TY  - JOUR
AU  - Suručić, Relja
AU  - Jevtić, Ivana
AU  - Stanojković, Tatjana
AU  - Popović-Đorđević, Jelena
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7215
AB  - With the increasing global burden of diabetes mellitus type 2, the search for the new drugs, with better pharmacological profile is continued. As a part of this surge, the synthesis, pharmacological in vitro and computational evaluation of five, simple carbamate derivatives, against carbohydrate digestive enzyme α-glucosidase, is disclosed herein. Results of the experimental and computational assessment indicated that examined carbamates deterred the activity of α-glucosidase with acceptable IC50 values ranging from 65.34 to 79.89 μM compared to a standard drug acarbose (109.71 μM). Similarly, the studied compounds displayed in silico binding affinity for α-glucosidase enzyme with significant binding energies. Preliminary toxicity profiles of studied carbamates against three cancerous cell lines indicated their poor activity, suggesting that significant structural modifications have to be made to improve their anticancer efficiency. Results of the present study indicate that the examined carbamates were able to virtually or experimentally interact with an important target of diabetes mellitus type 2. Additionally, a new pharmacophore model is proposed featuring hydrogen bond donating carbamate –NH group, hydrogen bond accepting carbamate –OCH3 group and hydrophobic stabilization of aromatic moieties.
AB  - Са порастом појаве дијабетеса типа 2 у свету, јавља се потрага за новим лековима са што ефикаснијим фармаколошким профилом. Као део овог истраживања, приказана је синтеза, фармаколошко in vitro и рачунарско испитивање пет карбамата једноставне структуре, као инхибитора – глукозидазе, ензима који учествује у дигестивном разлагању шећера. Резултати експерименталног испитивања показали су да испитивани карбамати инхибирају активност – глукозидазе са задовољавајућим IC50 вредностима у опсегу од 65,34 до 79,89 μM, а у поређењу са стандардним леком, акарбозом (109,71  μM). Такође, in silico методом добијене су значајне енергије везивања за активно место –  глукозидазе. У прелиминарном испитивању цитотксичности према три типа канцерозних ћелија, карбамати су показали лошу активност, сугеришући да су потребне значајне структурне промене за побољшање њиховог антиканцерозног дејства. Уопштено говорећи, резултати ове студије показали су да су испитивани карбамати успешно виртуелно и експериментално интераговали са важном метом код дијабетеса типа 2. Такође је предложен и нови фармакофорни модел за -глукозидазу, који укључује карбаматну –NH групу као донора водоничне везе, затим карбаматну –OCH3 групу као акцептора водоничне везе, а такође и стабилизујуће хидрофобне интеракције ароматичних прстенова.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Antidiabetic potential of simple carbamate derivatives: Comparative experimental and computational study
T1  - Антидијабетски потенцијал једноставних карбамата: компаративна експериментална и рачунарска студија
VL  - 88
IS  - 11
SP  - 1089
EP  - 1102
DO  - 10.2298/JSC220923058S
ER  - 

@article{
author = "Suručić, Relja and Jevtić, Ivana and Stanojković, Tatjana and Popović-Đorđević, Jelena",
year = "2023",
abstract = "With the increasing global burden of diabetes mellitus type 2, the search for the new drugs, with better pharmacological profile is continued. As a part of this surge, the synthesis, pharmacological in vitro and computational evaluation of five, simple carbamate derivatives, against carbohydrate digestive enzyme α-glucosidase, is disclosed herein. Results of the experimental and computational assessment indicated that examined carbamates deterred the activity of α-glucosidase with acceptable IC50 values ranging from 65.34 to 79.89 μM compared to a standard drug acarbose (109.71 μM). Similarly, the studied compounds displayed in silico binding affinity for α-glucosidase enzyme with significant binding energies. Preliminary toxicity profiles of studied carbamates against three cancerous cell lines indicated their poor activity, suggesting that significant structural modifications have to be made to improve their anticancer efficiency. Results of the present study indicate that the examined carbamates were able to virtually or experimentally interact with an important target of diabetes mellitus type 2. Additionally, a new pharmacophore model is proposed featuring hydrogen bond donating carbamate –NH group, hydrogen bond accepting carbamate –OCH3 group and hydrophobic stabilization of aromatic moieties., Са порастом појаве дијабетеса типа 2 у свету, јавља се потрага за новим лековима са што ефикаснијим фармаколошким профилом. Као део овог истраживања, приказана је синтеза, фармаколошко in vitro и рачунарско испитивање пет карбамата једноставне структуре, као инхибитора – глукозидазе, ензима који учествује у дигестивном разлагању шећера. Резултати експерименталног испитивања показали су да испитивани карбамати инхибирају активност – глукозидазе са задовољавајућим IC50 вредностима у опсегу од 65,34 до 79,89 μM, а у поређењу са стандардним леком, акарбозом (109,71  μM). Такође, in silico методом добијене су значајне енергије везивања за активно место –  глукозидазе. У прелиминарном испитивању цитотксичности према три типа канцерозних ћелија, карбамати су показали лошу активност, сугеришући да су потребне значајне структурне промене за побољшање њиховог антиканцерозног дејства. Уопштено говорећи, резултати ове студије показали су да су испитивани карбамати успешно виртуелно и експериментално интераговали са важном метом код дијабетеса типа 2. Такође је предложен и нови фармакофорни модел за -глукозидазу, који укључује карбаматну –NH групу као донора водоничне везе, затим карбаматну –OCH3 групу као акцептора водоничне везе, а такође и стабилизујуће хидрофобне интеракције ароматичних прстенова.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Antidiabetic potential of simple carbamate derivatives: Comparative experimental and computational study, Антидијабетски потенцијал једноставних карбамата: компаративна експериментална и рачунарска студија",
volume = "88",
number = "11",
pages = "1089-1102",
doi = "10.2298/JSC220923058S"
}

