Pharmacophore ModelingofHuman Adenosine Receptor A2A Antagonists
Zhejun Xu, Feixiong Cheng, Chenxiao Da, Guixia Liu, Yun Tang*
School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China
*Corresponding author. Tel: +86-21-64251052; Fax:+86-21-64253651
E-mail address:
Supplementary Materials
Table S1. Molecular Structures,Experimental Binding Affinity and Predicted Values of A2A Antagonists for Test Set.
Table S2. Molecular Structures,Experimental Binding Affinity and Hits forSimulated VirtualScreeningDatabase.
Supplementary Materials
Table S1. Molecular Structures,Experimental Binding Affinity and Predicted Values of A2A Antagonists for Test Set.
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref1 / / 0.12 / 0.54 / [1]
2 / / 0.19 / 0.79 / [1]
3 / / 0.43 / 0.44 / [2]
4 / / 0.6 / 5.1 / [3]
5 / / 0.8 / 7.7 / [2]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref6 / / 1 / 7.3 / [2]
7 / / 1.31 / 7.7 / [2]
8 / / 2.1 / 15 / [1]
9 / / 3.3 / 20 / [4]
10 / / 3.8 / 7.7 / [2]
11 / / 4 / 0.51 / [2]
12 / / 4.1 / 23 / [1]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref13 / / 4.4 / 0.69 / [5]
14 / / 4.7 / 19 / [4]
15 / / 5.48 / 0.56 / [2]
16 / / 6.6 / 21 / [4]
17 / / 10 / 25 / [6]
18 / / 20 / 160 / [6]
19 / / 20 / 130 / [6]
20 / / 20 / 81 / [6]
21 / / 20 / 27 / [6]
22 / / 20.2 / 23 / [5]
Table S1 continued…
Compound No / 2D structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref23 / / 21 / 230 / [1]
24 / / 23 / 170 / [7]
25 / / 31 / 210 / [7]
26 / / 39 / 270 / [8]
27 / / 40 / 28 / [6]
28 / / 46 / 270 / [9]
29 / / 46.3 / 330 / [4]
30 / / 50 / 8 / [2]
31 / / 51.6 / 270 / [4]
Table S1 continued…
Compound No / 2D structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref32 / / 60 / 160 / [6]
33 / / 61 / 23 / [10]
34 / / 65 / 190 / [5]
35 / / 70 / 65 / [6]
36 / / 70.4 / 330 / [4]
37 / / 80 / 64 / [5]
38 / / 83.7 / 240 / [4]
39 / / 87 / 260 / [9]
40 / / 87 / 260 / [7]
41 / / 89 / 150 / [7]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref42 / / 90 / 130 / [11]
43 / / 100 / 260 / [1]
44 / / 100 / 73 / [6]
45 / / 100 / 110 / [6]
46 / / 106 / 360 / [7]
47 / / 110 / 260 / [1]
48 / / 114 / 160 / [8]
49 / / 118 / 260 / [7]
50 / / 120 / 16 / [1]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref51 / / 120 / 280 / [1]
52 / / 120 / 270 / [4]
53 / / 140 / 150 / [1]
54 / / 140 / 280 / [1]
55 / / 143 / 190 / [1]
56 / / 151 / 250 / [7]
57 / / 156 / 160 / [1]
58 / / 160 / 120 / [1]
59 / / 180 / 84 / [1]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref60 / / 180 / 260 / [1]
61 / / 180 / 49 / [1]
62 / / 189 / 210 / [8]
63 / / 192 / 270 / [8]
64 / / 194 / 140 / [8]
65 / / 200 / 79 / [1]
66 / / 201 / 270 / [7]
67 / / 210 / 230 / [7]
68 / / 230 / 99 / [3]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref69 / / 230 / 180 / [8]
70 / / 248 / 250 / [1]
71 / / 287 / 190 / [7]
72 / / 287 / 190 / [7]
73 / / 335 / 63 / [1]
74 / / 350 / 390 / [12]
