TY  - JOUR
AU  - Jevtić, Ivana
AU  - Došen-Mićović, Ljiljana
AU  - Ivanović, Evica
AU  - Todorović, Nina
AU  - Ivanović, Milovan D.
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2142
AB  - The synthesis of orthogonally protected cis- and trans-3-amino-4-anilidopiperidine derivatives has been accomplished in six steps, starting from readily accessible 4-piperidone derivatives. The last three steps, i.e., N-acylation, Hofmann rearrangement, and carbamate cleavage, involved separated (+/-)-cis and (+/-)-trans intermediates. Complete retention of configuration was observed at position 3 of the piperidine ring. Specifically protected positions 1 and 3 at the piperidine scaffold allow for selective deprotection and introduction of diverse substituents at the respective nitrogen sites. The orthogonally protected anilidopiperidines open avenues to potentially pharmacologically active compounds, including opioids and various bivalent ligands for G protein-coupled receptors. In addition, a prototype of a novel class of fentanyl derivatives, possessing a 3-amino group, was synthesized by using the same approach.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Synthesis
T1  - Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl
VL  - 49
IS  - 14
SP  - 3126
EP  - 3136
DO  - 10.1055/s-0036-1588985
ER  - 

@article{
author = "Jevtić, Ivana and Došen-Mićović, Ljiljana and Ivanović, Evica and Todorović, Nina and Ivanović, Milovan D.",
year = "2017",
abstract = "The synthesis of orthogonally protected cis- and trans-3-amino-4-anilidopiperidine derivatives has been accomplished in six steps, starting from readily accessible 4-piperidone derivatives. The last three steps, i.e., N-acylation, Hofmann rearrangement, and carbamate cleavage, involved separated (+/-)-cis and (+/-)-trans intermediates. Complete retention of configuration was observed at position 3 of the piperidine ring. Specifically protected positions 1 and 3 at the piperidine scaffold allow for selective deprotection and introduction of diverse substituents at the respective nitrogen sites. The orthogonally protected anilidopiperidines open avenues to potentially pharmacologically active compounds, including opioids and various bivalent ligands for G protein-coupled receptors. In addition, a prototype of a novel class of fentanyl derivatives, possessing a 3-amino group, was synthesized by using the same approach.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Synthesis",
title = "Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl",
volume = "49",
number = "14",
pages = "3126-3136",
doi = "10.1055/s-0036-1588985"
}

Jevtić, I., Došen-Mićović, L., Ivanović, E., Todorović, N.,& Ivanović, M. D.. (2017). Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl. in Synthesis
Georg Thieme Verlag Kg, Stuttgart., 49(14), 3126-3136.
https://doi.org/10.1055/s-0036-1588985

Jevtić I, Došen-Mićović L, Ivanović E, Todorović N, Ivanović MD. Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl. in Synthesis. 2017;49(14):3126-3136.
doi:10.1055/s-0036-1588985 .

Jevtić, Ivana, Došen-Mićović, Ljiljana, Ivanović, Evica, Todorović, Nina, Ivanović, Milovan D., "Synthesis of Orthogonally Protected (+/-)-3-Amino-4-anilidopiperidines and (+/-)-3-N-Carbomethoxyfentanyl" in Synthesis, 49, no. 14 (2017):3126-3136,
https://doi.org/10.1055/s-0036-1588985 . .

TY  - JOUR
AU  - Senćanski, Milan
AU  - Došen-Mićović, Ljiljana
AU  - Šukalović, Vladimir
AU  - Kostić Rajačić, Slađana
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1617
AB  - Contacts between aromatic rings and sulfur-containing amino acids are frequent in proteins. However, little is known about the nature of their interactions particularly if substituents are present on aromatic ring. In this paper, DFT quantum chemical calculations were used to study substituted benzenes in complex with hydrogen sulfide (H2S), methanethiol (CH3SH), and (Methylsulfanyl)methane (CH3SCH3). It was found that SH(...)a interaction is more stabilizing than the S(...)a interaction in the case of benzene, but this is changed with increasing electronegativity of the substituent on benzene ring. Although the change of energy of SH...pi and S-...pi interaction follows the conventional model of substituent effect, where S-...pi interactions are maximized and SH...pi interactions are diminished with electron-withdrawing substituent on benzene as a result of changes in the aryl it-system, it was found that it is mainly a consequence of direct electrostatic interaction between substituent and the sulfur-containing molecule. We also investigated the model system of Cys(...)Trp interaction, adjacent to a cluster of aromatic amino acids, in proteins, using explicit membrane molecular dynamics simulations results of D-3 dopamine receptor crystal structure as starting point. It was found that fluorination in aromatic cluster enhances the Cys(...)Trp interaction. The effect is maximized when transferred through the rest of aromatic system suggesting possible explanation for frequent contacts between sulfur-containing and aromatic amino acids in proteins and their effects on protein folding and stabilization.
PB  - Springer/Plenum Publishers, New York
T2  - Structural Chemistry
T1  - Theoretical insight into sulfur aromatic interactions with extension to D-2 receptor activation mechanism
VL  - 26
IS  - 4
SP  - 1139
EP  - 1149
DO  - 10.1007/s11224-015-0574-z
ER  - 

@article{
author = "Senćanski, Milan and Došen-Mićović, Ljiljana and Šukalović, Vladimir and Kostić Rajačić, Slađana",
year = "2015",
abstract = "Contacts between aromatic rings and sulfur-containing amino acids are frequent in proteins. However, little is known about the nature of their interactions particularly if substituents are present on aromatic ring. In this paper, DFT quantum chemical calculations were used to study substituted benzenes in complex with hydrogen sulfide (H2S), methanethiol (CH3SH), and (Methylsulfanyl)methane (CH3SCH3). It was found that SH(...)a interaction is more stabilizing than the S(...)a interaction in the case of benzene, but this is changed with increasing electronegativity of the substituent on benzene ring. Although the change of energy of SH...pi and S-...pi interaction follows the conventional model of substituent effect, where S-...pi interactions are maximized and SH...pi interactions are diminished with electron-withdrawing substituent on benzene as a result of changes in the aryl it-system, it was found that it is mainly a consequence of direct electrostatic interaction between substituent and the sulfur-containing molecule. We also investigated the model system of Cys(...)Trp interaction, adjacent to a cluster of aromatic amino acids, in proteins, using explicit membrane molecular dynamics simulations results of D-3 dopamine receptor crystal structure as starting point. It was found that fluorination in aromatic cluster enhances the Cys(...)Trp interaction. The effect is maximized when transferred through the rest of aromatic system suggesting possible explanation for frequent contacts between sulfur-containing and aromatic amino acids in proteins and their effects on protein folding and stabilization.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Structural Chemistry",
title = "Theoretical insight into sulfur aromatic interactions with extension to D-2 receptor activation mechanism",
volume = "26",
number = "4",
pages = "1139-1149",
doi = "10.1007/s11224-015-0574-z"
}

Senćanski, M., Došen-Mićović, L., Šukalović, V.,& Kostić Rajačić, S.. (2015). Theoretical insight into sulfur aromatic interactions with extension to D-2 receptor activation mechanism. in Structural Chemistry
Springer/Plenum Publishers, New York., 26(4), 1139-1149.
https://doi.org/10.1007/s11224-015-0574-z

Senćanski M, Došen-Mićović L, Šukalović V, Kostić Rajačić S. Theoretical insight into sulfur aromatic interactions with extension to D-2 receptor activation mechanism. in Structural Chemistry. 2015;26(4):1139-1149.
doi:10.1007/s11224-015-0574-z .