Suručić, R., Jevtić, I., Stanojković, T.,& Popović-Đorđević, J.. (2023). Antidiabetic potential of simple carbamate derivatives: Comparative experimental and computational study. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 88(11), 1089-1102.
https://doi.org/10.2298/JSC220923058S

Suručić R, Jevtić I, Stanojković T, Popović-Đorđević J. Antidiabetic potential of simple carbamate derivatives: Comparative experimental and computational study. in Journal of the Serbian Chemical Society. 2023;88(11):1089-1102.
doi:10.2298/JSC220923058S .

Suručić, Relja, Jevtić, Ivana, Stanojković, Tatjana, Popović-Đorđević, Jelena, "Antidiabetic potential of simple carbamate derivatives: Comparative experimental and computational study" in Journal of the Serbian Chemical Society, 88, no. 11 (2023):1089-1102,
https://doi.org/10.2298/JSC220923058S . .

TY  - JOUR
AU  - Krunić, Mihajlo
AU  - Penjišević, Jelena
AU  - Suručić, Relja
AU  - Šegan, Sandra
AU  - Kostić-Rajačić, Slađana
AU  - Jevtić, Ivana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5634
AB  - Fourteen novel N-benzylpiperidine and N,N-diarylpiperazine conjugates were synthesized and pharmacologically evaluated as donepezil analogs, in a ligand-based drug design approach. All compounds possessed high to moderate in vitro inhibitory activity with IC50 in range 2.3–20 µM and selectivity towards acetylcholinesterase, while being inactive towards butyrylcholinesterase. Structure-activity relationship analysis revealed the influence of N,N-diarylpiperazine moiety and the linker connecting two pharmacophores on the inhibitory activity. Kinetic studies on the two most active compounds 7g and 8g (IC50 = 2.3 and 4 µM, respectively) revealed mixed type mode of inhibition, binding to both, free enzyme and enzyme-substrate complex. For further understanding of mechanism of action and binding orientations, molecular docking was performed for all compounds, while the ligand transport simulation and molecular dynamics simulations were performed for 7g and 8g. Computational results corroborated well with in vitro activities and kinetic studies.
PB  - Elsevier B.V.
T2  - Journal of Molecular Structure
T1  - Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors
VL  - 1276
SP  - 134809
DO  - 10.1016/j.molstruc.2022.134809
ER  - 

@article{
author = "Krunić, Mihajlo and Penjišević, Jelena and Suručić, Relja and Šegan, Sandra and Kostić-Rajačić, Slađana and Jevtić, Ivana",
year = "2023",
abstract = "Fourteen novel N-benzylpiperidine and N,N-diarylpiperazine conjugates were synthesized and pharmacologically evaluated as donepezil analogs, in a ligand-based drug design approach. All compounds possessed high to moderate in vitro inhibitory activity with IC50 in range 2.3–20 µM and selectivity towards acetylcholinesterase, while being inactive towards butyrylcholinesterase. Structure-activity relationship analysis revealed the influence of N,N-diarylpiperazine moiety and the linker connecting two pharmacophores on the inhibitory activity. Kinetic studies on the two most active compounds 7g and 8g (IC50 = 2.3 and 4 µM, respectively) revealed mixed type mode of inhibition, binding to both, free enzyme and enzyme-substrate complex. For further understanding of mechanism of action and binding orientations, molecular docking was performed for all compounds, while the ligand transport simulation and molecular dynamics simulations were performed for 7g and 8g. Computational results corroborated well with in vitro activities and kinetic studies.",
publisher = "Elsevier B.V.",
journal = "Journal of Molecular Structure",
title = "Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors",
volume = "1276",
pages = "134809",
doi = "10.1016/j.molstruc.2022.134809"
}

Krunić, M., Penjišević, J., Suručić, R., Šegan, S., Kostić-Rajačić, S.,& Jevtić, I.. (2023). Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors. in Journal of Molecular Structure
Elsevier B.V.., 1276, 134809.
https://doi.org/10.1016/j.molstruc.2022.134809

Krunić M, Penjišević J, Suručić R, Šegan S, Kostić-Rajačić S, Jevtić I. Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors. in Journal of Molecular Structure. 2023;1276:134809.
doi:10.1016/j.molstruc.2022.134809 .