75 / / 360 / 200 / [9]
76 / / 360 / 360 / [12]
77 / / 370 / 43 / [9]
78 / / 370 / 160 / [12]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref79 / / 381 / 290 / [1]
80 / / 400 / 390 / [9]
81 / / 403 / 170 / [7]
82 / / 423 / 240 / [1]
83 / / 481.3 / 320 / [4]
84 / / 503 / 130 / [5]
85 / / 520 / 200 / [1]
86 / / 545 / 360 / [5]
87 / / 594 / 270 / [1]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref88 / / 600 / 370 / [9]
89 / / 680 / 280 / [1]
90 / / 695 / 280 / [1]
91 / / 700 / 810 / [6]
92 / / 700 / 140 / [6]
93 / / 760 / 220 / [12]
94 / / 780 / 280 / [9]
95 / / 880 / 300 / [9]
96 / / 940 / 110 / [9]
97 / / 1000 / 190 / [6]
Table S1 continued…
Compound No / 2D Structure / Experimental Values (Ki, nM ) / Predicted Values (Ki, nM ) / Ref98 / / 1040 / 230 / [1]
99 / / 1100 / 160 / [9]
100 / / 1200 / 220 / [6]
101 / / 1390 / 190 / [1]
102 / / 1900 / 210 / [12]
103 / / 2000 / 370 / [9]
104 / / 2600 / 270 / [9]
105 / / 3800 / 390 / [12]
106 / / 8100 / 3200 / [3]
Table S2. Molecular Structures,Experimental Binding Affinity and Hits forSimulated VirtualScreeningDatabase.
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A2A-anta-01 / / 0.6 / yes / [3]
A2A-anta-02 / / 4.2 / yes / [5]
A2A-anta-03 / / 20.2 / yes / [5]
A2A-anta-04 / / 80 / yes / [5]
A2A-anta-05 / / 65 / yes / [5]
A2A-anta-06 / / 93 / yes / [11]
A2A-anta-07 / / 40 / yes / [6]
A2A-anta-08 / / 60 / yes / [6]
A2A-anta-09 / / 10 / yes / [6]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A2A-anta-10 / / 20 / yes / [6]
A2A-anta-11 / / 20 / yes / [6]
A2A-anta-12 / / 70 / yes / [6]
A2A-anta-13 / / 100 / yes / [6]
A2A-anta-14 / / 20 / yes / [6]
A2A-anta-15 / / 23 / yes / [7]
A2A-anta-16 / / 110 / yes / [1]
A2A-anta-17 / / 100 / yes / [1]
A2A-anta-18 / / 21 / yes / [1]
A2A-anta-19 / / 0.12 / yes / [1]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A2A-anta-20 / / 0.19 / yes / [1]
A2A-anta-21 / / 5.48 / yes / [2]
A2A-anta-22 / / 1 / yes / [2]
A2A-anta-23 / / 4 / yes / [2]
A2A-anta-24 / / 0.43 / yes / [2]
A2A-anta-25 / / 114 / yes / [8]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A2A-agon-01 / / 22 (rat) / no / [13]
A2A-agon-02 / / 462 (rat) / no / [13]
A2A-agon-03 / / 620 / no / [13]
A2A-agon-04 / / 330 (rat) / no / [13]
A2A-agon-05 / / 12 (rat) / no / [13]
A2A-agon-06 / / 20 / no / [14]
A2A-agon-07 / / 153 / no / [14]
A2A-agon-08 / / 27 / no / [14]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A2A-agon-09 / / 270 / no / [14]
A2A-agon-10 / / 290 / no / [14]
A1-anta-01 / / 70 / yes / [15]
A1-anta-02 / / 4.3 / yes / [16]
A1-anta-03 / / 7.8 / no / [16]
A1-anta-04 / / 4.3 / no / [16]
A1-anta-05 / / 1.6 / no / [16]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A1-anta-06 / / 14.9 / no / [16]
A1-anta-07 / / 0.6 / no / [16]
A1-anta-08 / / 629 / no / [17]
A1-anta-09 / / 22 / no / [18]
A1-anta-10 / / 2646 / no / [19]
A1-agon-01 / / 15 / no / [20]
A1-agon-02 / / 1.2 / no / [20]