Senćanski, Milan, Došen-Mićović, Ljiljana, Šukalović, Vladimir, Kostić Rajačić, Slađana, "Theoretical insight into sulfur aromatic interactions with extension to D-2 receptor activation mechanism" in Structural Chemistry, 26, no. 4 (2015):1139-1149,
https://doi.org/10.1007/s11224-015-0574-z . .

TY  - JOUR
AU  - Senćanski, Milan
AU  - Šukalović, Vladimir
AU  - Shakib, Kaveh
AU  - Šoškić, Vukić
AU  - Došen-Mićović, Ljiljana
AU  - Kostić Rajačić, Slađana
PY  - 2014
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1504
AB  - In this paper, we report the molecular modeling of the 5HT(2A) receptor and the molecular docking of arylpiperazine-like ligands. The focus of the research was on explaining the effects the ligand structure has on the binding properties of the 5HT(2A) receptor and on the key interactions between the ligands and the receptor-binding site. To see what the receptor-ligand interactions were, various substituents were introduced in one part of the ligand, keeping the rest unchanged. In this way, using a docking analysis on the proposed 5HT(2A) receptor model, we identified key receptor-ligand interactions and determined their properties. Those properties were correlated with experimentally determined binding affinities in order to determine the structure to activity relationship of the examined compounds.
PB  - Wiley-Blackwell, Hoboken
T2  - Chemical Biology & Drug Design
T1  - Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions
VL  - 83
IS  - 4
SP  - 462
EP  - 471
DO  - 10.1111/cbdd.12261
ER  - 

@article{
author = "Senćanski, Milan and Šukalović, Vladimir and Shakib, Kaveh and Šoškić, Vukić and Došen-Mićović, Ljiljana and Kostić Rajačić, Slađana",
year = "2014",
abstract = "In this paper, we report the molecular modeling of the 5HT(2A) receptor and the molecular docking of arylpiperazine-like ligands. The focus of the research was on explaining the effects the ligand structure has on the binding properties of the 5HT(2A) receptor and on the key interactions between the ligands and the receptor-binding site. To see what the receptor-ligand interactions were, various substituents were introduced in one part of the ligand, keeping the rest unchanged. In this way, using a docking analysis on the proposed 5HT(2A) receptor model, we identified key receptor-ligand interactions and determined their properties. Those properties were correlated with experimentally determined binding affinities in order to determine the structure to activity relationship of the examined compounds.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Chemical Biology & Drug Design",
title = "Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions",
volume = "83",
number = "4",
pages = "462-471",
doi = "10.1111/cbdd.12261"
}

Senćanski, M., Šukalović, V., Shakib, K., Šoškić, V., Došen-Mićović, L.,& Kostić Rajačić, S.. (2014). Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions. in Chemical Biology & Drug Design
Wiley-Blackwell, Hoboken., 83(4), 462-471.
https://doi.org/10.1111/cbdd.12261

Senćanski M, Šukalović V, Shakib K, Šoškić V, Došen-Mićović L, Kostić Rajačić S. Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions. in Chemical Biology & Drug Design. 2014;83(4):462-471.
doi:10.1111/cbdd.12261 .

Senćanski, Milan, Šukalović, Vladimir, Shakib, Kaveh, Šoškić, Vukić, Došen-Mićović, Ljiljana, Kostić Rajačić, Slađana, "Molecular Modeling of 5HT(2A) Receptor - Arylpiperazine Ligands Interactions" in Chemical Biology & Drug Design, 83, no. 4 (2014):462-471,
https://doi.org/10.1111/cbdd.12261 . .

TY  - JOUR
AU  - Senćanski, Milan V.
AU  - Šukalović, Vladimir
AU  - Došen-Mićović, Ljiljana
AU  - Šoškić, Vukić
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Kostić Rajačić, Slađana
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1057
AB  - Molecular modelling studies were undertaken in order to identify key interactions of selected ligands with alpha(1A) adrenergic receptor, responsible for their binding and presumably receptor activation. The previously made model of alpha(1A) adrenergic receptor was optimized by molecular dynamics and different arylpiperazine ligands were docked. The results show a high correlation to the experimentally determined binding affinities. Ligand orientations and its interactions with specific amino acid residues in the binding site explain trends in its structure-activity relationship. The key interactions for those trends are mainly aromatic, which are suggested by the calculation of their ESP surfaces.
PB  - Inst Materials Physics, Bucharest
T2  - Digest Journal of Nanomaterials and Biostructures
T1  - Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands
VL  - 7
IS  - 4
SP  - 1767
EP  - 1777
UR  - https://hdl.handle.net/21.15107/rcub_cherry_1567
ER  - 

@article{
author = "Senćanski, Milan V. and Šukalović, Vladimir and Došen-Mićović, Ljiljana and Šoškić, Vukić and Andrić, Deana and Roglić, Goran and Kostić Rajačić, Slađana",
year = "2012",
abstract = "Molecular modelling studies were undertaken in order to identify key interactions of selected ligands with alpha(1A) adrenergic receptor, responsible for their binding and presumably receptor activation. The previously made model of alpha(1A) adrenergic receptor was optimized by molecular dynamics and different arylpiperazine ligands were docked. The results show a high correlation to the experimentally determined binding affinities. Ligand orientations and its interactions with specific amino acid residues in the binding site explain trends in its structure-activity relationship. The key interactions for those trends are mainly aromatic, which are suggested by the calculation of their ESP surfaces.",
publisher = "Inst Materials Physics, Bucharest",
journal = "Digest Journal of Nanomaterials and Biostructures",
title = "Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands",
volume = "7",
number = "4",
pages = "1767-1777",
url = "https://hdl.handle.net/21.15107/rcub_cherry_1567"
}

Senćanski, M. V., Šukalović, V., Došen-Mićović, L., Šoškić, V., Andrić, D., Roglić, G.,& Kostić Rajačić, S.. (2012). Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands. in Digest Journal of Nanomaterials and Biostructures
Inst Materials Physics, Bucharest., 7(4), 1767-1777.
https://hdl.handle.net/21.15107/rcub_cherry_1567

Senćanski MV, Šukalović V, Došen-Mićović L, Šoškić V, Andrić D, Roglić G, Kostić Rajačić S. Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands. in Digest Journal of Nanomaterials and Biostructures. 2012;7(4):1767-1777.
https://hdl.handle.net/21.15107/rcub_cherry_1567 .

Senćanski, Milan V., Šukalović, Vladimir, Došen-Mićović, Ljiljana, Šoškić, Vukić, Andrić, Deana, Roglić, Goran, Kostić Rajačić, Slađana, "Modeling interactions of alpha(1a) adrenergic receptor and different arylpiperazine ligands" in Digest Journal of Nanomaterials and Biostructures, 7, no. 4 (2012):1767-1777,
https://hdl.handle.net/21.15107/rcub_cherry_1567 .