Krunić, Mihajlo, Penjišević, Jelena, Suručić, Relja, Šegan, Sandra, Kostić-Rajačić, Slađana, Jevtić, Ivana, "Structure-activity and binding orientations analysis of potent, newly synthesized, acetylcholinesterase inhibitors" in Journal of Molecular Structure, 1276 (2023):134809,
https://doi.org/10.1016/j.molstruc.2022.134809 . .

TY  - CONF
AU  - Jevtić, Ivana
AU  - Andrić, Deana
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Dukic-Stefanovic, Sladjana
AU  - Kostić-Rajačić, Slađana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5851
AB  - Serotonin 5HT1a receptors belongs to a class G-protein coupled receptors and it is widely recognized as one of the targets for treating neurological disorders such depression and schizophrenia. N-arylpiperazine structural motif is present in many compounds with pronounced 5HT1a activity including recently approved aripiprazole for the treatment of the major depressive disorder.
PB  - European Federation for Medicinal chemistry and Chemical biology (EFMC)
C3  - Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France
T1  - Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands
SP  - 66
EP  - 66
UR  - https://hdl.handle.net/21.15107/rcub_cer_5851
ER  - 

@conference{
author = "Jevtić, Ivana and Andrić, Deana and Penjišević, Jelena and Šukalović, Vladimir and Dukic-Stefanovic, Sladjana and Kostić-Rajačić, Slađana",
year = "2022",
abstract = "Serotonin 5HT1a receptors belongs to a class G-protein coupled receptors and it is widely recognized as one of the targets for treating neurological disorders such depression and schizophrenia. N-arylpiperazine structural motif is present in many compounds with pronounced 5HT1a activity including recently approved aripiprazole for the treatment of the major depressive disorder.",
publisher = "European Federation for Medicinal chemistry and Chemical biology (EFMC)",
journal = "Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France",
title = "Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands",
pages = "66-66",
url = "https://hdl.handle.net/21.15107/rcub_cer_5851"
}

Jevtić, I., Andrić, D., Penjišević, J., Šukalović, V., Dukic-Stefanovic, S.,& Kostić-Rajačić, S.. (2022). Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands. in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France
European Federation for Medicinal chemistry and Chemical biology (EFMC)., 66-66.
https://hdl.handle.net/21.15107/rcub_cer_5851

Jevtić I, Andrić D, Penjišević J, Šukalović V, Dukic-Stefanovic S, Kostić-Rajačić S. Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands. in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France. 2022;:66-66.
https://hdl.handle.net/21.15107/rcub_cer_5851 .

Jevtić, Ivana, Andrić, Deana, Penjišević, Jelena, Šukalović, Vladimir, Dukic-Stefanovic, Sladjana, Kostić-Rajačić, Slađana, "Structure-activity relationship, docking analysis and ADME  properties of newly designed, potent serotonin 5HT1a receptor ligands" in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France (2022):66-66,
https://hdl.handle.net/21.15107/rcub_cer_5851 .

TY  - CONF
AU  - Krunić, Mihajlo
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Kostić-Rajačić, Slađana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5850
AB  - Alzheimer's disease (AD) is a serious, neurodegenerative disease, characterized with a progressive loss of cognitive and behavioral functions leading to fatal outcome. Tacrine belongs to a class of cholinesterase inhibitors(ChEls) and it is the first ChEI marketed for the treatment of AD symptoms.
PB  - European Federation for Medicinal chemistry and Chemical biology (EFMC)
C3  - Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France
T1  - Novel multitarget tacrine derivatives: design and structure activity relationship
SP  - P013
UR  - https://hdl.handle.net/21.15107/rcub_cer_5850
ER  - 

@conference{
author = "Krunić, Mihajlo and Jevtić, Ivana and Penjišević, Jelena and Kostić-Rajačić, Slađana",
year = "2022",
abstract = "Alzheimer's disease (AD) is a serious, neurodegenerative disease, characterized with a progressive loss of cognitive and behavioral functions leading to fatal outcome. Tacrine belongs to a class of cholinesterase inhibitors(ChEls) and it is the first ChEI marketed for the treatment of AD symptoms.",
publisher = "European Federation for Medicinal chemistry and Chemical biology (EFMC)",
journal = "Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France",
title = "Novel multitarget tacrine derivatives: design and structure activity relationship",
pages = "P013",
url = "https://hdl.handle.net/21.15107/rcub_cer_5850"
}

Krunić, M., Jevtić, I., Penjišević, J.,& Kostić-Rajačić, S.. (2022). Novel multitarget tacrine derivatives: design and structure activity relationship. in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France
European Federation for Medicinal chemistry and Chemical biology (EFMC)., P013.
https://hdl.handle.net/21.15107/rcub_cer_5850

Krunić M, Jevtić I, Penjišević J, Kostić-Rajačić S. Novel multitarget tacrine derivatives: design and structure activity relationship. in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France. 2022;:P013.
https://hdl.handle.net/21.15107/rcub_cer_5850 .

