Figure 1.
Some adamantyl derivatives with antiinflamatory and analgesic properties.
Figure 2.
Adamantyl analogues of paracetamol.
Figure 3.
Reagents and conditions: i) acetic anhydride, water, 0°C−rt.
Figure 4.
Synthesis of compounds 6a and 6b.
Reagents and conditions: i) (i) S-α-methylbenzylamine, EtOH, reflux, 2 days; (ii) H2, 10% Pd-C, THF, rt; 12 h; (iii) acetic anhydride, water, 0°C−rt.
Figure 5.
Analgesic activity of compounds 5 and 6a/b in comparison with paracetamol and morphine.
Bars show the mean number of stretches induced by acetic acid (i.p., 2%) in mice treated with paracetamol (100, 200 mg/kg), morphine (5 mg/kg), compound 5 (100, 200 or 500 mg/kg), or compound 6a/b (250, 375, 500 and 750 mg/kg). Data are given as mean ± SEM, with n = 15, and (* p<0.05, ** p<0.01 One way ANOVA to compare with control group.
Figure 6.
Functional expression of the TRP channels in the cell lines.
Fluorescence time course for cells treated with TRP antagonists (squares) or agonist (circle). TRP-mediated Ca2+ influx was observed upon addition of agonist in the seven cycle, while the addition of the antagonist (squares) antagonized this response. The effect of the compound 6a/b at 50 µM is shown (triangles). TRPA1 was activated with 100 µM AITC, TRPV1 was activated by 10 µM capsaicin and TRPM8 was activated with 100 µM menthol. Ruthenium red (RR) was at 10 µM, and AMTB was used at 100 µM.
Figure 7.
Fluorometric Ca2+ assay of thermoTRP channels to evaluate the inhibitory activity of compound 6a/b.
a) Activity of compound 6a/b at 50 µM on TRPA1, TRPV1 and TRPM8. b) Dose-response curve for TRPA1 inhibition by compound 6a/b. Solid lines depict the best fit to a binding isotherm, with IC50 = 2.6±1.1 µM, and nH (hill coefficient) = 0.21. TRPA1 was activated with 100 µM AITC, TRPV1 was activated by 10 µM capsaicin and TRPM8 was activated with 100 µM menthol. Data are given as mean ± SEM, with n (number of experiments) ≥5.