TY  - JOUR
AU  - Senćanski, Milan V.
AU  - Šukalović, Vladimir
AU  - Došen-Mićović, Ljiljana
AU  - Šoškić, Vukić
AU  - Andrić, Deana
AU  - Roglić, Goran
AU  - Kostić Rajačić, Slađana
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1146
AB  - Molecular modelling studies were undertaken in order to identify key interactions of selected ligands with α1A adrenergic receptor, responsible for their binding and presumably receptor activation. The previously made model of α1A adrenergic receptor was optimized by molecular dynamics and different arylpiperazine ligands were docked. The results show a high correlation to the experimentally determined binding affinities. Ligand orientations and its interactions with specific amino acid residues in the binding site explain trends in its structure-activity relationship. The key interactions for those trends are mainly aromatic, which are suggested by the calculation of their ESP surfaces.
PB  - Inst Materials Physics, Bucharest
T2  - Digest Journal of Nanomaterials and Biostructures
T1  - Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands
VL  - 7
IS  - 4
SP  - 1761
EP  - 1777
UR  - https://hdl.handle.net/21.15107/rcub_cherry_112
ER  - 

@article{
author = "Senćanski, Milan V. and Šukalović, Vladimir and Došen-Mićović, Ljiljana and Šoškić, Vukić and Andrić, Deana and Roglić, Goran and Kostić Rajačić, Slađana",
year = "2012",
abstract = "Molecular modelling studies were undertaken in order to identify key interactions of selected ligands with α1A adrenergic receptor, responsible for their binding and presumably receptor activation. The previously made model of α1A adrenergic receptor was optimized by molecular dynamics and different arylpiperazine ligands were docked. The results show a high correlation to the experimentally determined binding affinities. Ligand orientations and its interactions with specific amino acid residues in the binding site explain trends in its structure-activity relationship. The key interactions for those trends are mainly aromatic, which are suggested by the calculation of their ESP surfaces.",
publisher = "Inst Materials Physics, Bucharest",
journal = "Digest Journal of Nanomaterials and Biostructures",
title = "Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands",
volume = "7",
number = "4",
pages = "1761-1777",
url = "https://hdl.handle.net/21.15107/rcub_cherry_112"
}

Senćanski, M. V., Šukalović, V., Došen-Mićović, L., Šoškić, V., Andrić, D., Roglić, G.,& Kostić Rajačić, S.. (2012). Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands. in Digest Journal of Nanomaterials and Biostructures
Inst Materials Physics, Bucharest., 7(4), 1761-1777.
https://hdl.handle.net/21.15107/rcub_cherry_112

Senćanski MV, Šukalović V, Došen-Mićović L, Šoškić V, Andrić D, Roglić G, Kostić Rajačić S. Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands. in Digest Journal of Nanomaterials and Biostructures. 2012;7(4):1761-1777.
https://hdl.handle.net/21.15107/rcub_cherry_112 .

Senćanski, Milan V., Šukalović, Vladimir, Došen-Mićović, Ljiljana, Šoškić, Vukić, Andrić, Deana, Roglić, Goran, Kostić Rajačić, Slađana, "Modeling interactions of α1a adrenergic receptor and different arylpiperazine ligands" in Digest Journal of Nanomaterials and Biostructures, 7, no. 4 (2012):1761-1777,
https://hdl.handle.net/21.15107/rcub_cherry_112 .

TY  - JOUR
AU  - Ivanović, Milovan D.
AU  - Mićović, Ivan
AU  - Vučković, Sonja
AU  - Prostran, Milica
AU  - Todorović, Zoran
AU  - Ivanović, Evica
AU  - Kiricojević, Vesna
AU  - Đorđević, Jelena B.
AU  - Došen-Mićović, Ljiljana
PY  - 2004
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2684
AB  - An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.1-5.5 (all new compounds) were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting beta-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methyl phenethylamine, (93% yield), was successively reacted with NaH and BuLi, to form the highly reactive alpha,gamma-dienolate anion 1.1a. Regio and chemoselective gamma-alkylation of the dienolate with various primary and secondary alkyl halides furnished the beta-keto-amides 1.2-1.5 (76-91%). Reductive amination of the keto-amides 1.1-1.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.1-2.5. afforded the beta-anilino amides 3.1-3.5 (74-85%). After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.1-4.5 were obtained (87-97%). The synthesis of (+/-)-2,3-seco-fentanyls 5.1-5.5 was completed by N-acylation of the diamines 4.1-4.5 with propionyl chloride, followed by precipitation of the monooxalate salts (86-95%). The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 5-6 times more active than morphine in rats. while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance. the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers.
AB  - Razvijen je efikasan postupak za dobijanje različitih acikličnih 1,3-diamina u pet faza, i primenjen u sintezi nove klase analoga fentanila otvorenog niza. Derivati 5.1–5.5 (svi su nova jedinjenja) sintetisani su sa ciljem da se proceni uticaj piperidinskog prstena na opioidnoanalgetičku aktivnost anilido-piperidina. Polazni β-keto-amid 1.1, dobijen aminolizom metilacetoacetata metilfenetilaminom (prinos 93 %), bio je sukcesivno tretiran sa NaH i BuLi, pri čemu je postao veoma reaktivni α,γ-dienolatni anjon 1.1a. Regio- i hemoselektivnim γ-alkilovanjem ovog dienolata različitim primarnim i sekundarnim alkil-halogenidima, dobijeni su β-keto-amidi 1.2–1.5 (prinos 76–91 %). Reduktivnim aminovanjem keto-amida 1.1–1.5 pomoću Zn praha i sirćetne kiseline, preko enaminskih intermedijera 2.1–2.5, postali su -anilino-amidi 3.1–3.5 (prinos 74–85 %). Posle reduktivne deoksigenacije tercijene amidne funkcije, koristeći in situ generisani diboran, odgovarajući 1,3-diamini 4.1–4.5 izolovani su u prinosima 87–97 %. Sinteza (±)-2,3-seco-fentanila 5.1–5.5 završena je N-acilovanjem diamina 4.1–4.5 propionil-hloridom, a zatim taloženjem u obliku monooksalatnih soli (prinos 86–95 %). Nađeno je da je osnovno jedinjenje, 2,3-seco fentanil 5.1, 40 puta slabiji narkotički analgetik od fentanila, ali još uvek 5–6 puta aktivniji od morfina u pacova, dok je i-Pr derivat 5.3 bio neaktivan. Osim farmakološkog značaja, opštim postupkom prikazanim u ovom radu, mogu se sintetisati različiti 1,3-diamini, uključujući i one sa funkcionalnim grupama. Ova jedinjenja mogu biti potencijalno značajna kao kompleksirajući agensi i kao intermedijeri u sintezi aza-kraun-etara.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - The synthesis and pharmacological evaluation of (+/-)-2,3-seco-fentanyl analogues
T1  - Sinteza i farmakološko ispitivanje (±)-2,3-seco-analoga fentanila
VL  - 69
IS  - 11
SP  - 955
EP  - 968
DO  - 10.2298/JSC0411955I
ER  - 