Krunić, Mihajlo, Jevtić, Ivana, Penjišević, Jelena, Kostić-Rajačić, Slađana, "Novel multitarget tacrine derivatives: design and structure activity relationship" in Book of abstracts - EFMC-YMCS-Young Medicinal Chemists' Symposium, September 8-9, 2022, Nice, France (2022):P013,
https://hdl.handle.net/21.15107/rcub_cer_5850 .

TY  - JOUR
AU  - Krunić, Mihajlo
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Kostić Rajačić, Slađana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4972
AB  - The synthetic route toward novel tricyclic, nitrogen-containing system is disclosed. Three novel compounds possessing structural features of 1,2,3,4-tetrahydroquinoxaline and decahydropyrido[3,4-b]pyrazine are synthesized starting from readily available precursors in six or seven steps, of which the last three or four steps respectively are diastereoselective. Key reaction steps include N-acylation, Hofmann rearrangement and ring-closing Buchwald– Hartwig reaction. Compounds trans-8, cis-12 and trans-12 are synthesized in order to prove that this novel, tricyclic system can be functionalized with various groups. Synthetic significance of this heterocyclic system lies in the possibility for the orthogonal functionalization of three different amino groups, allowing fine structural tuning.
AB  - У овом раду представљена је синтеза новог трицикличног система који садржи азот.  Три нова једињења код којих су комбиноване структурне карактеристике 1,2,3,4-тетрахидрохиноксалина и декахидропиридо[3,4-b]пиразина, добијена су полазећи од лако доступних прекурсора, у шест или седам фаза од којих су последње три или четири,  редом, диастереоселективне. Кључне синтетичке трансформације укључују N-ациловање, Hofmann премештање и интрамолекулску Buchwald–Hartwig реакцију, као фазу у којој долази до циклизације. Једињења trans-8, cis-12 и trans-12 су синтетисана како би се представила могућност функционализације новог трицикличног система. Синтетички значај новог хетероцикличног система представљен је у могућности ортогоналне функционализације три различите амино групе, чиме се може постићи фино подешавање структуре.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system
T1  - Синтетски пут за добијање 1,2,3,4-тетрахидрохиноксалинскo/пиперидинског трицикличног система
VL  - 87
IS  - 2
SP  - 169
EP  - 179
DO  - 10.2298/JSC210416068K
ER  - 

@article{
author = "Krunić, Mihajlo and Jevtić, Ivana and Penjišević, Jelena and Kostić Rajačić, Slađana",
year = "2022",
abstract = "The synthetic route toward novel tricyclic, nitrogen-containing system is disclosed. Three novel compounds possessing structural features of 1,2,3,4-tetrahydroquinoxaline and decahydropyrido[3,4-b]pyrazine are synthesized starting from readily available precursors in six or seven steps, of which the last three or four steps respectively are diastereoselective. Key reaction steps include N-acylation, Hofmann rearrangement and ring-closing Buchwald– Hartwig reaction. Compounds trans-8, cis-12 and trans-12 are synthesized in order to prove that this novel, tricyclic system can be functionalized with various groups. Synthetic significance of this heterocyclic system lies in the possibility for the orthogonal functionalization of three different amino groups, allowing fine structural tuning., У овом раду представљена је синтеза новог трицикличног система који садржи азот.  Три нова једињења код којих су комбиноване структурне карактеристике 1,2,3,4-тетрахидрохиноксалина и декахидропиридо[3,4-b]пиразина, добијена су полазећи од лако доступних прекурсора, у шест или седам фаза од којих су последње три или четири,  редом, диастереоселективне. Кључне синтетичке трансформације укључују N-ациловање, Hofmann премештање и интрамолекулску Buchwald–Hartwig реакцију, као фазу у којој долази до циклизације. Једињења trans-8, cis-12 и trans-12 су синтетисана како би се представила могућност функционализације новог трицикличног система. Синтетички значај новог хетероцикличног система представљен је у могућности ортогоналне функционализације три различите амино групе, чиме се може постићи фино подешавање структуре.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system, Синтетски пут за добијање 1,2,3,4-тетрахидрохиноксалинскo/пиперидинског трицикличног система",
volume = "87",
number = "2",
pages = "169-179",
doi = "10.2298/JSC210416068K"
}

Krunić, M., Jevtić, I., Penjišević, J.,& Kostić Rajačić, S.. (2022). Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 87(2), 169-179.
https://doi.org/10.2298/JSC210416068K

Krunić M, Jevtić I, Penjišević J, Kostić Rajačić S. Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system. in Journal of the Serbian Chemical Society. 2022;87(2):169-179.
doi:10.2298/JSC210416068K .

