TY - JOUR
T1 - Semi-synthesis of novel buprenorphine derivatives and their anti-nociceptive properties and dependency potential
AU - Hasanpour, Zahra
AU - Salehi, Peyman
AU - Bunch, Lennart
AU - Khoramjouy, Mona
AU - Bararjanian, Morteza
AU - Stærk, Dan
AU - Faizi, Mehrdad
PY - 2021
Y1 - 2021
N2 - Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with ED50 equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with ED50 of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects of these. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared to morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine
AB - Novel 1,2,3-triazole-tethered N-norbuprenorphine derivatives with an OMe or OH group at the C3 position were synthesized alongside with evaluation of their analgesic properties. The analgesic activities of the resulting library were investigated via tail flick test in mice. Our results indicated that 10b and 10e were as effective as the starting compounds 8 and 9 with ED50 equal to 16.59 and 19.44 mg/kg, respectively. To investigate the effect of a methyl group at C3 on biological properties, the most active compounds were O-demethylated and their anti-nociceptive effects were assessed. The new O-demethylated derivatives (11b and 11e) showed better analgesic properties than the parent compounds with ED50 of 14.73 and 15.80 mg/kg, respectively. Naloxone prevented the analgesic effect of the synthesized compounds, indicating that the opioid receptors are highly involved in the anti-nociceptive effects of these. The potential dependency effects of the most potent derivatives were studied by condition place preference test in mice and compared to morphine and buprenorphine. Interestingly, 10b, 10e, 11b, and 11e did not show any dependency effect, similar to buprenorphine
U2 - 10.1139/cjc-2020-0429
DO - 10.1139/cjc-2020-0429
M3 - Journal article
VL - 99
SP - 910
EP - 919
JO - Canadian Journal of Chemistry
JF - Canadian Journal of Chemistry
SN - 0008-4042
IS - 11
ER -