A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model
Table 5
These ligands bound with potent affinity for α1; ligands bound with values <20 nM at this subtype.
Cook code
WY-TSC-4 (WYS8)
0.007
0.99
1.63
51.04
SH-TSC-2 (BCCT)
0.03
0.0419
0.035
69.32
QH-II-090 (CGS-8216)
0.05
0.08
0.12
0.25
17
XLI-286
0.051
0.064
0.118
0.684
QH-II-077
0.06
0.08
0.05
0.12
4
QH-II-092
0.07
0.03
0.04
ND
0.17
ND
JYI-57
0.076
0.076
0.131
ND
0.036
ND
QH-II-085
0.08
0.06
0.02
ND
0.08
ND
XHE-II-024
0.09
0.18
0.32
14
0.24
11
PWZ-007A
0.11
0.1
0.09
ND
0.2
10
CGS8216
0.13
ND
ND
ND
ND
46
SPH-121
0.14
1.19
1.72
ND
4
479
QH-II-075
0.18
0.21
0.25
ND
1.3
40
PZII-028
0.2
ND
0.2
ND
0.32
1.9
CGS9895
0.21
ND
ND
ND
ND
9.3
PWZ-0071
0.23
0.17
0.12
ND
0.44
17.31
XHE-III-24
0.25
ND
8
222
10
328
JYI-42
0.257
0.146
0.278
ND
0.256
ND
CGS9896
0.28
ND
ND
ND
ND
181
JYI-64 (C17H12N4FBr)
0.305
1.111
0.62
ND
0.87
5000
PZII-029
0.34
ND
0.79
ND
0.52
10
BRETAZENIL
0.35
0.64
0.2
ND
0.5
12.7
FG8205
0.4
2.08
1.16
ND
1.54
227
YT-5
0.421
0.6034
36.06
ND
1.695
ND
6-PBC
0.49
1.21
2.2
ND
2.39
1343
QH-146
0.49
ND
0.76
ND
7.7
10000
DM-II-90 (C17H12N4BrCl)
0.505
1
0.63
ND
0.37
5000
SPH-165
0.63
2.79
4.85
ND
10.4
1150
BCCt
0.72
15
18.9
ND
110.8
5000
SH-I-048A
0.774
0.1723
0.383
ND
0.11
ND
alprazolam
0.8
0.59
1.43
ND
1.54
10000
Ro15-1788
0.8
0.9
1.05
ND
0.6
148
WYS10 C14H9F3N2O2
0.88
36
25.6
ND
548.7
15.3
WY-B-15
0.92
0.83
0.58
2080
4.42
646
WY-A-99-2 (WYS8)
0.972
111
102
2000
208
1980
XHE-III-06a
1
2
1
5
1.8
37
Xli366 C22H21N3O2
1
ND
ND
ND
ND
ND
JYI-59 (C22H13N3O2F4)
1.08
2.6
11.82
ND
11.5
5000
WYSC1 C16H16N2O2
1.094
5.44
12.3
ND
69.8
21.2
MLT-I-70
1.1
1.2
1.1
ND
40.3
1000
SVO-8-30
1.1
5.3
5.3
2.8
0.6
15
BCCE
1.2
4.9
5.7
ND
26.8
2700
XHE-III-04
1.2
2
1.1
219
0.4
500
XLi350 C17H11ClN2O
1.224
1.188
ND
ND
2.9
ND
XHE-III-49
1.3
5.5
4.2
38.7
11.3
85.1
PWZ-009A1
1.34
1.31
1.26
ND
0.84
2.03
DM-239
1.5
ND
0.53
ND
0.14
6.89
XLi351 C21H21ClN2OSi
1.507
0.967
ND
ND
1.985
ND
XLi352 C18H13ClN2O
1.56
0.991
ND
ND
1.957
ND
TG-4-39
1.6
34
24
5.6
1.4
23
TG-II-82
1.6
2.9
2.8
ND
1
1000
CM-A87
1.62
4.54
14.73
1000
4.61
1000
QH-II-082
1.7
1.8
1.6
ND
6.1
100
JYI-49 (C20H12N3O2F4Br)
1.87
2.38
ND
ND
6.7
3390
LJD-III-15E
1.93
14
19
ND
70.8
1000
SPH-38
2
5.4
10.8
ND
18.5
3000
XHE-I-093
2
7.1
8.9
1107
20
1162
MSA-IV-35
2.1
16
21
ND
995
3000
JYI-19 (C23H23N3O3S)
2.176
205
ND
ND
34
12.7
