Computational Study of Estrogen Receptor-Alpha Antagonist with Three-Dimensional Quantitative Structure-Activity Relationship, Support Vector Regression, and Linear Regression Methods
Table 1
Structures, experimental activities presented in IC50 and pIC50 values, and predicted pIC50 values by different modeling approaches.
1–54
55–68
No.
Substituents
IC50 (nM)
pIC50
Predicted
R
R′
CoMFA
CoMSIA
LR
SVM
1
H
H
300
6.52
7.17
6.72
6.88
6.39
2
H
4′-OH
35
7.46
7.33
6.98
7.71
7.46
3*
H
4′-OMe
100
7.00
7.12
6.74
7.00
6.70
4
6-C≡CH
4′-OH
20
7.70
7.64
7.03
7.23
7.15
5*
6-CO2Me
4′-OH
30
7.52
7.18
6.83
6.17
6.58
6
6-COMe
4′-OH
60
7.22
7.28
7.49
6.81
6.72
7
6-OMe
4′-OH
250
6.60
6.83
7.02
7.38
7.38
8
6-Me
4′-OH
300
6.52
7.05
6.81
7.25
7.33
9**
6-Cl
4′-OH
1000
6.00
7.22
7.39
10
6-CONH2
4′-OH
1000
6.00
6.10
5.67
7.46
7.62
11
5-F, 6-OH
4′-OH
3
8.52
8.27
8.32
7.85
7.90
12
5-OH
4′-OH
100
7.00
7.03
6.45
7.15
7.22
13*
4,7-di(Me),6-OH
4′-OH
100
7.00
6.96
8.03
6.72
6.74
14
4-OH
4′-OH
190
6.72
6.68
6.16
7.14
6.89
15
7-OH
4′-OH
300
6.52
6.99
7.07
7.63
7.47
16
4,6-di(OH)
4′-OH
350
6.46
6.71
6.72
7.98
8.03
17
5,6-di(OH)
4′-OH
400
6.40
6.33
6.74
6.73
6.75
18
5,7-di(Me),6-OH
4′-OH
500
6.30
6.38
6.46
7.35
7.62
19
4,5-Benzo,6-OH
4′-OH
500
6.30
5.97
5.98
6.78
7.55
20
6-OMe
4′-OMe
300
6.52
6.56
6.82
6.61
6.30
21
5,6,7-tri(OMe)
4′-OMe
350
6.46
6.67
6.25
5.74
5.97
22
6-OMe
3′,4′-OCH2O
500
6.30
6.72
7.14
6.29
6.15
23
6-OMe
4′-CH2OH
600
6.22
5.87
5.86
6.68
6.40
24
6-OH
H
2.5
8.60
7.92
8.19
7.94
8.24
25*
6-OH
4′-OH
0.2
9.70
7.90
8.35
7.90
8.21
26
6-OH
4′-C≡CH
0.8
9.10
7.83
8.11
7.81
8.20
27
6-OH
4′-Cl
1
9.00
8.10
8.25
7.41
7.70
28
6-OH
4′-F
2.3
8.64
7.71
8.26
8.08
8.19
29
6-OH
4′-Et
5
8.30
7.81
7.84
7.86
7.94
30
6-OH
4′-CH=CH2
7
8.15
7.43
7.97
7.77
7.84
31
6-OH
4′-n-Bu
10
8.00
8.22
7.79
7.84
7.68
32*
6-OH
4′-i-Pr
30
7.52
7.81
7.76
7.65
7.62
33
6-OH
4′-Me
50
7.30
7.93
7.98
7.44
7.41
34
6-OH
4′-Ph
100
7.00
7.25
7.72
6.80
7.04
35
6-OH
4′-CH2SEt
100
7.00
7.25
7.30
7.49
7.06
36
6-OH
4′-NO2
500
6.30
6.65
6.36
6.80
6.55
37**
6-OH
4′-OMe
1000
6.00
7.83
7.97
38*
6-OH
4′-CONMe2
20
7.70
7.72
7.20
6.67
7.43
39
6-OH
4′-COMe
32
7.49
7.19
7.82
6.95
7.02
40
6-OH
4′-CON(H)Me
40
7.40
6.87
7.29
7.12
7.89
41*
6-OH
4′-CO2Me
50
7.30
7.23
7.33
7.03
6.79
42
6-OH
4′-CO2Et
50
7.30
7.16
7.30
7.77
7.67
43
6-OH
4′-CONH2
200
6.70
6.95
7.18
7.42
7.78
44
6-OH
4′-CO2H
325
6.49
7.08
6.78
6.92
6.79
45
6-OH
3′-F, 4′-OH
0.3
9.52
9.10
8.78
8.47
8.30
46
6-OH
2′-Me
0.7
9.15
8.85
8.37
8.20
8.25
47
6-OH
3′-Me, 4′-OH
1
9.00
9.31
9.03
8.41
8.39
48
6-OH
2′-Me, 4′-OH
2
8.70
9.29
9.05
8.46
8.40
49
6-OH
2′-OMe, 4′-OH
2
8.70
8.66
8.81
9.65
9.73
50
6-OH
3′-Cl, 4′-OH
2.3
8.64
8.98
9.17
8.55
9.01
51
6-OH
3′-F
2.5
8.60
8.36
8.52
8.51
8.57
52
6-OH
3′-OH
3.2
8.49
8.39
8.39
8.32
8.29
53
6-OH
2′-OH
10
8.00
8.55
8.39
8.41
8.39
54
6-OH
3′,5′-Di(Me), 4′-OH
100
7.00
6.98
7.27
6.58
6.01
55
6-OH
1′-Naphthyl
0.8
9.10
9.39
8.70
8.74
8.17
56
6-OH
4′-OH-1′-Naphthyl
2
8.70
8.74
8.70
8.60
8.35
57
6-OH
trans-4′-OH-Cyclohexyl
2
8.70
8.76
8.46
8.28
8.71
58
6-OH
Cyclohexyl
2.5
8.60
8.66
8.47
9.00
9.34
59
6-OH
Isopropyl
3
8.52
8.32
8.48
7.85
7.26
60
6-OH
Cyclopentyl
5
8.30
8.47
8.48
8.10
7.80
61*
6-OH
4′-Hydroxybenzyl
5
8.30
8.57
8.56
8.41
8.15
62*
6-OH
3′-Thienyl
10
8.00
7.70
8.32
7.47
7.35
63
6-OH
2′-Thienyl
20
7.70
7.64
7.96
7.19
7.24
64*
6-OH
Ethyl
20
7.70
7.88
8.48
8.00
8.36
65
6-OH
Methyl
35
7.46
7.30
8.26
7.16
6.68
66
6-OH
2′-Naphthyl
80
7.10
7.09
6.95
8.81
8.70
67
6-OH
4′-Pyridyl
100
7.00
7.80
7.39
7.73
7.96
68
6-OH
4′-Pyridyl N-oxide
100
7.00
7.01
7.01
7.20
7.02
Compounds included in test set of CoMFA and CoMSIA modeling.
**Compounds not included in the training or test set of CoMFA and CoMSIA.