@article{
author = "Ivanović, Milovan D. and Mićović, Ivan and Vučković, Sonja and Prostran, Milica and Todorović, Zoran and Ivanović, Evica and Kiricojević, Vesna and Đorđević, Jelena B. and Došen-Mićović, Ljiljana",
year = "2004",
abstract = "An efficient, five-step synthetic approach to various acyclic 1,3-diamines has been developed and applied to the preparation of a novel class of open-chained fentanyl analogues. The acyclic derivatives 5.1-5.5 (all new compounds) were synthesized with the aim of estimating the significance of the piperidine ring for the opioid analgesic activity of anilido-piperidines. The starting beta-keto-amide 1.1, prepared by the aminolysis of methyl acetoacetate with methyl phenethylamine, (93% yield), was successively reacted with NaH and BuLi, to form the highly reactive alpha,gamma-dienolate anion 1.1a. Regio and chemoselective gamma-alkylation of the dienolate with various primary and secondary alkyl halides furnished the beta-keto-amides 1.2-1.5 (76-91%). Reductive amination of the keto-amides 1.1-1.5 with aniline and Zn powder in acetic acid, via the enamine intermediates 2.1-2.5. afforded the beta-anilino amides 3.1-3.5 (74-85%). After reductive deoxygenation of the tertiary amide group, using in situ generated diborane, the corresponding 1,3-diamines 4.1-4.5 were obtained (87-97%). The synthesis of (+/-)-2,3-seco-fentanyls 5.1-5.5 was completed by N-acylation of the diamines 4.1-4.5 with propionyl chloride, followed by precipitation of the monooxalate salts (86-95%). The parent compound, 2,3-seco-fentanyl 5.1, was found to be a 40 times less potent narcotic analgesic than fentanyl but still 5-6 times more active than morphine in rats. while i-Pr derivative 5.3 was inactive. Apart from the pharmacological significance. the general procedure described herein may afford various functionalized, 1,3-diamines as potential complexing agents and building blocks for the synthesis of aza-crown ethers., Razvijen je efikasan postupak za dobijanje različitih acikličnih 1,3-diamina u pet faza, i primenjen u sintezi nove klase analoga fentanila otvorenog niza. Derivati 5.1–5.5 (svi su nova jedinjenja) sintetisani su sa ciljem da se proceni uticaj piperidinskog prstena na opioidnoanalgetičku aktivnost anilido-piperidina. Polazni β-keto-amid 1.1, dobijen aminolizom metilacetoacetata metilfenetilaminom (prinos 93 %), bio je sukcesivno tretiran sa NaH i BuLi, pri čemu je postao veoma reaktivni α,γ-dienolatni anjon 1.1a. Regio- i hemoselektivnim γ-alkilovanjem ovog dienolata različitim primarnim i sekundarnim alkil-halogenidima, dobijeni su β-keto-amidi 1.2–1.5 (prinos 76–91 %). Reduktivnim aminovanjem keto-amida 1.1–1.5 pomoću Zn praha i sirćetne kiseline, preko enaminskih intermedijera 2.1–2.5, postali su -anilino-amidi 3.1–3.5 (prinos 74–85 %). Posle reduktivne deoksigenacije tercijene amidne funkcije, koristeći in situ generisani diboran, odgovarajući 1,3-diamini 4.1–4.5 izolovani su u prinosima 87–97 %. Sinteza (±)-2,3-seco-fentanila 5.1–5.5 završena je N-acilovanjem diamina 4.1–4.5 propionil-hloridom, a zatim taloženjem u obliku monooksalatnih soli (prinos 86–95 %). Nađeno je da je osnovno jedinjenje, 2,3-seco fentanil 5.1, 40 puta slabiji narkotički analgetik od fentanila, ali još uvek 5–6 puta aktivniji od morfina u pacova, dok je i-Pr derivat 5.3 bio neaktivan. Osim farmakološkog značaja, opštim postupkom prikazanim u ovom radu, mogu se sintetisati različiti 1,3-diamini, uključujući i one sa funkcionalnim grupama. Ova jedinjenja mogu biti potencijalno značajna kao kompleksirajući agensi i kao intermedijeri u sintezi aza-kraun-etara.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "The synthesis and pharmacological evaluation of (+/-)-2,3-seco-fentanyl analogues, Sinteza i farmakološko ispitivanje (±)-2,3-seco-analoga fentanila",
volume = "69",
number = "11",
pages = "955-968",
doi = "10.2298/JSC0411955I"
}

Ivanović, M. D., Mićović, I., Vučković, S., Prostran, M., Todorović, Z., Ivanović, E., Kiricojević, V., Đorđević, J. B.,& Došen-Mićović, L.. (2004). The synthesis and pharmacological evaluation of (+/-)-2,3-seco-fentanyl analogues. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 69(11), 955-968.
https://doi.org/10.2298/JSC0411955I

Ivanović MD, Mićović I, Vučković S, Prostran M, Todorović Z, Ivanović E, Kiricojević V, Đorđević JB, Došen-Mićović L. The synthesis and pharmacological evaluation of (+/-)-2,3-seco-fentanyl analogues. in Journal of the Serbian Chemical Society. 2004;69(11):955-968.
doi:10.2298/JSC0411955I .

Ivanović, Milovan D., Mićović, Ivan, Vučković, Sonja, Prostran, Milica, Todorović, Zoran, Ivanović, Evica, Kiricojević, Vesna, Đorđević, Jelena B., Došen-Mićović, Ljiljana, "The synthesis and pharmacological evaluation of (+/-)-2,3-seco-fentanyl analogues" in Journal of the Serbian Chemical Society, 69, no. 11 (2004):955-968,
https://doi.org/10.2298/JSC0411955I . .

