Table 3.

Activity of orally administered A₃AR agonists (3 μmol/kg) in CCI model of neuropathic pain (mechanoallodynia) in mice and physicochemical parameters.

Compound	Max. effect Emax (%±SEM)a	Effect at 3h (%±SEM)	n	MW (D)	cLogPb	tPSA (Å2)
1	100 ± 0.0	23.7 ± 10.8	4	565	4.15	122
2	93.3 ± 6.7	82.8 ± 11.2	4	459	2.17	122
4	94.3 ± 5.7	78.1 ± 3.5	4	526	1.42	122
5	77.4±4.5	27.5±4.1	4	461	1.58	150
6	69.1±8.6	7.9±7.9	2	496	2.04	150
7	75.2±12.8	27.0±7.4	4	497	1.79	150
8	60.9±11.9	21.1±3.3	4	462	0.29	162
9	92.7±9.8	36.2±6.8	4	463	-0.67	175
10	76.6±0.9	26.6±6.3	4	463	-0.67	175
11	82.5±5.9	19.1±5.9	4	465	-0.31	165
12	65.3±8.2	21.1±7.0	2	451	0.96	159
13	74.0±10.7	22.3±8.3	4	502	2.34	159
14	66.8±19.4	8.4±7.2	2	502	2.19	150
15	84.9±14.0	17.9±12.6	4	515	2.72	150
16	90.7±6.0	85.2±9.0 4	4	542	3.10	150
17	94.7±3.1	91.0±4.5 4	4	612	4.35	150
18	94.1±5.9	82.9±5.3 2	2	592	4.29	150
19	69.1±8.6	13.5±2.3	2	546	2.34	150
20	94.1±5.9	22.4±6.6	2	569	1.22	165

^aPercent represents reversal of reduction in PWT of the ipsilateral hind paw. The time of peak for compounds 5 – 20 is 1 h. Data for 1, 2 and 4 are from Tosh et al.⁸ No mechano-allodynia or A₃AR agonist effect on PWT was observed on the contralateral side.

^bcalculated using ChemBioDraw, v. 14.0.