Table 1:

Structure and Activity Relationship of Allosteric Hsp70 inhibitors

Compd	R1	R2	R3	MCF-7 IC50/μM	MDA-MB-231 IC50/μM	MEF IC50/μM
JG-98	5-Cl	ethyl	H	0.71 ± 0.22	0.39 ± 0.03	4.2 ± 1
1	5-Br	ethyl	H	0.44 ± 0.03	0.33 ± 0.04	6.1 ± 0.3
2	4-Br	ethyl	H	0.27 ± 0.03	0.11 ± 0.01	0.66 ± 0.04
3	5-NO2	ethyl	H	>5	4.8 ± 0.4	2.8 ± 0.1
4	4-SO2Me	ethyl	H	>5	>20	2.5 ± 0.6
5	5-CF3	ethyl	H	0.53 ± 0.11	0.36 ± 0.03	2.4 ± 0.2
6	4-OCF3	ethyl	H	0.26 ± 0.02	1.2 ± 0.1	0.34 ± 0.02
7	5-OCF3	ethyl	H	0.4 ± 0.04	0.8 ± 0.1	1.2 ± 0.1
8	4-Me	ethyl	H	0.21 ± 0.01	0.078 ± 0.01	1.3 ± 0.1
9 (JG-194)	5-Me	ethyl	H	0.16 ± 0.02	0.15 ± 0.01	1.9 ± 0.1
10	3-Me	ethyl	H	0.25 ± 0.02	0.21 ± 0.04	2.3 ± 0.2
11	6-Me	ethyl	H	0.29 ± 0.03	0.25 ± 0.03	1.6 ± 0.1
12	5-Ethyl	ethyl	H	0.080 ± 0.008	0.14 ± 0.01	1.0 ± 0.1
13	4-OCH3	ethyl	H	0.37 ± 0.02	0.36 ± 0.05	1.0 ± 0.1
14	5-OCH3	ethyl	H	0.13 ± 0.01	0.16 ± 0.01	2.0 ± 0.1
15	5-SCH3	ethyl	H	0.13 ± 0.01	0.12 ± 0.01	1.7 ± 0.1
16	5-Cl	allyl	H	0.17 ± 0.02	0.10 ± 0.01	2.4 ± 0.1
17	5-Cl	cyclopropyl	H	0.33 ± 0.03	0.56 ± 0.08	3.4 ± 0.2
18	5-Cl	3-methoxy-3- oxopropyl)	H	0.66 ± 0.07	0.24 ± 0.03	4.9 ± 0.3
19	5-Cl	ethyl	o-F	0.16 ± 0.02	0.29 ± 0.04	1.2 ± 0.1
20	5-Cl	ethyl	m-F	0.48 ± 0.04	1.0 ± 0.2	1.0 ± 0.1
21	5-Cl	ethyl	p-F	0.61 ± 0.03	1.1 ± 0.2	1.9 ± 0.1
22	5-Cl	ethyl	o-Cl	0.19 ± 0.01	0.18 ± 0.02	0.70 ± 0.03
23	5-Cl	ethyl	m-Cl	0.26 ± 0.02	0.51 ± 0.06	0.69 ± 0.03
24	5-Cl	ethyl	p- Cl	1.45 ± 0.13	0.41 ± 0.06	3.1 ± 0.3
25	5-Cl	ethyl	o-CF3	0.13 ± 0.02	0.13 ± 0.01	1.2 ± 0.1
26	5-Cl	ethyl	o-Br	0.19 ± 0.01	0.20 ± 0.03	1.6 ± 0.1
27	5-Cl	ethyl	o-methoxy carbonyl	0.17 ± 0.02	0.17 ± 0.02	2.9 ± 0.1
28	5-Cl	ethyl	o-CH3	0.19 ± 0.01	0.20 ± 0.03	1.6 ± 0.1
29	5-Cl	ethyl	o-OCH3	0.40 ± 0.03	0.12 ± 0.01	1.5 ± 0.1
30	5-Cl	ethyl	o-SCF3	0.13 ± 0.01	0.16 ± 0.01	3.7 ± 0.2
31	5-Cl	ethyl	o-OCF3	0.22 ± 0.01	0.12 ± 0.009	2.7 ± 0.1
32(JG-258)	-	-	-	> 5	> 20	> 20