Synthesis and pharmacological evaluation of novel cis and trans 3-substituted anilidopiperidines
Samo za registrovane korisnike
2020
Autori
Jevtić, Ivana I.Savić-Vujović, Katarina
Srebro, Dragana
Vučković, Sonja M.
Ivanović, Milovan
Kostić-Rajačić, Slađana
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Background: 4-Anilidopiperidine class of synthetic opioid analgesics, with it’s representative fentanyl, are by far the most potent and clinically significant for the treatment of the severe chronic and surgical pain. However, side effects of μ-opioids are often quite serious. In order to improve the pharmacological profile of this class of opioid analgesics, a novel fentanyl analogs were designed, synthesized and evaluated in vivo for their antinociceptive activity. Methods: The title compounds were prepared using known synthetic transformations, including N-bromoacetamide mediated Hofmann rearrangement, highly selective carbamate cleavage with trimethylsilyl iodide and dehydration of carboxamide group to nitrile in the presence of SOCl2. The antinociceptive activity of the synthesized compounds was determined by tail-immersion and formalin test. Results: The scalable synthetic route towards novel fentanyl analogs bearing nitrogen groups in position C3 of piperidine ring is designed. ...In addition, Hofmann rearrangement was substantially improved for the more efficient synthesis of previously published 3-substituted fentanyl analogs. The series of ten fentanyl analogs was tested in vivo for their antinociceptive activity. The most potent compound of the series was found to be cis-4, based on the determined ED50 values in tail-immersion test. Conclusion: Of ten compounds tested for their antinociceptive activity, compound cis-4 is characterized by high potency, rapid beginning and short duration of action and due to this might be incorporated in different pharmaceutical forms.
Ključne reči:
Opioid / Fentanyl / Antinociceptive / AnilidopiperidineIzvor:
Pharmacological Reports, 2020, 72, 4, 1069-1075Izdavač:
- Springer
Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200026 (Univerzitet u Beogradu, Institut za hemiju, tehnologiju i metalurgiju - IHTM) (RS-MESTD-inst-2020-200026)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200110 (Univerzitet u Beogradu, Medicinski fakultet) (RS-MESTD-inst-2020-200110)
Napomena:
- Supplementary material: https://cherry.chem.bg.ac.rs/handle/123456789/4212
DOI: 10.1007/s43440-020-00121-2
ISSN: 1734-1140
WoS: 000547634000001
Scopus: 2-s2.0-85087288966
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Jevtić, Ivana I. AU - Savić-Vujović, Katarina AU - Srebro, Dragana AU - Vučković, Sonja M. AU - Ivanović, Milovan AU - Kostić-Rajačić, Slađana PY - 2020 UR - https://cherry.chem.bg.ac.rs/handle/123456789/4211 AB - Background: 4-Anilidopiperidine class of synthetic opioid analgesics, with it’s representative fentanyl, are by far the most potent and clinically significant for the treatment of the severe chronic and surgical pain. However, side effects of μ-opioids are often quite serious. In order to improve the pharmacological profile of this class of opioid analgesics, a novel fentanyl analogs were designed, synthesized and evaluated in vivo for their antinociceptive activity. Methods: The title compounds were prepared using known synthetic transformations, including N-bromoacetamide mediated Hofmann rearrangement, highly selective carbamate cleavage with trimethylsilyl iodide and dehydration of carboxamide group to nitrile in the presence of SOCl2. The antinociceptive activity of the synthesized compounds was determined by tail-immersion and formalin test. Results: The scalable synthetic route towards novel fentanyl analogs bearing nitrogen groups in position C3 of piperidine ring is designed. In addition, Hofmann rearrangement was substantially improved for the more efficient synthesis of previously published 3-substituted fentanyl analogs. The series of ten fentanyl analogs was tested in vivo for their antinociceptive activity. The most potent compound of the series was found to be cis-4, based on the determined ED50 values in tail-immersion test. Conclusion: Of ten compounds tested for their antinociceptive activity, compound cis-4 is characterized by high potency, rapid beginning and short duration of action and due to this might be incorporated in different pharmaceutical forms. PB - Springer T2 - Pharmacological Reports T1 - Synthesis and pharmacological evaluation of novel cis and trans 3-substituted anilidopiperidines VL - 72 IS - 4 SP - 1069 EP - 1075 DO - 10.1007/s43440-020-00121-2 ER -
@article{ author = "Jevtić, Ivana I. and Savić-Vujović, Katarina and Srebro, Dragana and Vučković, Sonja M. and Ivanović, Milovan and Kostić-Rajačić, Slađana", year = "2020", abstract = "Background: 4-Anilidopiperidine class of synthetic opioid analgesics, with it’s representative fentanyl, are by far the most potent and clinically significant for the treatment of the severe chronic and surgical pain. However, side effects of μ-opioids are often quite serious. In order to improve the pharmacological profile of this class of opioid analgesics, a novel fentanyl analogs were designed, synthesized and evaluated in vivo for their antinociceptive activity. Methods: The title compounds were prepared using known synthetic transformations, including N-bromoacetamide mediated Hofmann rearrangement, highly selective carbamate cleavage with trimethylsilyl iodide and dehydration of carboxamide group to nitrile in the presence of SOCl2. The antinociceptive activity of the synthesized compounds was determined by tail-immersion and formalin test. Results: The scalable synthetic route towards novel fentanyl analogs bearing nitrogen groups in position C3 of piperidine ring is designed. In addition, Hofmann rearrangement was substantially improved for the more efficient synthesis of previously published 3-substituted fentanyl analogs. The series of ten fentanyl analogs was tested in vivo for their antinociceptive activity. The most potent compound of the series was found to be cis-4, based on the determined ED50 values in tail-immersion test. Conclusion: Of ten compounds tested for their antinociceptive activity, compound cis-4 is characterized by high potency, rapid beginning and short duration of action and due to this might be incorporated in different pharmaceutical forms.", publisher = "Springer", journal = "Pharmacological Reports", title = "Synthesis and pharmacological evaluation of novel cis and trans 3-substituted anilidopiperidines", volume = "72", number = "4", pages = "1069-1075", doi = "10.1007/s43440-020-00121-2" }
Jevtić, I. I., Savić-Vujović, K., Srebro, D., Vučković, S. M., Ivanović, M.,& Kostić-Rajačić, S.. (2020). Synthesis and pharmacological evaluation of novel cis and trans 3-substituted anilidopiperidines. in Pharmacological Reports Springer., 72(4), 1069-1075. https://doi.org/10.1007/s43440-020-00121-2
Jevtić II, Savić-Vujović K, Srebro D, Vučković SM, Ivanović M, Kostić-Rajačić S. Synthesis and pharmacological evaluation of novel cis and trans 3-substituted anilidopiperidines. in Pharmacological Reports. 2020;72(4):1069-1075. doi:10.1007/s43440-020-00121-2 .
Jevtić, Ivana I., Savić-Vujović, Katarina, Srebro, Dragana, Vučković, Sonja M., Ivanović, Milovan, Kostić-Rajačić, Slađana, "Synthesis and pharmacological evaluation of novel cis and trans 3-substituted anilidopiperidines" in Pharmacological Reports, 72, no. 4 (2020):1069-1075, https://doi.org/10.1007/s43440-020-00121-2 . .