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. Author manuscript; available in PMC: 2024 Dec 31.
Published in final edited form as: J Med Chem. 1998 Jul 16;41(15):2835–2845. doi: 10.1021/jm980094b

Table 1.

Affinities or Antagonistic Activities of Triazoloquinazoline Derivatives in Radioligand Binding Assays at A1, A2A, and A3 Receptorsa–c

graphic file with name nihms-2044185-t0001.jpg
compd R Ki or IC50 (nM)
rA1 rA2A hA3 rA1/hA3 rA2A/hA3
1a (CGS 15943) H 21 ± 3.0d 3.3 ± 1.7d 13.8 ± 2.4
1b COCH2-Ph 52.7 ± 11.8e 10.3 ± 3.7e 0.65 ± 0.25 81 16
3 CH2-Ph 1200 ± 15 200 ± 34 42.5 ± 6.91 28 4.7
4 COCH2-(4-CH3O-Ph) 30.2 ± 6.3 28.0 ± 4.8 14.4 ± 3.2 2.1 1.9
5 COCH2-(4-NH2-3-I-Ph) 217 ± 65 10.4 ± 2.2 49.3 ± 17.9 4.4 0.21
6 COCH2-(4-NH2-Ph) 24.9 ± 7.7 6.97 ± 1.13 3.56 ± 1.24 7.0 2.0
7 COCH2-(2-I-Ph) 2300 ± 590 17.2 ± 4.0 >10000 <1 ≪1
8 COCH2-(3-I-Ph) 45.4 ± 8.7 9.67 ± 1.74 882 ± 242 0.051 0.011
9 COCH2-(4-I-Ph) 13.8 ± 4.6 9.93 ± 2.00 62.9 ± 13.0 0.22 0.16
10 COCH2-(3-Cl-Ph) 43.0 ± 6.4 9.43 ± 2.65 32.1 ± 11.3 1.3 0.29
11 (R)-COCH(CH3)(Ph) 46.2 ± 11.9 11.1 ± 1.3 0.362 ± 0.053 130 31
12 (S)-COCH(CH3)(Ph) 37.5 ± 8.5 20.1 ± 3.7 0.468 ± 0.111 80 43
13 COCH(Ph)2 129 ± 43 12.1 ± 3.4 0.586 ± 0.196 220 21
14 COC(CH3)(Ph)2 890 ± 131 453 ± 156 194 ± 42 4.6 2.3
15 COCH2CH2-Ph 45.2 ± 7.5 28.3 ± 10.3 23.6 ± 7.6 1.9 1.6
16 COCH=CH-Ph (trans) 282 ± 71 59.8 ± 13.4 72.1 ± 15.6 3.9 0.71
17 d-COCH(CH3)(NH-Boc) 48.6 ± 6.7 18.8 ± 5.3 46.3 ± 5.4 1.0 0.41
18 L-COCH(CH3)(NH-Boc) 54.7 ± 13.4 6.65 ± 1.56 82.9 ± 2.7 0.66 0.080
19 CO(CH2)2-NH-Boc 31.0 ± 2.2 7.58 ± 0.80 6.71 ± 0.67 4.6 1.1
20 CO(CH2)3-NH-Boc 45.9 ± 13.2 19.9 ± 4.6 32.9 1.4 0.60
21 CO(CH2)4-NH-Boc 30.1 ± 6.8 3.64 ± 0.34 22.0 ± 3.1 1.4 0.17
22 CO(CH2)5-NH-Boc 53.8 ± 12.7 33.7 ± 7.3 33.8 ± 10.2 1.6 1.0
23 CO(CH2)6-NH-Boc 38.2 ± 2.6 11.1 ± 1.9 53.7 ± 31.0 0.71 0.21
24 d-COCH(CH3)(NH2) 193 ± 17 29.7 ± 9.1 1140 ± 370 0.17 0.026
25 l-COCH(CH3)(NH2) 390 ± 127 143 ± 13 1200 ± 460 0.33 0.12
26 CO(CH2)2-NH2 89.8 ± 23.3 7.58 ± 2.1 874 ± 4 0.10 0.0088
27 CO(CH2)3-NH2 8.75 ± 2.28 1.38 ± 0.23 80.8 ± 7.4 0.11 0.017
28 CO(CH2)4-NH2 6.99 ± 1.38 1.13 ± 0.41 57.9 ± 20.8 0.12 0.020
29 CO(CH2)5-NH2 99.6 ± 6.7 10.3 ± 3.7 213 ± 27 0.47 0.048
30 CO(CH2)6-NH2 114 ± 26 55.9 ± 5.5 346 ± 77 0.33 0.16
31 CO(CH2)4-COOBn 304 ± 126 16.7 ± 2.5 44.7 ± 14.1 6.8 0.37
32 CO(CH2)2-COOCH3 71.8 ± 7.2 28.8 ± 10.7 55.1 ± 8.6 1.3 0.52
33 CO(CH2)6-COOCH3 46.6 ± 10.5 7.43 ± 2.72 59.0 ± 18.1 0.79 0.13
34 CO(CH2)3-COOH 45 ± 4 1.15 ± 0.47 81.3 ± 11.0 0.55 0.014
a

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

b

Displacement of specific [3H]CGS 21680 binding in rat striatal membranes, expressed as Ki ± SEM (n = 3–6).

c

Displacement of specific [125I]AB-MECA binding at human A3 receptors expressed in HEK cells, in membranes, expressed as Ki ± SEM (n = 3–4).

d

IC50 values for 1a (see ref 20).

e

Previously reported Ki values were 305 and 52.0 nM for rat A1 and A2A receptors, respectively.20