Supplementary Material

1 Structure-Activity Relationships (SARs) of the thieno[2,3-c]pyridine, RX-111

Comp. / R1 / R2 / N-(R3)(R4) / R5-R8 / % Inhibition at 30 M / IC-50
[M]
1 / CH(CH3)2 / C(O)NH2 / tetrahydro-isoquinoline / H / 13±3
2 / CH3 / benzothiazol-2-yl / CH2CH3; CH2CH3 / H / 60±10
3 / CH(CH3)2 / benzothiazol-2-yl / CH2CH3; CH2CH3 / H / 10±2
4 / CH3 / benzothiazol-2-yl / CH2CH2OCH3; CH2CH2OCH3 / H / 43±8
5 / CH2CH3 / benzothiazol-2-yl / CH2CH3; CH2CH2CH2CH3 / H / 62±8
6 / CH3 / benzothiazol-2-yl / CH3; C6H5 / H / 44±7
7 / CH3 / benzothiazol-2-yl / ethyl piperazine-1-carboxylate / H / 19±3
8 / CH2CH3 / benzothiazol-2-yl / azepane / H / 46±6
9 / CH3 / benzothiazol-2-yl / morpholine / H / 52±9
10 / CH(CH3)2 / benzothiazol-2-yl / morpholine / H / 25±6
11 / CH2CH3 / benzothiazol-2-yl / CH2CH3; CH2CH3 / H / 0.35±0.1
12 / CH(CH3)2 / C(O)NH2 / CH2CH3; CH2CH2CH2CH3 / H / 55±9
13 / CH(CH3)2 / C(O)NH2 / CH3; C6H5 / H / 68±11
14 / CH(CH3)2 / C(O)NH2 / 3,5-dimethylpiperidine / H / 35±9
15 / CH(CH3)2 / C(O)OCH2CH3 / CH3; CH2CH2CH2CH3 / H / 40±9
16 / CH(CH3)2 / C(O)OCH2CH3 / tetrahydroquinoline / H / 11±2
17 / CH(CH3)2 / C(O)OCH2CH3 / ethyl piperazine-1-carboxylate / H / 21±4
18 / H / C(O)OCH2CH3 / azepane / CH3 / 11±3
19 / H / C(O)OCH3 / CH2CHCH3; CH2CHCH3 / CH3 / 43±9
20 / H / C(O)OCH2CH3 / CH2CH3; CH2CH3 / CH3 / 26±6
21 / H / C(O)NH2 / CH3; C6H11 / CH3 / 36±7
22 / H / C(O)NH2 / CH2CH3; CH2CH3 / CH3 / 35±6
23 / H / C(O)NH2 / CH3; CH2CH2CH2CH3 / CH3 / 39±6
24 / H / C(O)NH2 / ethyl piperazine-1-carboxylate / CH3 / 29±5
25 / H / C(O)NH2 / tetrahydroquinoline / CH3 / 12±3
26 / H / C(O)NH2 / CH2CH2OCH3; CH2CH2OCH3 / CH3 / 23±5
27 / CH2CH3 / C(O)NHCH3 / CH3; C6H5 / H / 9±3
28 / CH2CH3 / C(O)NH2 / CH2CH3; CH2C6H5 / H / 63±9
29 / CH2CH3 / C(O)NH2 / 1-methylpiperazine / H / 30±5
30 / CH3 / benzothiazol-2-yl / CH2CH2CH3; CH2CH2CH3 / H / 21±3
31 / CH3 / benzothiazol-2-yl / CH2CH2CH2CH3; CH2CH2CH2CH3 / H / 27±4
32 / CH3 / benzothiazol-2-yl / CH3 ; CH2CH2CH2CH3 / H / 26±5
33 / CH3 / benzothiazol-2-yl / CH2CH3; CH2CH2CH2CH3 / H / 21±4
34 / CH3 / benzothiazol-2-yl / CH2CHCH3 ; CH2CHCH3 / H / 25±4
35 / CH3 / benzothiazol-2-yl / pyrrolidine / H / 24±5
36 / CH3 / benzothiazol-2-yl / piperidine / H / 26±3
37 / CH3 / benzothiazol-2-yl / 3-methylpiperidine / H / 23±3
38 / CH3 / benzothiazol-2-yl / 4-methylpiperidine / H / 33±4
39 / CH3 / benzothiazol-2-yl / 3,5-dimethylpiperidine / H / 24±5
40 / CH2CH3 / benzothiazol-2-yl / CH2CH2CH3; CH2CH2CH3 / H / 25±5
41 / CH2CH3 / benzothiazol-2-yl / CH2CHCH3 ; CH2CHCH3 / H / 25±4
42 / CH(CH3)2 / benzothiazol-2-yl / CH2CH3; CH2CH2CH2CH3 / H / 27±4
43 / CH(CH3)2 / benzothiazol-2-yl / CH2CHCH3 ; CH2CHCH3 / H / 17±3
44 / CH(CH3)2 / benzothiazol-2-yl / piperidine / H / 29±4
45 / CH(CH3)2 / benzothiazol-2-yl / 2-methylpiperidine / H / 24±5

2 Leukocyte adhesion to endothelial cells (video)

RX-111 inhibition of leukocyte adhesion to endothelial cells (video)

3 RX-111 in vivo activity – Inhibition of thioglycollate induced peritonitis

RX-111 dose-dependent inhibition of leukocyte infiltration in mouse peritonitis Thioglycollate peritonitis was induced in mice pre-treated with RX-111. RX-111 reduced inflammation, as measured by neutrophil count, in a dose-dependent manner (***p0.001; **p0.01).

4 RX-111 in vivoactivity – Inhibition of carrageenan-induced paw edema

Inhibition of acute inflammation in a mouse model of carrageenan induced edema byorally administered RX-111. Mice were treated orally with increasing concentrations of RX-111. Paw

edema was induced by carrageenan 60 minutes after RX-111 administration. RX-111 reduced

inflammation, as measured by paw thickness, in a dose dependent manner (***p0.001;

**p0.01,*p0.05)

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