FLUNITRAZEPAM
2.2
2.5
4.5
ND
2.1
2000
YCT-5
2.2
11.46
16.3
ND
200
10000
TJH-IV-51
2.39
17.4
14.5
ND
316
10000
WYS13 C20H18N2O3
2.442
13
27.5
ND
163
5000
YT-III-25
2.531
5.786
5.691
ND
0.095
ND
XHE-III-14
2.6
10
13
2
7
WYS9 C16H15IN2O2
2.72
22.2
23.1
ND
562
122
JYI-47
2.759
2.282
0.511
ND
0.427
ND
CM-A82a
2.78
8.93
24.51
1000
7.49
1000
TG-4-29
2.8
3.9
2.7
2.1
0.18
3.9
XLi268 C17H13BrN4
2.8145
0.6862
ND
ND
0.6243
ND
JYI-54 (C24H15N3O3F4)
2.89
172
6.7
ND
57
1890
MMB-II-74
3
24.5
41.7
500
125.7
1000
MMB-III-016
3
1.97
2
1074
0.26
211
MMB-III-16
3
1.97
2
1074
0.26
211
QH-II-080b
3
3.7
4.7
ND
24
1000
YCT-7A
3
23.8
30.5
ND
240
10000
JYI-32 (C20H15N3O2BrF)
3.07
4.96
ND
ND
2.92
52.24
Ro15-4513
3.3
2.6
2.5
ND
0.26
3.8
XHE-II-017
3.3
10
7
258
17
294
XLi-JY-DMH ANX3
3.3
0.58
1.9
ND
4.4
5000
MLT-II-18
3.4
11.7
11
ND
225
10000
TJH-V-88
3.41
30
ND
140.9
10000
XLI-2TC
3.442
1.673
44.08
ND
1.121
WYS15 C22H20N2O2
3.63
2.02
44.3
ND
76.5
5000
CM-A57
3.7
27
40
ND
254
1000
XHE-II-006b
3.7
15
12
1897
144
1000
JYI-60
3.73
1.635
4.3
ND
1.7
5000
RY-008
3.75
7.2
4.14
ND
1.11
44.3
MLT-II-18
3.9
12.2
24.4
ND
210
10000
OMB-18
3.9
1.2
3.4
1733
0.8
5
WY-B-09-1
3.99
8
32
1000
461
2000
SHU-1-19
4
12
7
48
14
84
ZK 93423
4.1
4.2
6
ND
4.5
1000
WY-B-23-2 (WYS11)
4.2
37.7
39
2000
176
69.4
WY-B-23-2 (WYS11)
4.2
37.7
73
ND
176
69.4
WY-B-99-1
4.4
4.5
5.58
2000
47
2000
WY-B-26-2
4.45
44.57
42.66
2000
124
2000
XHE-II-006a
4.7
4.4
20
1876
89
3531
CM-B01
4.8
31
34
1000
286
1000
PWZ-085
4.86
13
8.5
ND
0.55
40
MLT-II-16
5.05
10.41
18.4
ND
260
10000
3 PBC
5.3
52.3
68.8
ND
591
1000
MA-3-PROPOXYL
5.3
52.3
68.8
ND
591
1000
TJH-IV-43
5.42
30.19
48.9
ND
475
10000
DMCM
5.69
8.29
4
ND
1.04
134
DM-139
5.8
ND
169
ND
9.25
325
XHE-II-073A (R ENRICHED)
5.9
11
10
15
1.18
140
MSR-I-032
6.2
18.7
4
ND
3.3
74.9
JYI-70 (C19H13N4F)
6.3
2.1
ND
ND
0.56
5000
XLi343 C20H19ClN2OSi
6.375
17.71
ND
ND
150.5
ND
3 EBC
6.43
25.1
28.2
ND
826
1000
DM-146
6.44
ND
148
ND
4.23
247
DM-215
6.74
ND
7.42
ND
0.293
8.28
ZG69A
6.8
16.3
9.2
ND
0.85
54.6
ZG-69a (Ro15-1310)
6.8
16.3
9.2
ND
0.85
54.6
WY-B-14 (WYS7)
6.84
30
36
2000
108
1000
YT-II
6.932
0.8712
3.518
ND
5.119
ND
SVO-8-67
7
41
26
15
2.3
191
MLT-II-34
7.04
15.95
22.3
ND
158
1000
SPH-195
7.2
168.5
283.5
ND
271
10000
XHE-I-065
7.2
17
18
500
57
500
ZG-234
7.25
22.14
9.84
ND
0.3
5.25
SH-I-04
7.3
6.136
5.1
ND
7.664
ND
XHE-I-038
7.3
5
34
ND
132