TY  - JOUR
AU  - Ivanović, Milovan D.
AU  - Mićović, Ivan
AU  - Vučković, Sonja
AU  - Prostran, Milica
AU  - Todorović, Zoran
AU  - Kiricojević, Vesna
AU  - Đorđević, Jelena B.
AU  - Došen-Mićović, Ljiljana
PY  - 2004
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2685
AB  - A general five step method for the synthesis of 3-alkylfentanyl analogues (i.e. cis and trans 3-alkyl-4-anilidopiperidines 6.1-6.6) has been developed, The starting N-phenethyl-4-piperidone 1 was first converted into the cyclohexylimine derivative 2. alpha-deprotonated with butyllithium and die resulting imine anion efficiently monoalkylated with primary, and secondary alkyl halides. After mild acid hydrolysis. the obtained 3-alkyl-4-piperidones 3.1-3.6 were isolated in good yields (79-85%), then condensed with aniline to form imines 4.1-4.6. Subsequent reduction of the imines (LiAlH4/THF) yielded cis/trans mixtures of 3-alkyl-4-anilinopiperidines 5.1-5.6. Quantitative separation of the diastereoisomers by column chromatography of Al2O3 gave pure cis 5.1-5.6 (29-51% yield) and trans 5.1-5.6 (19-27% yield), with the cis/trans ratio in the range 7/3-6/4 . The synthesis was concluded by N-acylation of the purified 5.1-5.6, with propionyl chloride, to afford cis and trans 3-alkyl-4-anilidopiperidines 6.1-6.6 (approximate to 95% yield, as monooxalate salts). No enatioseparation was attempted at any stage. The relative cis/trans stereochemistry was provisionally assigned from the H-1-NMR spectra. Of the twelve synthesized 3-alkylfentanyls. ten compounds (two known and eight novel derivatives, all as the monooxalate salts) were preliminarily tested as analgesics in rats, comparing the potency to fentanyl. Except for the known (+/-)-cis-3-Me fentanyl 6.1cis. (8 x fentanyl), and the novel (+/-)-cis-3-Et fentanyl 6.2cis. (1.5 x fentanyl), all of the others were less active than fentanyl or inactive. Some tentative conclusions on the structure-activity relationship (SAR) in this series of derivatives have been made.
AB  - Razvijen je opšti metod za sintezu 3-alkil analoga fentanila (tj. cis i trans 3-alkil-4-anilidopiperidina 6.1–6.6) u pet faza. Polazni N-fenetil-4-piperidon 1 prvo je preveden u cikloheksiliminski derivat 2, α-deprotonovan butillitijumom, a postali iminski anjon efikasno monoalkilovan primarnim i sekundarnim alkilhalogenidima. Posle blage kisele hidrolize, nastali 3-alkil-4-piperidoni 3.1–3.6 izolovani su u dobrim prinosima (79–85 %), zatim kondenzovani sa anilinom do imina 4.1–4.6. Redukcijom ovih imina (LiAlH4/THF) dobijene su cis/trans smese 3-alkil-4-anilinopiperidina 5.1–5.6. Kvantitativnim hromatografskim razdvajanjem dijastereoizomera na stubu Al2O3 izolovani su čisti cis 5.1–5.6 (prinos 29–51 %) i trans 5.1–5.6 (prinos 19–27 %), gde je cis/trans odnos bio u opsegu 7/3–6/4. Sinteza je završena N-acilovanjem prečišćenih intermedijera 5.1–5.6 pomoću propionil-hlorida, pri čemu su postali cis i trans 3-alkil-4-anilidopiperidini 6.1–6.6 (prinos _ 95 %, kao monooksalatne soli). Ni u jednoj fazi nije pokušano razdvajanje enantiomera. Relativna, cis/trans, stereohemija preliminarno je određena iz 1H-NMRspektra. Od dvanaest sintetisanih 3-alkil-fentanila, deset jedinjenja (dva poznata i osam novih, sva u obliku monookasalatnih soli) preliminarno su testirana kao analgetici na pacovima, poredeći aktivnost sa fentanilom.Osim poznatog (±)-cis-3-Me fentanila 6.1 cis, (8 x fentanil), i novog (±)-cis-3-Et fentanila 6.2 cis, (1,5 x fentanil), svi ostali bili su manje aktivni ili neaktivni. Izvedeni su određeni, preliminarni zaključci u vezi odnosa strukture i aktivnosti u ovoj seriji derivata.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - The synthesis and preliminary pharmacological evaluation of the racemic cis and trans 3-alkylfentanyl analogues
T1  - Sinteza i preliminarni farmakološki testovi recemskih cis i trans 3-alkilanaloga fentanila
VL  - 69
IS  - 7
SP  - 511
EP  - 526
DO  - 10.2298/JSC0407511I
ER  - 

@article{
author = "Ivanović, Milovan D. and Mićović, Ivan and Vučković, Sonja and Prostran, Milica and Todorović, Zoran and Kiricojević, Vesna and Đorđević, Jelena B. and Došen-Mićović, Ljiljana",
year = "2004",
abstract = "A general five step method for the synthesis of 3-alkylfentanyl analogues (i.e. cis and trans 3-alkyl-4-anilidopiperidines 6.1-6.6) has been developed, The starting N-phenethyl-4-piperidone 1 was first converted into the cyclohexylimine derivative 2. alpha-deprotonated with butyllithium and die resulting imine anion efficiently monoalkylated with primary, and secondary alkyl halides. After mild acid hydrolysis. the obtained 3-alkyl-4-piperidones 3.1-3.6 were isolated in good yields (79-85%), then condensed with aniline to form imines 4.1-4.6. Subsequent reduction of the imines (LiAlH4/THF) yielded cis/trans mixtures of 3-alkyl-4-anilinopiperidines 5.1-5.6. Quantitative separation of the diastereoisomers by column chromatography of Al2O3 gave pure cis 5.1-5.6 (29-51% yield) and trans 5.1-5.6 (19-27% yield), with the cis/trans ratio in the range 7/3-6/4 . The synthesis was concluded by N-acylation of the purified 5.1-5.6, with propionyl chloride, to afford cis and trans 3-alkyl-4-anilidopiperidines 6.1-6.6 (approximate to 95% yield, as monooxalate salts). No enatioseparation was attempted at any stage. The relative cis/trans stereochemistry was provisionally assigned from the H-1-NMR spectra. Of the twelve synthesized 3-alkylfentanyls. ten compounds (two known and eight novel derivatives, all as the monooxalate salts) were preliminarily tested as analgesics in rats, comparing the potency to fentanyl. Except for the known (+/-)-cis-3-Me fentanyl 6.1cis. (8 x fentanyl), and the novel (+/-)-cis-3-Et fentanyl 6.2cis. (1.5 x fentanyl), all of the others were less active than fentanyl or inactive. Some tentative conclusions on the structure-activity relationship (SAR) in this series of derivatives have been made., Razvijen je opšti metod za sintezu 3-alkil analoga fentanila (tj. cis i trans 3-alkil-4-anilidopiperidina 6.1–6.6) u pet faza. Polazni N-fenetil-4-piperidon 1 prvo je preveden u cikloheksiliminski derivat 2, α-deprotonovan butillitijumom, a postali iminski anjon efikasno monoalkilovan primarnim i sekundarnim alkilhalogenidima. Posle blage kisele hidrolize, nastali 3-alkil-4-piperidoni 3.1–3.6 izolovani su u dobrim prinosima (79–85 %), zatim kondenzovani sa anilinom do imina 4.1–4.6. Redukcijom ovih imina (LiAlH4/THF) dobijene su cis/trans smese 3-alkil-4-anilinopiperidina 5.1–5.6. Kvantitativnim hromatografskim razdvajanjem dijastereoizomera na stubu Al2O3 izolovani su čisti cis 5.1–5.6 (prinos 29–51 %) i trans 5.1–5.6 (prinos 19–27 %), gde je cis/trans odnos bio u opsegu 7/3–6/4. Sinteza je završena N-acilovanjem prečišćenih intermedijera 5.1–5.6 pomoću propionil-hlorida, pri čemu su postali cis i trans 3-alkil-4-anilidopiperidini 6.1–6.6 (prinos _ 95 %, kao monooksalatne soli). Ni u jednoj fazi nije pokušano razdvajanje enantiomera. Relativna, cis/trans, stereohemija preliminarno je određena iz 1H-NMRspektra. Od dvanaest sintetisanih 3-alkil-fentanila, deset jedinjenja (dva poznata i osam novih, sva u obliku monookasalatnih soli) preliminarno su testirana kao analgetici na pacovima, poredeći aktivnost sa fentanilom.Osim poznatog (±)-cis-3-Me fentanila 6.1 cis, (8 x fentanil), i novog (±)-cis-3-Et fentanila 6.2 cis, (1,5 x fentanil), svi ostali bili su manje aktivni ili neaktivni. Izvedeni su određeni, preliminarni zaključci u vezi odnosa strukture i aktivnosti u ovoj seriji derivata.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "The synthesis and preliminary pharmacological evaluation of the racemic cis and trans 3-alkylfentanyl analogues, Sinteza i preliminarni farmakološki testovi recemskih cis i trans 3-alkilanaloga fentanila",
volume = "69",
number = "7",
pages = "511-526",
doi = "10.2298/JSC0407511I"
}

Ivanović, M. D., Mićović, I., Vučković, S., Prostran, M., Todorović, Z., Kiricojević, V., Đorđević, J. B.,& Došen-Mićović, L.. (2004). The synthesis and preliminary pharmacological evaluation of the racemic cis and trans 3-alkylfentanyl analogues. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 69(7), 511-526.
https://doi.org/10.2298/JSC0407511I

Ivanović MD, Mićović I, Vučković S, Prostran M, Todorović Z, Kiricojević V, Đorđević JB, Došen-Mićović L. The synthesis and preliminary pharmacological evaluation of the racemic cis and trans 3-alkylfentanyl analogues. in Journal of the Serbian Chemical Society. 2004;69(7):511-526.
doi:10.2298/JSC0407511I .