Krunić, Mihajlo, Jevtić, Ivana, Penjišević, Jelena, Kostić Rajačić, Slađana, "Synthetic route towards 1,2,3,4-tetrahydroquinoxaline/piperidine combined tricyclic ring system" in Journal of the Serbian Chemical Society, 87, no. 2 (2022):169-179,
https://doi.org/10.2298/JSC210416068K . .

TY  - JOUR
AU  - Šegan, Sandra
AU  - Jevtić, Ivana
AU  - Tosti, Tomislav
AU  - Penjišević, Jelena
AU  - Šukalović, Vladimir
AU  - Kostić Rajačić, Slađana
AU  - Milojković-Opsenica, Dušanka
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5413
AB  - Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin-layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diastereomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lipophilicity, expressed as retention indices RM0, b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte's retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and molecular weight. In general, results of the present research corroborate well with previously determined antinociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design.
PB  - Elsevier
T2  - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
T1  - Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography
VL  - 1211
SP  - 123481
DO  - 10.1016/j.jchromb.2022.123481
ER  - 

@article{
author = "Šegan, Sandra and Jevtić, Ivana and Tosti, Tomislav and Penjišević, Jelena and Šukalović, Vladimir and Kostić Rajačić, Slađana and Milojković-Opsenica, Dušanka",
year = "2022",
abstract = "Lipophilicity and ionization constant of sixteen fentanyl analogues were investigated by reversed-phase thin-layer chromatography (RP-TLC). Fourteen compounds have nitrogen containing groups at C-3 position of the piperidine ring and two compounds are 3-carbomethoxy derivatives of fentanyl. Among them, five are diastereomeric cis/trans couples and six novel trans diastereomers. In addition, the lipophilicity and ionization constant of fentanyl were also determined by the same method, as a reference. The physicochemical property, lipophilicity, expressed as retention indices RM0, b, and C0, as well as PC1, was determined and correlated with in silico values. Ionization constants were determined on the basis of the relationships between analyte's retention expressed as RF and mobile phase pH. Calculated structural descriptors together with the retention indices, were subjected to the principal component analysis – PCA and hierarchical cluster analysis – HCA, in order to provide basic insights into the similarities among the studied compounds. The blood – brain barrier (BBB) permeation was investigated in the function of experimentally obtained values of lipophilicity, polar surface area and molecular weight. In general, results of the present research corroborate well with previously determined antinociceptive activities of the investigated compounds, pointing out that besides the cis/trans isomerism, another set of important parameters should be taken into account when designing new derivatives of C-3 substituted fentanyl, especially lipophilicity, voluminosity and HBD/A character of the substituents. Accordingly, RP-TLC can be considered as a valuable asset in the ligand-based drug design.",
publisher = "Elsevier",
journal = "Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences",
title = "Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography",
volume = "1211",
pages = "123481",
doi = "10.1016/j.jchromb.2022.123481"
}

Šegan, S., Jevtić, I., Tosti, T., Penjišević, J., Šukalović, V., Kostić Rajačić, S.,& Milojković-Opsenica, D.. (2022). Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography. in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Elsevier., 1211, 123481.
https://doi.org/10.1016/j.jchromb.2022.123481

Šegan S, Jevtić I, Tosti T, Penjišević J, Šukalović V, Kostić Rajačić S, Milojković-Opsenica D. Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography. in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2022;1211:123481.
doi:10.1016/j.jchromb.2022.123481 .

Šegan, Sandra, Jevtić, Ivana, Tosti, Tomislav, Penjišević, Jelena, Šukalović, Vladimir, Kostić Rajačić, Slađana, Milojković-Opsenica, Dušanka, "Determination of lipophilicity and ionization of fentanyl and its 3‑substituted analogs by reversed-phase thin-layer chromatography" in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1211 (2022):123481,
https://doi.org/10.1016/j.jchromb.2022.123481 . .

TY  - CONF
AU  - Andrić, Deana
AU  - Dukic-Stefanovic, Sladjana
AU  - Penjišević, Jelena
AU  - Jevtić, Ivana
AU  - Šukalović, Vladimir
AU  - Suručić, Relja
AU  - Kostić-Rajačić, Slađana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5849
AB  - 5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric
disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of
new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand
aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations,
revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine
selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro
pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c)
with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM,
respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c
possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological
results are therefore in accordance with the molecular docking simulations thus proving the rational
design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new,
potential antidepressants.
PB  - Kragujevac : Institute for Information Technologies
C3  - Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac
T1  - Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides
SP  - 355
EP  - 358
DO  - 10.46793/ICCBI21.355A
ER  - 