1000
XHE-III-13
7.3
ND
7.1
880
1.6
311
WY-B-25
7.6
40
66
2000
263
2000
CM-A49 (R)
7.7
32.5
43
ND
69
1000
SVO-8-14
8
25
8
6.9
0.9
14
TG-4-29
8.3
10.2
6.9
ND
0.4
7.61
XHE-II-002
8.3
18
13
3.9
1.5
11
WY-B-14 (WYS7)
8.5
165
245
ND
1786
5000
XHE-II-011
9
60
39
3233
90
1000
WY-B-27-2
9.19
111
72
2000
449
2000
QH-II-063
9.4
9.3
31
ND
7.7
3000
JC184 C13H9BrN2OS
9.606
10.5
ND
ND
6.709
ND
ZG-208
9.7
11.2
10.9
ND
0.38
4.6
RY-I-31
10
45
19
ND
6
1000
WY-B-23-1
10
33
43
1000
189
2000
RY-098
10.1
22.2
16.5
ND
1.68
100
Hz148 C18H15N3
10.98
5000
ND
ND
256
5000
SVO-8-20
11
40
28
19
8.6
138
XHE-II-073B (S-ENRICHED)
11
17
12
33
2.1
269
SH-I-085
11.08
4.866
13.75
ND
0.24
ND
PWZ-096
11.1
36
16.9
ND
1.07
51.5
ZG-168
11.2
10.7
9.2
ND
0.47
9.4
CM-A77
11.51
51.9
105.16
1000
42.62
1000
WY-B-20
12
39
47
2000
122
3000
ABECARNIL
12.4
15.3
7.5
ND
6
1000
SH-I-89S
12.78
8.562
8.145
ND
3.23
ND
ZG-213
12.8
49.8
30.2
ND
3.5
22.5
EDC-I-071
12.9
83.1
ND
ND
314
5000
MMB-III-14
13
13
6.9
333
1.1
333
DM-173
13.1
ND
38.1
ND
0.78
118
XLI-348
13.56
11.17
1.578
ND
82.05
ND
EDC-I-093
13.6
423
ND
ND
2912
5000
diazepam
14
20
15
ND
11
ND
XLi223 C22H20BrN3O2
14
8.7
18
1000
10
2000
WYSC2 C15H11F3N2O2
14.14
113
170
ND
518
61.2
SH-I-030
14.42
11.04
19.09
ND
1.89
ND
CM-A100
14.49
44.91
123.8
1000
65.31
1000
RY-033
14.8
56
25.3
ND
1.72
22.9
HJ-I-037
15.07
8.127
28.29
ND
0.818
ND
YT-6
15.31
87.8
60.49
ND
1.039
ND
EDC-II-044
15.4
ND
293
ND
323
1000
CM-A58
16
120
184
ND
1000
1012
QH-II-067a
16
31
52
ND
199
3000
CD-214
16.4
48.2
42.5
ND
9.8
168
JYI-06 (C23H23N3O4)
16.5
5.48
5000
ND
12.6
5000
CM-A50 (S)
17
59
88
ND
144
1000
RY-061
17
13
6.7
ND
0.3
31
ZG-224
17.1
33.7
50
ND
2.5
30.7
ZG-63A
17.3
21.6
29.1
ND
0.65
4
DM-II-30 (C20H13N3O2BrF3)
17.6
13.4
28.51
ND
7.8
5000
CM-A64
18
60
116
ND
216
1000
RY-071
19
56
91
ND
7.2
266
WZ-113
19.2
13.2
13.4
ND
11.5
300
YT-III-23
19.83
23.65
19.87
ND
1.105
ND
CM-E09b
20
22
19
55
0.45
69
MMB-II-90
20
24
5.7
9
0.25
36
Affinity of compounds at /BzR recombinant subtypes was measured by competition for [3H]flunitrazepam or [3H] Ro15-4513 binding to HEK cell membranes expressing human receptors of compositions 132, 232, 332, 432, 532, and 632 [139]. Data represent the average of at least three determinations with a SEM of ±5%. The structures of these ligands are in the Ph.D. thesis of Clayton (2011) [22] and Supporting Information.