Ivanović, Milovan D., Mićović, Ivan, Vučković, Sonja, Prostran, Milica, Todorović, Zoran, Kiricojević, Vesna, Đorđević, Jelena B., Došen-Mićović, Ljiljana, "The synthesis and preliminary pharmacological evaluation of the racemic cis and trans 3-alkylfentanyl analogues" in Journal of the Serbian Chemical Society, 69, no. 7 (2004):511-526,
https://doi.org/10.2298/JSC0407511I . .

TY  - JOUR
AU  - Kiricojević, Vesna
AU  - Ivanović, Milovan D.
AU  - Mićović, Ivan
AU  - Đorđević, Jelena B.
AU  - Roglić, Goran
AU  - Došen-Mićović, Ljiljana
PY  - 2002
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2677
AB  - An efficient synthesis of methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate (7) has been developed, starting from 1-benzylpiperidin-4-one (1), The compound is a key intermediate in the synthesis of new generation, highly active narcotic analgesics, such as remifentanil. as well as the novel classes of fentanyl analogues, An optimized Strecker-type condensation of piperidone 1 with aniline and HCN yielded the anilino-nitrile 2 (approximate to90%) which, upon selective hydrolysis with cone. H2SO4, gave the anilino-amide 3. After vigorous basic hydrolysis of 3, followed by acidification and successive treatment with SOCl2 and MeOH, the anilino-ester 5 was obtained (40-45%, in 3 steps). N-Acylation of 5 with propionyl chloride yielded the anilido-ester 6 (70-80%). In the final step, the catalytic N-debenzylation of 6 was examined under various conditions and optimized to yield 7 in near quantitative yields.
AB  - U ovom radu razvijena je efikasna sinteza metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata (7), prolazeći od 1-benzil piperidin-4-on-1 (1). Jedinjenje 7 je ključni intermedijer u sintezi nove generacije visoko aktivnih narkotičkih analgetika, kao što je remifentanil a takođe i novih klasa analoga fentanyla. U optimizovanoj Strecker-ovoj kondenzaciji priperidona 1 sa anilinom i HCN, dobijen je anilino-nitril 2 (≈90%) prinos čijom je selektivnom hidrolizom pomoću konc. H2SO4 postao anilino-amid 3. Intenzivnom baznom hidrolizom ovog intermedijera, zakišeljavanjem a zatim sukcesivno reakcijom sa SOCl2 i MeOH sintetisan je anilino-estar 5 (≈40–45% prinos u 3 faze). N-acelovanjem anilino-estra 5 sa propionil hloridom postao je anilido-estar 6 (≈70–80% prinos). U poslednjom fazi sinteze izvršena je optimizacija katalitičkog N-debenzilovanja anilido-estra 6 do finalnog proizvoda 7, u približno kvantitativnom prinosu.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate
T1  - Optimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata
VL  - 67
IS  - 12
SP  - 793
EP  - 802
DO  - 10.2298/JSC0212793K
ER  - 

@article{
author = "Kiricojević, Vesna and Ivanović, Milovan D. and Mićović, Ivan and Đorđević, Jelena B. and Roglić, Goran and Došen-Mićović, Ljiljana",
year = "2002",
abstract = "An efficient synthesis of methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate (7) has been developed, starting from 1-benzylpiperidin-4-one (1), The compound is a key intermediate in the synthesis of new generation, highly active narcotic analgesics, such as remifentanil. as well as the novel classes of fentanyl analogues, An optimized Strecker-type condensation of piperidone 1 with aniline and HCN yielded the anilino-nitrile 2 (approximate to90%) which, upon selective hydrolysis with cone. H2SO4, gave the anilino-amide 3. After vigorous basic hydrolysis of 3, followed by acidification and successive treatment with SOCl2 and MeOH, the anilino-ester 5 was obtained (40-45%, in 3 steps). N-Acylation of 5 with propionyl chloride yielded the anilido-ester 6 (70-80%). In the final step, the catalytic N-debenzylation of 6 was examined under various conditions and optimized to yield 7 in near quantitative yields., U ovom radu razvijena je efikasna sinteza metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata (7), prolazeći od 1-benzil piperidin-4-on-1 (1). Jedinjenje 7 je ključni intermedijer u sintezi nove generacije visoko aktivnih narkotičkih analgetika, kao što je remifentanil a takođe i novih klasa analoga fentanyla. U optimizovanoj Strecker-ovoj kondenzaciji priperidona 1 sa anilinom i HCN, dobijen je anilino-nitril 2 (≈90%) prinos čijom je selektivnom hidrolizom pomoću konc. H2SO4 postao anilino-amid 3. Intenzivnom baznom hidrolizom ovog intermedijera, zakišeljavanjem a zatim sukcesivno reakcijom sa SOCl2 i MeOH sintetisan je anilino-estar 5 (≈40–45% prinos u 3 faze). N-acelovanjem anilino-estra 5 sa propionil hloridom postao je anilido-estar 6 (≈70–80% prinos). U poslednjom fazi sinteze izvršena je optimizacija katalitičkog N-debenzilovanja anilido-estra 6 do finalnog proizvoda 7, u približno kvantitativnom prinosu.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate, Optimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata",
volume = "67",
number = "12",
pages = "793-802",
doi = "10.2298/JSC0212793K"
}

Kiricojević, V., Ivanović, M. D., Mićović, I., Đorđević, J. B., Roglić, G.,& Došen-Mićović, L.. (2002). An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 67(12), 793-802.
https://doi.org/10.2298/JSC0212793K

Kiricojević V, Ivanović MD, Mićović I, Đorđević JB, Roglić G, Došen-Mićović L. An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate. in Journal of the Serbian Chemical Society. 2002;67(12):793-802.
doi:10.2298/JSC0212793K .

Kiricojević, Vesna, Ivanović, Milovan D., Mićović, Ivan, Đorđević, Jelena B., Roglić, Goran, Došen-Mićović, Ljiljana, "An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate" in Journal of the Serbian Chemical Society, 67, no. 12 (2002):793-802,
https://doi.org/10.2298/JSC0212793K . .

