.1 ± 1.6d [9.3 ± 2.1]f [0.62]
33 CONH(CH2)2NHCH3 S 2.4 ± 0.28 6.80 ± 1.36 2.8
34 CONH(CH2)2N(CH3)2 O 2.8 ± 0.19d 5.03 ± 0.54 1.8
35 CONH(CH2)2N(CH3)2 S 2.55 ± 0.60 27.9 ± 7.5 11
36 CON(CH3)(CH2)2N(CH3)2 O 0.93 ± 0.03d 6.26 ± 0.25 6.7
37 CON(CH3)(CH2)2N(CH3)2 S 2.57 ± 0.67 24.5 ± 8.4 9.5
38 graphic file with name nihms410759t1.jpg O 12 e e
39 graphic file with name nihms410759t2.jpg S 84 870 10
40 graphic file with name nihms410759t3.jpg O 6.4 ± 2.7 191 ± 13 30
41 graphic file with name nihms410759t4.jpg S 8.9 322 ± 17 36
42 graphic file with name nihms410759t5.jpg O 0.87 ± 0.09 180 210
43 graphic file with name nihms410759t6.jpg S 13.0 ± 3.5 46.8 ± 9.4 3.6
44 graphic file with name nihms410759t7.jpg O 3.69 ± 0.71d 207 ± 57d 56
45 graphic file with name nihms410759t8.jpg S 33.5 e e
46 graphic file with name nihms410759t9.jpg O 18.3 ± 3.0 147 ± 5 8.1
47 graphic file with name nihms410759t10.jpg O 16.2 ± 2.7 458 ± 34 28.3
48 graphic file with name nihms410759t11.jpg O 11.3 ± 1.5 116 ± 25 10.3
49 graphic file with name nihms410759t12.jpg O 7.44 ± 0.98 630 ± 160 85
50 graphic file with name nihms410759t13.jpg O 17 ± 1.6 e e
51 graphic file with name nihms410759t14.jpg O 1.3 ± 0.12 e e
compd R R1 graphic file with name nihms410759u3.jpg
Ki (A2 receptors) Ki(A2)/Ki(A1)
X Ki (A1 receptors)
52 Me cyclopentyl S 40.5 ± 6.6 11500 ± 628 285
53 Pr cyclopentyl S 4.87 ± 0.82 2780 ± 730 572
54 Me cyclopentyl O 202 ± 26 8980 ± 1300 44.4
55 Pr cyclopentyl O 15.5 ± 1.5 3360 ± 270 217
56 Me phenyl O 1380 ± 74 11300 ± 777 8.18
57 Et phenyl O 1010 ± 321 3510 ± 290 3.47
a

Ki value from a single determination run in triplicate or average of three ± SEM.

b

Inhibition of binding of [3H](phenylisopropyl)-adenosine to A1 receptors in rat cortical membranes and binding of [3H]-5′-(N-ethylcarbamoyl)adenosine to A2-adenosine receptors in rat striatal membranes was measured as described.18,19

c

Values taken from Bruns et al.18

d

Values taken from Jacobson et al.10

e

Not determined.

f

Kb for inhibition of 5′-(N-ethylcarbamoyl)adenosine-stimulated adenylate cyclase, in pheochromocytoma PC12 cell membranes.10b