A1-agon-03 / / 0.83 / no / [14]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A1-agon-04 / / 4.7 / no / [20]
A1-agon-05 / / 2.6 / no / [20]
A1-agon-06 / / 6.5 / yes / [14]
A1-agon-07 / / 23 / yes / [14]
A1-agon-08 / / 7.8 / no / [21]
A1-agon-09 / / 5.1 / no / [14]
A1-agon-10 / / 3.1 / no / [14]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A2B-anta-01 / / 31 / yes / [22]
A2B-anta-02 / / 197 / yes / [22]
A2B-anta-03 / / 12 / yes / [23]
A2B-anta-04 / / 169 / yes / [22]
A2B-anta-05 / / 159 / yes / [22]
A2B-anta-06 / / 288 / no / [24]
A2B-anta-07 / / 457 / no / [24]
A2B-anta-08 / / 2239 / no / [24]
A2B-anta-09 / / 64 / no / [24]
A2B-anta-10 / / 2.6 / no / [24]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A2B-agon-01 / / 7.3 / no / [25]
A2B-agon-02 / / 15.2 / no / [25]
A2B-agon-03 / / 12.3 / no / [25]
A2B-agon-04 / / 10.5 / no / [25]
A2B-agon-05 / / 32.4 / no / [25]
A2B-agon-06 / / 45.4 / no / [25]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A2B-agon-07 / / 53.6 / no / [25]
A2B-agon-08 / / 42.6 / no / [25]
A2B-agon-09 / / 360 / no / [25]
A2B-agon-10 / / 31.6 / no / [25]
A3-anta-01 / / 0.25 / no / [26]
A3-anta-02 / / 0.41 / no / [26]
A3-anta-03 / / 0.61 / no / [26]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A3-anta-04 / / 5 / no / [26]
A3-anta-05 / / 0.9 / no / [26]
A3-anta-06 / / 15 / no / [26]
A3-anta-07 / / 5.4 / no / [26]
A3-anta-08 / / 26 / no / [26]
A3-anta-09 / / 28 / no / [26]
A3-anta-10 / / 45 / no / [26]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A3-agon-01 / / 1.8 / no / [14]
A3-agon-02 / / 1.4 / no / [14]
A3-agon-03 / / 0.38 / no / [14]
A3-agon-04 / / 5.8 / no / [14]
A3-agon-05 / / 1.9 / no / [27]
A3-agon-06 / / 0.33 / no / [27]
A3-agon-07 / / 0.43 / no / [27]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
A3-agon-08 / / 0.40 / no / [27]
A3-agon-09 / / 2.5 / no / [27]
A3-agon-10 / / 1.9 / no / [27]
Delta-opioid-anta-01 / / 27 / no / [28]
Delta-opioid-anta-02 / / 0.7 / no / [28]
Delta-opioid-anta-03 / / 9 / no / [28]
Delta-opioid-anta-04 / / 322 / no / [29]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
Delta-opioid-anta-05 / / 75 / no / [30]
Delta-opioid-anta-06 / / 88 / no / [30]
Delta-opioid-anta-07 / / 114 / no / [31]
Delta-opioid-anta-08 / / 39.7 / no / [31]
Delta-opioid-anta-09 / / 770 / no / [32]
Delta-opioid-anta-10 / / 90 / no / [32]
Delta-opioid-agon-01 / / 293 / no / [33]
Delta-opioid-agon-02 / / 1.2 / no / [34]
Delta-opioid-agon-03 / / 0.74 / no / [34]
Delta-opioid-agon-04 / / 48 / no / [34]
Table S2 continued…
Compound No / 2D Structure / Binding Affinity (Ki, nM) / Hits(yes or no) / Ref
Delta-opioid-agon-05 / / 15.1 / no / [35]
Delta-opioid-agon-06 / / 0.6 / no / [36]
Delta-opioid-agon-07 / / 0.3 / no / [36]
Delta-opioid-agon-08 / / 0.23 / no / [37]
Delta-opioid-agon-09 / / 3.5 / no / [37]
Delta-opioid-agon-10 / / 649 / no / [38]
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