TY  - JOUR
AU  - Došen-Mićović, Ljiljana
AU  - Jeremić, D.
PY  - 1985
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4519
AB  - The conformational equilibrium has been measured for r-1,c-3-dichloro-t-5-methylcyclohexane(2) in six solvents from the 500 MHz and 400 MHz 1H NMR spectra. The room-temperature and low-temperature C1H couplings are used as well as the vicinal proton-proton coupling constants based on the MM2-calculated dihedral angles and the empirically generalized Karplus equation. The equilibrium exhibits a very weak solvent dependence; ΔGaa-ee varies from 1.22 kcal mol-1 in CDCl3 to 0.87 kcal mol-1 in DMSO-d6. The free energy difference, Δaa-ee II 0.90 kcal mol-1, in CD2Cl2 is determined by peak-area NMR measurements at -100°C. The reaction field theory is used to calculate the variation of Δaa-ee with solvent polarity. The calculated solvent shift δΔGaa-ee (CDCl3 to DMSO-d6) is -0.21 kcal mol-1, compared with -0.35 kcal mol-1 determined experimentally.
PB  - Elsevier
T2  - Journal of Molecular Structure
T1  - The solvent effect on the conformational equilibrium of 1,3-dichloro-5-methylcylclohexane
VL  - 131
IS  - 3-4
SP  - 261
EP  - 266
DO  - 10.1016/0022-2860(85)87027-7
ER  - 

@article{
author = "Došen-Mićović, Ljiljana and Jeremić, D.",
year = "1985",
abstract = "The conformational equilibrium has been measured for r-1,c-3-dichloro-t-5-methylcyclohexane(2) in six solvents from the 500 MHz and 400 MHz 1H NMR spectra. The room-temperature and low-temperature C1H couplings are used as well as the vicinal proton-proton coupling constants based on the MM2-calculated dihedral angles and the empirically generalized Karplus equation. The equilibrium exhibits a very weak solvent dependence; ΔGaa-ee varies from 1.22 kcal mol-1 in CDCl3 to 0.87 kcal mol-1 in DMSO-d6. The free energy difference, Δaa-ee II 0.90 kcal mol-1, in CD2Cl2 is determined by peak-area NMR measurements at -100°C. The reaction field theory is used to calculate the variation of Δaa-ee with solvent polarity. The calculated solvent shift δΔGaa-ee (CDCl3 to DMSO-d6) is -0.21 kcal mol-1, compared with -0.35 kcal mol-1 determined experimentally.",
publisher = "Elsevier",
journal = "Journal of Molecular Structure",
title = "The solvent effect on the conformational equilibrium of 1,3-dichloro-5-methylcylclohexane",
volume = "131",
number = "3-4",
pages = "261-266",
doi = "10.1016/0022-2860(85)87027-7"
}

Došen-Mićović, L.,& Jeremić, D.. (1985). The solvent effect on the conformational equilibrium of 1,3-dichloro-5-methylcylclohexane. in Journal of Molecular Structure
Elsevier., 131(3-4), 261-266.
https://doi.org/10.1016/0022-2860(85)87027-7

Došen-Mićović L, Jeremić D. The solvent effect on the conformational equilibrium of 1,3-dichloro-5-methylcylclohexane. in Journal of Molecular Structure. 1985;131(3-4):261-266.
doi:10.1016/0022-2860(85)87027-7 .

Došen-Mićović, Ljiljana, Jeremić, D., "The solvent effect on the conformational equilibrium of 1,3-dichloro-5-methylcylclohexane" in Journal of Molecular Structure, 131, no. 3-4 (1985):261-266,
https://doi.org/10.1016/0022-2860(85)87027-7 . .

TY  - JOUR
AU  - Došen-Mićović, Ljiljana
AU  - Žigman, Vida I.
PY  - 1985
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4502
AB  - The reaction-field theory based on dipole and quadrupole interactions has been generalized, yielding an expression for the energy as a function of point dipole and quadrupole position and orientation within a spherical cavity in a dielectric medium. The effect of displacement of molecular dipole and quadrupole, from the centre of the solute cavity, on the conformational free energy in solution has been investigated for some halogenocyclohexanes, cyclohexanones, and ethers.
PB  - Royal Society of Chemistry
T2  - Journal of the Chemical Society, Perkin Transactions 2
T1  - Solvent effect on conformational equilibria. Solvation energy as a function of solute position and orientation within a cavity in a dielectric medium
IS  - 5
SP  - 625
EP  - 631
DO  - 10.1039/P29850000625
ER  - 

@article{
author = "Došen-Mićović, Ljiljana and Žigman, Vida I.",
year = "1985",
abstract = "The reaction-field theory based on dipole and quadrupole interactions has been generalized, yielding an expression for the energy as a function of point dipole and quadrupole position and orientation within a spherical cavity in a dielectric medium. The effect of displacement of molecular dipole and quadrupole, from the centre of the solute cavity, on the conformational free energy in solution has been investigated for some halogenocyclohexanes, cyclohexanones, and ethers.",
publisher = "Royal Society of Chemistry",
journal = "Journal of the Chemical Society, Perkin Transactions 2",
title = "Solvent effect on conformational equilibria. Solvation energy as a function of solute position and orientation within a cavity in a dielectric medium",
number = "5",
pages = "625-631",
doi = "10.1039/P29850000625"
}

Došen-Mićović, L.,& Žigman, V. I.. (1985). Solvent effect on conformational equilibria. Solvation energy as a function of solute position and orientation within a cavity in a dielectric medium. in Journal of the Chemical Society, Perkin Transactions 2
Royal Society of Chemistry.(5), 625-631.
https://doi.org/10.1039/P29850000625

Došen-Mićović L, Žigman VI. Solvent effect on conformational equilibria. Solvation energy as a function of solute position and orientation within a cavity in a dielectric medium. in Journal of the Chemical Society, Perkin Transactions 2. 1985;(5):625-631.
doi:10.1039/P29850000625 .

Došen-Mićović, Ljiljana, Žigman, Vida I., "Solvent effect on conformational equilibria. Solvation energy as a function of solute position and orientation within a cavity in a dielectric medium" in Journal of the Chemical Society, Perkin Transactions 2, no. 5 (1985):625-631,
https://doi.org/10.1039/P29850000625 . .

TY  - JOUR
AU  - Došen-Mićović, Ljiljana
AU  - Jeremić, Dragoslav
AU  - Allinger, Norman L.
PY  - 1983
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4218
AB  - A model of intramolecular electrostatic effects (called the induced dipole moment and energy (IDME) method) was derived by extending the method originally proposed by Del Re for calculating dipole moments and charge distributions. The IDME procedure consists of taking bond dipoles, calculated by the Del Re procedure, and allowing for nonadjacent dipole interactions by taking all components of bond polarizabilities into account. The method is applied to some simple halides, ketones, and ethers. The total dipole moments are well calculated and charge distributions reproduce many known trends. The calculated energies agree better with experiment overall than those calculated earlier by the modified Smith-Eyring method.
PB  - American Chemical Society (ACS)
T2  - Journal of the American Chemical Society
T1  - Treatment of electrostatic effects within the molecular mechanics method. 1
VL  - 105
IS  - 7
SP  - 1716
EP  - 1722
DO  - 10.1021/ja00345a003
ER  - 

