3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis
Nema prikaza
Autori
Mićović, Ivan V.Ivanović, Milovan
Jovanovic-Micic, D
Beleslin, D.
Došen-Mićović, Ljiljana
Kiricojevic, VD
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
The synthesis of a novel analogue of fentanyl, 3-carbomethoxy fentanyl or "iso-carfentanil" has been accomplished in five steps, by simple and efficient route, starting from phenethyl amine and methyl acrylate. Both (+/-) lt (cis)under bar gt and -(+/-) lt (trans)under bar gt isomers were obtained in pure form and tested pharmacologically for the central analgesic activity: Preliminary results (rat-withdrawal test) revealed significant but substantially reduced potency of both isomers, the lt (trans)under bar gt in particular, compared to carfentanil. The computational (molecular mechanics) search of the conformational space low energy regions of lt (5a)under bar gt ((+/-) lt (cis)under bar gt ) and lt (5b)under bar gt ((+/-) lt (trans)under bar gt isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fe...ntanyl. This is believed to be the reason of its reduced potency relative to fentanyl.
Izvor:
Heterocyclic Communications, 1998, 4, 2, 171-179Izdavač:
- Walter De Gruyter Gmbh, Berlin
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Mićović, Ivan V. AU - Ivanović, Milovan AU - Jovanovic-Micic, D AU - Beleslin, D. AU - Došen-Mićović, Ljiljana AU - Kiricojevic, VD PY - 1998 UR - https://cherry.chem.bg.ac.rs/handle/123456789/381 AB - The synthesis of a novel analogue of fentanyl, 3-carbomethoxy fentanyl or "iso-carfentanil" has been accomplished in five steps, by simple and efficient route, starting from phenethyl amine and methyl acrylate. Both (+/-) lt (cis)under bar gt and -(+/-) lt (trans)under bar gt isomers were obtained in pure form and tested pharmacologically for the central analgesic activity: Preliminary results (rat-withdrawal test) revealed significant but substantially reduced potency of both isomers, the lt (trans)under bar gt in particular, compared to carfentanil. The computational (molecular mechanics) search of the conformational space low energy regions of lt (5a)under bar gt ((+/-) lt (cis)under bar gt ) and lt (5b)under bar gt ((+/-) lt (trans)under bar gt isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl. PB - Walter De Gruyter Gmbh, Berlin T2 - Heterocyclic Communications T1 - 3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis VL - 4 IS - 2 SP - 171 EP - 179 UR - https://hdl.handle.net/21.15107/rcub_cherry_381 ER -
@article{ author = "Mićović, Ivan V. and Ivanović, Milovan and Jovanovic-Micic, D and Beleslin, D. and Došen-Mićović, Ljiljana and Kiricojevic, VD", year = "1998", abstract = "The synthesis of a novel analogue of fentanyl, 3-carbomethoxy fentanyl or "iso-carfentanil" has been accomplished in five steps, by simple and efficient route, starting from phenethyl amine and methyl acrylate. Both (+/-) lt (cis)under bar gt and -(+/-) lt (trans)under bar gt isomers were obtained in pure form and tested pharmacologically for the central analgesic activity: Preliminary results (rat-withdrawal test) revealed significant but substantially reduced potency of both isomers, the lt (trans)under bar gt in particular, compared to carfentanil. The computational (molecular mechanics) search of the conformational space low energy regions of lt (5a)under bar gt ((+/-) lt (cis)under bar gt ) and lt (5b)under bar gt ((+/-) lt (trans)under bar gt isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl.", publisher = "Walter De Gruyter Gmbh, Berlin", journal = "Heterocyclic Communications", title = "3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis", volume = "4", number = "2", pages = "171-179", url = "https://hdl.handle.net/21.15107/rcub_cherry_381" }
Mićović, I. V., Ivanović, M., Jovanovic-Micic, D., Beleslin, D., Došen-Mićović, L.,& Kiricojevic, V.. (1998). 3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis. in Heterocyclic Communications Walter De Gruyter Gmbh, Berlin., 4(2), 171-179. https://hdl.handle.net/21.15107/rcub_cherry_381
Mićović IV, Ivanović M, Jovanovic-Micic D, Beleslin D, Došen-Mićović L, Kiricojevic V. 3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis. in Heterocyclic Communications. 1998;4(2):171-179. https://hdl.handle.net/21.15107/rcub_cherry_381 .
Mićović, Ivan V., Ivanović, Milovan, Jovanovic-Micic, D, Beleslin, D., Došen-Mićović, Ljiljana, Kiricojevic, VD, "3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis" in Heterocyclic Communications, 4, no. 2 (1998):171-179, https://hdl.handle.net/21.15107/rcub_cherry_381 .