@conference{
author = "Andrić, Deana and Dukic-Stefanovic, Sladjana and Penjišević, Jelena and Jevtić, Ivana and Šukalović, Vladimir and Suručić, Relja and Kostić-Rajačić, Slađana",
year = "2021",
abstract = "5HT1A receptor targeting drugs have been used as the treatment for the many neuropsychiatric
disorders, such as schizophrenia and depression. As a part of ongoing research, we designed series of
new compounds that share arylpiperazine common structural motif with the 5HT1A receptor ligand
aripiprazole. Receptor-ligand interactions were determined by the molecular docking simulations,
revealing the positive impact of the phenyl substitution in the arylpiperazine part of the molecules. Nine
selected compounds were synthesized in four reaction steps in high overall yields (59-73%). In vitro
pharmacological evaluation of the synthesized compounds revealed three compounds (5b, 6b and 6c)
with high 5HT1A binding affinity, comparable with aripiprazole (Ki 12.0, 4.8, 12.8, 5.6 nM,
respectively). Compounds from b series, 5b and 6b, possess 2-methoxyphenyl substituents, while 6c
possess 2,3-dichlorophenyl substituent in the arylpiperazine part of the molecule. The pharmacological
results are therefore in accordance with the molecular docking simulations thus proving the rational
design. Compounds 5c, 6b and 6c can be considered as the candidates for further evaluation as new,
potential antidepressants.",
publisher = "Kragujevac : Institute for Information Technologies",
journal = "Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac",
title = "Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides",
pages = "355-358",
doi = "10.46793/ICCBI21.355A"
}

Andrić, D., Dukic-Stefanovic, S., Penjišević, J., Jevtić, I., Šukalović, V., Suručić, R.,& Kostić-Rajačić, S.. (2021). Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac
Kragujevac : Institute for Information Technologies., 355-358.
https://doi.org/10.46793/ICCBI21.355A

Andrić D, Dukic-Stefanovic S, Penjišević J, Jevtić I, Šukalović V, Suručić R, Kostić-Rajačić S. Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides. in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac. 2021;:355-358.
doi:10.46793/ICCBI21.355A .

Andrić, Deana, Dukic-Stefanovic, Sladjana, Penjišević, Jelena, Jevtić, Ivana, Šukalović, Vladimir, Suručić, Relja, Kostić-Rajačić, Slađana, "Design, Synthesis and Pharmacological Evaluation of novel N-{4-[2-(4-aryl-piperazin-1-yl)-ethyl]-phenyl}-arylamides" in Book of proceedings - 1st International Conference on Chemo and Bioinformatics, October 26-27, 2021. Kragujevac (2021):355-358,
https://doi.org/10.46793/ICCBI21.355A . .

TY  - JOUR
AU  - Dukić-Stefanović, Sladjana
AU  - Lai, Thu Hang
AU  - Toussaint, Magali
AU  - Clauß, Oliver
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Andrić, Deana
AU  - Ludwig, Friedrich-Alexander
AU  - Gündel, Daniel
AU  - Deuther-Conrad, Winnie
AU  - Kostić Rajačić, Slađana
AU  - Brust, Peter
AU  - Teodoro, Rodrigo
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4756
AB  - Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson's disease, Alzheimer's disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder L-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (Ki MAO-B = 6 nM), an automated copper-mediated radiofluorination starting from the pinacol boronic ester 17 is described. An in vitro screening in different species revealed a MAO-B region-specific accumulation of [18F]6 in rats and piglets in comparison to L-[3H]deprenyl. The pre-clinical in vivo assessment of [18F]6 in mice demonstrated the potential of indanones to readily cross the blood–brain barrier. Nonetheless, parallel in vivo metabolism studies indicated the presence of blood–brain barrier metabolites, thus arguing for further structural modifications. With the matching analytical profiles of the radiometabolite analysis from the in vitro liver microsome studies and the in vivo evaluation, the structure's elucidation of the blood–brain barrier penetrant radiometabolites is possible and will serve as basis for the development of new indanone derivatives suitable for the PET imaging of MAO-B.
PB  - Elsevier
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain
VL  - 48
SP  - 128254
DO  - 10.1016/j.bmcl.2021.128254
ER  - 

@article{
author = "Dukić-Stefanović, Sladjana and Lai, Thu Hang and Toussaint, Magali and Clauß, Oliver and Jevtić, Ivana and Penjišević, Jelena and Andrić, Deana and Ludwig, Friedrich-Alexander and Gündel, Daniel and Deuther-Conrad, Winnie and Kostić Rajačić, Slađana and Brust, Peter and Teodoro, Rodrigo",
year = "2021",
abstract = "Monoamine oxidases (MAOs) play a key role in the metabolism of major monoamine neurotransmitters. In particular, the upregulation of MAO-B in Parkinson's disease, Alzheimer's disease and cancer augmented the development of selective MAO-B inhibitors for diagnostic and therapeutic purposes, such as the anti-parkinsonian MAO-B irreversible binder L-deprenyl (Selegiline®). Herein we report on the synthesis of novel fluorinated indanone derivatives for PET imaging of MAO-B in the brain. Out of our series, the derivatives 6, 8, 9 and 13 are amongst the most affine and selective ligands for MAO-B reported so far. For the derivative 6-((3-fluorobenzyl)oxy)-2,3-dihydro-1H-inden-1-one (6) exhibiting an outstanding affinity (Ki MAO-B = 6 nM), an automated copper-mediated radiofluorination starting from the pinacol boronic ester 17 is described. An in vitro screening in different species revealed a MAO-B region-specific accumulation of [18F]6 in rats and piglets in comparison to L-[3H]deprenyl. The pre-clinical in vivo assessment of [18F]6 in mice demonstrated the potential of indanones to readily cross the blood–brain barrier. Nonetheless, parallel in vivo metabolism studies indicated the presence of blood–brain barrier metabolites, thus arguing for further structural modifications. With the matching analytical profiles of the radiometabolite analysis from the in vitro liver microsome studies and the in vivo evaluation, the structure's elucidation of the blood–brain barrier penetrant radiometabolites is possible and will serve as basis for the development of new indanone derivatives suitable for the PET imaging of MAO-B.",
publisher = "Elsevier",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain",
volume = "48",
pages = "128254",
doi = "10.1016/j.bmcl.2021.128254"
}

