Fentanyl Analogs: Structure-Activity-Relationship Study
Nema prikaza
Autori
Vuckovic, S.Prostran, M.
Ivanović, Milovan
Došen-Mićović, Ljiljana
Todorović, Zoran B.
Nesic, Z.
Stojanović, R.
Divac, N.
Mikovic, Z.
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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 redu...ces 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.
Ključne reči:
Fentanyl / analogs / structure-activity-relationship (SAR) / analgesic activity / neurotoxicityIzvor:
Current Medicinal Chemistry, 2009, 16, 19, 2468-2474Izdavač:
- Bentham Science Publ Ltd, Sharjah
Finansiranje / projekti:
- Eksperimentalna i kliničko-farmakološka istraživanja mehanizma dejstva i interakcija lekova u nervnom i kardiovaskularnom sistemu (RS-MESTD-MPN2006-2010-145001)
DOI: 10.2174/092986709788682074
ISSN: 0929-8673
PubMed: 19601792
WoS: 000268258200008
Scopus: 2-s2.0-70349386048
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - 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 . .