Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent
Апстракт
The computational method, based on molecular mechanics, with Monte Carlo type searching in dihedral angle space, was applied to the study of seven physiologically highly active fentanyl analogs, with different substituents in a phenethyl side chain. The low energy regions of the conformational space of these molecules have been compared in an effort to establish the receptor-recognized conformation of a phenethyl side chain, and to explain the mechanisms by which a hydroxyl substituent increases potency of the fentanyl analogs. It has been found that the extended conformation of a phenethyl side chain is the only one available to all the active analogs of fentanyl. Activities of the compounds with alkyl substituents in the phenethyl side chain correlate with their hydrophobicities, A hydroxyl substituent affects potency by reducing the flexibility of the phenethyl side chain, by reducing the energy difference between the global minimum and the receptor-recognized conformation and by sp...ecific interactions with the receptor.
Кључне речи:
fentanyl analogs / molecular mechanics / molecular modeling / structure-activity relationshipИзвор:
Electronic Journal of Theoretical Chemistry, 1996, 1, 199-210Издавач:
- John Wiley & Sons Ltd, W Sussex
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - DosenMicovic, L AU - Roglić, Goran AU - Mićović, Ivan V. AU - Ivanović, Milovan PY - 1996 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2583 AB - The computational method, based on molecular mechanics, with Monte Carlo type searching in dihedral angle space, was applied to the study of seven physiologically highly active fentanyl analogs, with different substituents in a phenethyl side chain. The low energy regions of the conformational space of these molecules have been compared in an effort to establish the receptor-recognized conformation of a phenethyl side chain, and to explain the mechanisms by which a hydroxyl substituent increases potency of the fentanyl analogs. It has been found that the extended conformation of a phenethyl side chain is the only one available to all the active analogs of fentanyl. Activities of the compounds with alkyl substituents in the phenethyl side chain correlate with their hydrophobicities, A hydroxyl substituent affects potency by reducing the flexibility of the phenethyl side chain, by reducing the energy difference between the global minimum and the receptor-recognized conformation and by specific interactions with the receptor. PB - John Wiley & Sons Ltd, W Sussex T2 - Electronic Journal of Theoretical Chemistry T1 - Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent VL - 1 SP - 199 EP - 210 UR - https://hdl.handle.net/21.15107/rcub_cherry_2583 ER -
@article{ author = "DosenMicovic, L and Roglić, Goran and Mićović, Ivan V. and Ivanović, Milovan", year = "1996", abstract = "The computational method, based on molecular mechanics, with Monte Carlo type searching in dihedral angle space, was applied to the study of seven physiologically highly active fentanyl analogs, with different substituents in a phenethyl side chain. The low energy regions of the conformational space of these molecules have been compared in an effort to establish the receptor-recognized conformation of a phenethyl side chain, and to explain the mechanisms by which a hydroxyl substituent increases potency of the fentanyl analogs. It has been found that the extended conformation of a phenethyl side chain is the only one available to all the active analogs of fentanyl. Activities of the compounds with alkyl substituents in the phenethyl side chain correlate with their hydrophobicities, A hydroxyl substituent affects potency by reducing the flexibility of the phenethyl side chain, by reducing the energy difference between the global minimum and the receptor-recognized conformation and by specific interactions with the receptor.", publisher = "John Wiley & Sons Ltd, W Sussex", journal = "Electronic Journal of Theoretical Chemistry", title = "Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent", volume = "1", pages = "199-210", url = "https://hdl.handle.net/21.15107/rcub_cherry_2583" }
DosenMicovic, L., Roglić, G., Mićović, I. V.,& Ivanović, M.. (1996). Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent. in Electronic Journal of Theoretical Chemistry John Wiley & Sons Ltd, W Sussex., 1, 199-210. https://hdl.handle.net/21.15107/rcub_cherry_2583
DosenMicovic L, Roglić G, Mićović IV, Ivanović M. Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent. in Electronic Journal of Theoretical Chemistry. 1996;1:199-210. https://hdl.handle.net/21.15107/rcub_cherry_2583 .
DosenMicovic, L, Roglić, Goran, Mićović, Ivan V., Ivanović, Milovan, "Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent" in Electronic Journal of Theoretical Chemistry, 1 (1996):199-210, https://hdl.handle.net/21.15107/rcub_cherry_2583 .