@article{
author = "Došen-Mićović, Ljiljana and Jeremić, Dragoslav and Allinger, Norman L.",
year = "1983",
abstract = "A model of intramolecular electrostatic effects (called the induced dipole moment and energy (IDME) method) was derived by extending the method originally proposed by Del Re for calculating dipole moments and charge distributions. The IDME procedure consists of taking bond dipoles, calculated by the Del Re procedure, and allowing for nonadjacent dipole interactions by taking all components of bond polarizabilities into account. The method is applied to some simple halides, ketones, and ethers. The total dipole moments are well calculated and charge distributions reproduce many known trends. The calculated energies agree better with experiment overall than those calculated earlier by the modified Smith-Eyring method.",
publisher = "American Chemical Society (ACS)",
journal = "Journal of the American Chemical Society",
title = "Treatment of electrostatic effects within the molecular mechanics method. 1",
volume = "105",
number = "7",
pages = "1716-1722",
doi = "10.1021/ja00345a003"
}

Došen-Mićović, L., Jeremić, D.,& Allinger, N. L.. (1983). Treatment of electrostatic effects within the molecular mechanics method. 1. in Journal of the American Chemical Society
American Chemical Society (ACS)., 105(7), 1716-1722.
https://doi.org/10.1021/ja00345a003

Došen-Mićović L, Jeremić D, Allinger NL. Treatment of electrostatic effects within the molecular mechanics method. 1. in Journal of the American Chemical Society. 1983;105(7):1716-1722.
doi:10.1021/ja00345a003 .

Došen-Mićović, Ljiljana, Jeremić, Dragoslav, Allinger, Norman L., "Treatment of electrostatic effects within the molecular mechanics method. 1" in Journal of the American Chemical Society, 105, no. 7 (1983):1716-1722,
https://doi.org/10.1021/ja00345a003 . .

TY  - JOUR
AU  - Došen-Mićović, Ljiljana
AU  - Jeremić, Dragoslav
AU  - Allinger, Norman L.
PY  - 1983
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4428
AB  - The previously developed general method, which includes induction by dipoles in polarizable bonds and the solvation of molecular dipoles and quadrupoles, was used to calculate molecular dipole moments and to predict conformational equilibria of polar compounds, both in the gas phase and in solution. The results are in good agreement with experimentally determined values for 35 compounds including dihalides, halo ketones, and halo ethers. More simplified calculations often lead to erroneous predictions of conformational equilibria.
PB  - American Chemical Society
T2  - Journal of the American Chemical Society
T1  - Treatment of electrostatic effects within the molecular mechanics Method. 2
VL  - 105
IS  - 7
SP  - 1723
EP  - 1733
DO  - 10.1021/ja00345a004
ER  - 

@article{
author = "Došen-Mićović, Ljiljana and Jeremić, Dragoslav and Allinger, Norman L.",
year = "1983",
abstract = "The previously developed general method, which includes induction by dipoles in polarizable bonds and the solvation of molecular dipoles and quadrupoles, was used to calculate molecular dipole moments and to predict conformational equilibria of polar compounds, both in the gas phase and in solution. The results are in good agreement with experimentally determined values for 35 compounds including dihalides, halo ketones, and halo ethers. More simplified calculations often lead to erroneous predictions of conformational equilibria.",
publisher = "American Chemical Society",
journal = "Journal of the American Chemical Society",
title = "Treatment of electrostatic effects within the molecular mechanics Method. 2",
volume = "105",
number = "7",
pages = "1723-1733",
doi = "10.1021/ja00345a004"
}

Došen-Mićović, L., Jeremić, D.,& Allinger, N. L.. (1983). Treatment of electrostatic effects within the molecular mechanics Method. 2. in Journal of the American Chemical Society
American Chemical Society., 105(7), 1723-1733.
https://doi.org/10.1021/ja00345a004

Došen-Mićović L, Jeremić D, Allinger NL. Treatment of electrostatic effects within the molecular mechanics Method. 2. in Journal of the American Chemical Society. 1983;105(7):1723-1733.
doi:10.1021/ja00345a004 .

Došen-Mićović, Ljiljana, Jeremić, Dragoslav, Allinger, Norman L., "Treatment of electrostatic effects within the molecular mechanics Method. 2" in Journal of the American Chemical Society, 105, no. 7 (1983):1723-1733,
https://doi.org/10.1021/ja00345a004 . .

TY  - JOUR
AU  - Došen-Mićović, Ljiljana
AU  - Jeremić, Dragoslav
AU  - Allinger, Norman L.
PY  - 1981
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4423
AB  - Two of the stereoisomers of the title compound were prepared and their dipole moments were measured. For the r-1,c-3-dichloro-t-5-methylcyclohexane, the free energy difference between conformers with axial-axial (aa) and equatorial-equatorial (ee) chlorines was measured by a variable temperature NMR method, and the value found was 1.3 ± 0.2 Kcal/mol-1 (in acetone) favoring the latter. Molecular mechanics studies show that the solvation energy and the electrostatics are of major importance in understanding this equilibrium. Calculations show the effect of the methyl group is essentially additive, and give for cis-1,3-dichlorocyclohexane itself ee{measured angle}aa DH+ 3.0 kcal mol-1 (acetone).
PB  - Elsevier
T2  - Tetrahedron
T1  - The conformational equilibrium of 1,3-dichloro-5-methylcyclohexane
VL  - 37
IS  - 20
SP  - 3455
EP  - 3461
DO  - 10.1016/S0040-4020(01)98859-3
ER  - 

@article{
author = "Došen-Mićović, Ljiljana and Jeremić, Dragoslav and Allinger, Norman L.",
year = "1981",
abstract = "Two of the stereoisomers of the title compound were prepared and their dipole moments were measured. For the r-1,c-3-dichloro-t-5-methylcyclohexane, the free energy difference between conformers with axial-axial (aa) and equatorial-equatorial (ee) chlorines was measured by a variable temperature NMR method, and the value found was 1.3 ± 0.2 Kcal/mol-1 (in acetone) favoring the latter. Molecular mechanics studies show that the solvation energy and the electrostatics are of major importance in understanding this equilibrium. Calculations show the effect of the methyl group is essentially additive, and give for cis-1,3-dichlorocyclohexane itself ee{measured angle}aa DH+ 3.0 kcal mol-1 (acetone).",
publisher = "Elsevier",
journal = "Tetrahedron",
title = "The conformational equilibrium of 1,3-dichloro-5-methylcyclohexane",
volume = "37",
number = "20",
pages = "3455-3461",
doi = "10.1016/S0040-4020(01)98859-3"
}

Došen-Mićović, L., Jeremić, D.,& Allinger, N. L.. (1981). The conformational equilibrium of 1,3-dichloro-5-methylcyclohexane. in Tetrahedron
Elsevier., 37(20), 3455-3461.
https://doi.org/10.1016/S0040-4020(01)98859-3

Došen-Mićović L, Jeremić D, Allinger NL. The conformational equilibrium of 1,3-dichloro-5-methylcyclohexane. in Tetrahedron. 1981;37(20):3455-3461.
doi:10.1016/S0040-4020(01)98859-3 .

Došen-Mićović, Ljiljana, Jeremić, Dragoslav, Allinger, Norman L., "The conformational equilibrium of 1,3-dichloro-5-methylcyclohexane" in Tetrahedron, 37, no. 20 (1981):3455-3461,
https://doi.org/10.1016/S0040-4020(01)98859-3 . .