Dukić-Stefanović, S., Lai, T. H., Toussaint, M., Clauß, O., Jevtić, I., Penjišević, J., Andrić, D., Ludwig, F., Gündel, D., Deuther-Conrad, W., Kostić Rajačić, S., Brust, P.,& Teodoro, R.. (2021). In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain. in Bioorganic and Medicinal Chemistry Letters
Elsevier., 48, 128254.
https://doi.org/10.1016/j.bmcl.2021.128254

Dukić-Stefanović S, Lai TH, Toussaint M, Clauß O, Jevtić I, Penjišević J, Andrić D, Ludwig F, Gündel D, Deuther-Conrad W, Kostić Rajačić S, Brust P, Teodoro R. In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain. in Bioorganic and Medicinal Chemistry Letters. 2021;48:128254.
doi:10.1016/j.bmcl.2021.128254 .

Dukić-Stefanović, Sladjana, Lai, Thu Hang, Toussaint, Magali, Clauß, Oliver, Jevtić, Ivana, Penjišević, Jelena, Andrić, Deana, Ludwig, Friedrich-Alexander, Gündel, Daniel, Deuther-Conrad, Winnie, Kostić Rajačić, Slađana, Brust, Peter, Teodoro, Rodrigo, "In vitro and in vivo evaluation of fluorinated indanone derivatives as potential positron emission tomography agents for the imaging of monoamine oxidase B in the brain" in Bioorganic and Medicinal Chemistry Letters, 48 (2021):128254,
https://doi.org/10.1016/j.bmcl.2021.128254 . .

TY  - CONF
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Kostić-Rajačić, Slađana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5837
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disorder characterized by deterioration of
cognitive skills and it is the most abundant form of dementia according to the World Health Organization
(WHO).1 Tacrine belongs to a class of acetylcholinesterase inhibitors (AChEIs) and it was formerly used in the
treatment of AD symptoms. Albeit no longer in clinical use due to its hepatotoxicity, tacrine ring system is
extensively investigated as pharmacophore in novel AChEIs, many of which showed improved pharmacological
profile in the preclinical studies.2 Here we present optimized synthetic pathway and pharmacological evaluation
of three novel tacrine derivatives (5, 6 and 7), possessing functionalized piperidine connected with tacrine via
five methylene groups alkyl chain
PB  - The Société de Chimie Thérapeutique (SCT) / French Medicinal Chemistry Society
C3  - Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event
T1  - Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors
SP  - 119
EP  - 119
UR  - https://hdl.handle.net/21.15107/rcub_cer_5837
ER  - 

@conference{
author = "Jevtić, Ivana and Penjišević, Jelena and Kostić-Rajačić, Slađana",
year = "2021",
abstract = "Alzheimer's disease (AD) is a progressive, neurodegenerative disorder characterized by deterioration of
cognitive skills and it is the most abundant form of dementia according to the World Health Organization
(WHO).1 Tacrine belongs to a class of acetylcholinesterase inhibitors (AChEIs) and it was formerly used in the
treatment of AD symptoms. Albeit no longer in clinical use due to its hepatotoxicity, tacrine ring system is
extensively investigated as pharmacophore in novel AChEIs, many of which showed improved pharmacological
profile in the preclinical studies.2 Here we present optimized synthetic pathway and pharmacological evaluation
of three novel tacrine derivatives (5, 6 and 7), possessing functionalized piperidine connected with tacrine via
five methylene groups alkyl chain",
publisher = "The Société de Chimie Thérapeutique (SCT) / French Medicinal Chemistry Society",
journal = "Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event",
title = "Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors",
pages = "119-119",
url = "https://hdl.handle.net/21.15107/rcub_cer_5837"
}

Jevtić, I., Penjišević, J.,& Kostić-Rajačić, S.. (2021). Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors. in Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event
The Société de Chimie Thérapeutique (SCT) / French Medicinal Chemistry Society., 119-119.
https://hdl.handle.net/21.15107/rcub_cer_5837

Jevtić I, Penjišević J, Kostić-Rajačić S. Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors. in Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event. 2021;:119-119.
https://hdl.handle.net/21.15107/rcub_cer_5837 .

