TY  - JOUR
AU  - Vuckovic, S.
AU  - Prostran, M.
AU  - Ivanović, Milovan
AU  - Došen-Mićović, Ljiljana
AU  - Todorović, Zoran B.
AU  - Nesic, Z.
AU  - Stojanović, R.
AU  - Divac, N.
AU  - Mikovic, Z.
PY  - 2009
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/999
AB  - Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics. This study was aimed to review the structure-activity-relationship (SAR) of fentanyl analogs substituted in the position 3, or 4 of the piperidine ring. Pharmacological results show that the groups in position 3 of the piperidine ring, which are larger than methyl, severely reduce the analgesic potency compared to fentanyl. It is likely that the steric factor alone (i.e. voluminosity of the group and cis/trans isomerism), rather than the polarity and/or chemical reactivity, plays a crucial role in the analgesic potency of this series. Although the duration of action, in general, does not depend on the stereochemistry, longer action of the most potent 3-alkyl fentanyl analogs such as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by pharmacodynamic, rather than pharmacokinetic variables. Also, it is possible that the introduction of a functional group such as 3-carbomethoxy reduces the duration of action by altering pharmacokinetic properties. SAR findings obtained by evaluating the neurotoxic effects of fentanyl analogs substituted in the position 3 of the piperidine ring parallel the SAR findings on analgesia in regard to potency and duration of action. This might suggest that similar receptors are involved in producing both antinociceptive and neurotoxic effects of these drugs. It appears that both the potency and the duration of action in the series of fentanyl analogs substituted in position 4 of the piperidine ring is influenced only by the steric requirement and not by the chemical nature of the substituent.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Medicinal Chemistry
T1  - Fentanyl Analogs: Structure-Activity-Relationship Study
VL  - 16
IS  - 19
SP  - 2468
EP  - 2474
DO  - 10.2174/092986709788682074
ER  - 

@article{
author = "Vuckovic, S. and Prostran, M. and Ivanović, Milovan and Došen-Mićović, Ljiljana and Todorović, Zoran B. and Nesic, Z. and Stojanović, R. and Divac, N. and Mikovic, Z.",
year = "2009",
abstract = "Fentanyl is the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics. This study was aimed to review the structure-activity-relationship (SAR) of fentanyl analogs substituted in the position 3, or 4 of the piperidine ring. Pharmacological results show that the groups in position 3 of the piperidine ring, which are larger than methyl, severely reduce the analgesic potency compared to fentanyl. It is likely that the steric factor alone (i.e. voluminosity of the group and cis/trans isomerism), rather than the polarity and/or chemical reactivity, plays a crucial role in the analgesic potency of this series. Although the duration of action, in general, does not depend on the stereochemistry, longer action of the most potent 3-alkyl fentanyl analogs such as cis-3-methyl- and cis-3-ethyl fentanyl, is more likely influenced by pharmacodynamic, rather than pharmacokinetic variables. Also, it is possible that the introduction of a functional group such as 3-carbomethoxy reduces the duration of action by altering pharmacokinetic properties. SAR findings obtained by evaluating the neurotoxic effects of fentanyl analogs substituted in the position 3 of the piperidine ring parallel the SAR findings on analgesia in regard to potency and duration of action. This might suggest that similar receptors are involved in producing both antinociceptive and neurotoxic effects of these drugs. It appears that both the potency and the duration of action in the series of fentanyl analogs substituted in position 4 of the piperidine ring is influenced only by the steric requirement and not by the chemical nature of the substituent.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Medicinal Chemistry",
title = "Fentanyl Analogs: Structure-Activity-Relationship Study",
volume = "16",
number = "19",
pages = "2468-2474",
doi = "10.2174/092986709788682074"
}

Vuckovic, S., Prostran, M., Ivanović, M., Došen-Mićović, L., Todorović, Z. B., Nesic, Z., Stojanović, R., Divac, N.,& Mikovic, Z.. (2009). Fentanyl Analogs: Structure-Activity-Relationship Study. in Current Medicinal Chemistry
Bentham Science Publ Ltd, Sharjah., 16(19), 2468-2474.
https://doi.org/10.2174/092986709788682074

Vuckovic S, Prostran M, Ivanović M, Došen-Mićović L, Todorović ZB, Nesic Z, Stojanović R, Divac N, Mikovic Z. Fentanyl Analogs: Structure-Activity-Relationship Study. in Current Medicinal Chemistry. 2009;16(19):2468-2474.
doi:10.2174/092986709788682074 .

Vuckovic, S., Prostran, M., Ivanović, Milovan, Došen-Mićović, Ljiljana, Todorović, Zoran B., Nesic, Z., Stojanović, R., Divac, N., Mikovic, Z., "Fentanyl Analogs: Structure-Activity-Relationship Study" in Current Medicinal Chemistry, 16, no. 19 (2009):2468-2474,
https://doi.org/10.2174/092986709788682074 . .