Table 7SAR analysis of additional P2 derivatives for NS3 helicase inhibitor discovery

Compound ID
Image ml283fu10.jpg

structure, R =
target potency, MBHA (IC50, avg, μM)cell-based assaysantitarget potency (IC50, avg, μM)
#CID*1b(con1)replicon (% inhibition @ 10 μM)cell viability (% @ 10 μM)FID (SG)
%Displaced @ 100 μM
SSB
%Displaced @ 100 μM
SID2a(JFH1)EC50 (μM)SSB
EC50 (μM)
3449849293S
Image ml283fu11.jpg
2.7 ± 0.7
3.6 ± 0.0
61 ± 10
21 ± 33
87 ± 4
99 ± 11
64 ± 7
63 ± 11
83
78
104178063
123050377
2.3 ± 0.6
4.4 ± 0.7
36 ± 25
25 ± 36
22 ± 4
28 ± 9
3552914816S
Image ml283fu12.jpg
14.4 ± 0.0424 ± 32101 ± 935 ± 23105
12305037813.5 ± 0.6>1009 ± 2
3653308659S
Image ml283fu13.jpg
4.5 ± 0.4−9 ± 8103 ± 580 ± 394
1247678643.9 ± 0.330 ± 49 ± 2
3750930738S
Image ml283fu14.jpg
3.6 ± 115 ± 11114 ± 1359 ± 17nd
1142795986.4 ± 346 ± 36nd
3849849289S
Image ml283fu15.jpg
5.5 ± 2.137 ± 485 ± 259 ± 495
1041780673.5 ± 1.268 ± 25±
3949849287
46897855
S
Image ml283fu16.jpg
29 ± 31
4.0 ± 2.4
44 ± 9
42 ± 5
95 ± 3
90 ± 4
nd
67 ± 5
nd
95
99350539
104178065
>100
1.9 ± 0.9
nd
22 ± 4
nd
5 ± 1
4050930756S
Image ml283fu17.jpg
22.1 ± 251 ± 22113 ± 615 ± 1048
11427959248 ± 40>100>100
4150930734S
Image ml283fu18.jpg
52 ± 2059 ± 13117 ± 519 ± 763
11427959352 ± 25>10055 ± 20
4253239937S
Image ml283fu19.jpg
4.4 ± 0.348 ± 18102 ± 653 ± 2559
1243497404.6 ± 0.356 ± 400857 ± 16
4353312458S
Image ml283fu20.jpg
11.0 ± 1.6−64 ± 25109 ± 892 ± 4102
12477194413.5 ± 0.727 ± 35 ± 1
4453255450S
Image ml283fu21.jpg
>10026 ± 21102 ± 948 ± 589
124391240>100>10017 ± 4
4553356772S
Image ml283fu22.jpg
4.1 ± 1.3−18 ± 56108 ± 446 ± 295
1252588586.0 ± 1.9>1006 ± 1
4649849298S
Image ml283fu23.jpg
5.3 ± 0.943 ± 993 ± 190 ± 996
1041780534.0 ± 1.918 ± 610 ± 3
4753255447S
Image ml283fu24.jpg
5.1 ± 3.37 ± 3999 ± 784 ± 2291
1243912414.0 ± 1.318 ± 1315 ± 3
4853356770S
Image ml283fu25.jpg
7.8 ± 2.217 ± 2593 258 ± 3100
1252588569.9 ± 3.474 ± 711 ± 2
4953356653S
Image ml283fu26.jpg
3.6 ± 0.935 ± 2898 ± 174 ± 494
1252586654.4 ± 0.48 ± 25 ± 1
5053356656S
Image ml283fu27.jpg
4.8 ± 221 ± 1099 ± 955 ± 695
1252586676.4 ± 2.573 ± 134 ± 1
5153356771S
Image ml283fu28.jpg
9.3 ± 3.89 ± 998 ± 1076 ± 998
1252588579.6 ± 3.130 ± 37 ± 1
5249849295S
Image ml283fu29.jpg
24.4 ± 2.244 ± 575 ± 369 ± 498
10417805613.4 ± 7.242 ± 610 ± 2
5353255448S
Image ml283fu30.jpg
32.0 ± 16−7 ± 14101 ± 657 ± 20nd
12439123735.0 ± 6.182 ± 34nd
*

Denotes whether the compound was synthesized (S) or purchased (P).

See Figure 16 for general compound structure. All the compounds are ammonium salts except entries 35, 38, 43 and 52.

From: Hepatitis C Virus NS3 Helicase Inhibitor Discovery

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Probe Reports from the NIH Molecular Libraries Program [Internet].

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