Jevtić, Ivana, Penjišević, Jelena, Kostić-Rajačić, Slađana, "Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors" in Book of abstracts - 56th International conference on medicinal chemistry, RICT 2021, "Interfacing chemical biology and drug discovery",  July 7-9, 2021, virtual event (2021):119-119,
https://hdl.handle.net/21.15107/rcub_cer_5837 .

TY  - CONF
AU  - Krunić, Mihajlo
AU  - Penjišević, Jelena
AU  - Jevtić, Ivana
AU  - Ivanović, Milovan
AU  - Kostić-Rajačić, Slađana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5843
AB  - Alzheimer’s disease (AD) is a neurodegenerative disease which affects over 50 milion people worldwide.1) AD
mainly affects people ages 65 and above. Symptoms are memory loss, decline in learning capacity, and language
problems. One of currently available treatments for Alzheimer's disease consists of Cholinesterase (ChEIs)
inhibitors, which raise acetylcholine levels in the brain. The drugs currently approved by the FDA for this
purpose are donepezil, rivastigmine and galantamine.
As a part of our research we designed and synthesized seven novel compounds (6a-g) as potential
acetylcholinesterase inhibitors (AChEIs). The compounds contain N-benzyl piperidine moiety, which is common
in many inhibitors including donepezil,2) and N-aryl piperazine moieties.
PB  - Division of Medicinal  Chemistry and Chemical Biology of the Swiss Chemical  Society
PB  - European Federation  for Medicinal Chemistry and Chemical Biology (EFMC)
C3  - Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event
T1  - Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors
SP  - 413
EP  - 413
UR  - https://hdl.handle.net/21.15107/rcub_cer_5843
ER  - 

@conference{
author = "Krunić, Mihajlo and Penjišević, Jelena and Jevtić, Ivana and Ivanović, Milovan and Kostić-Rajačić, Slađana",
year = "2021",
abstract = "Alzheimer’s disease (AD) is a neurodegenerative disease which affects over 50 milion people worldwide.1) AD
mainly affects people ages 65 and above. Symptoms are memory loss, decline in learning capacity, and language
problems. One of currently available treatments for Alzheimer's disease consists of Cholinesterase (ChEIs)
inhibitors, which raise acetylcholine levels in the brain. The drugs currently approved by the FDA for this
purpose are donepezil, rivastigmine and galantamine.
As a part of our research we designed and synthesized seven novel compounds (6a-g) as potential
acetylcholinesterase inhibitors (AChEIs). The compounds contain N-benzyl piperidine moiety, which is common
in many inhibitors including donepezil,2) and N-aryl piperazine moieties.",
publisher = "Division of Medicinal  Chemistry and Chemical Biology of the Swiss Chemical  Society, European Federation  for Medicinal Chemistry and Chemical Biology (EFMC)",
journal = "Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event",
title = "Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors",
pages = "413-413",
url = "https://hdl.handle.net/21.15107/rcub_cer_5843"
}

Krunić, M., Penjišević, J., Jevtić, I., Ivanović, M.,& Kostić-Rajačić, S.. (2021). Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors. in Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event
Division of Medicinal  Chemistry and Chemical Biology of the Swiss Chemical  Society., 413-413.
https://hdl.handle.net/21.15107/rcub_cer_5843

Krunić M, Penjišević J, Jevtić I, Ivanović M, Kostić-Rajačić S. Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors. in Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event. 2021;:413-413.
https://hdl.handle.net/21.15107/rcub_cer_5843 .

Krunić, Mihajlo, Penjišević, Jelena, Jevtić, Ivana, Ivanović, Milovan, Kostić-Rajačić, Slađana, "Synthesis and pharmacology evaluation of novel 1-benzyl-n-(4-(4-arylpiperazin-1-yl)phenyl)piperidin-4-carboxamides, as potential acetylcholinesterase inhibitors" in Book of Abstracts - 26th EFMC-ISMC, International Symposium on Medicinal Chemistry, Aug. 29-Sept. 2, 2021, virtual event (2021):413-413,
https://hdl.handle.net/21.15107/rcub_cer_5843 .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Savić Vujović, Katarina
AU  - Srebro, Dragana
AU  - Vučković, Sonja
AU  - Ivanović, Milovan D.
AU  - Kostić Rajačić, Slađana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3591
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 Nature
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 and Savić Vujović, Katarina and Srebro, Dragana and Vučković, Sonja and Ivanović, Milovan D. 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 Nature",
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., Savić Vujović, K., Srebro, D., Vučković, S., Ivanović, M. D.,& Kostić Rajačić, S.. (2020). Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines. in Pharmacological Reports
Springer Nature., 72(4), 1069-1075.
https://doi.org/10.1007/s43440-020-00121-2

Jevtić I, Savić Vujović K, Srebro D, Vučković S, Ivanović MD, 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, Savić Vujović, Katarina, Srebro, Dragana, Vučković, Sonja, Ivanović, Milovan D., 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 . .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Savić Vujović, Katarina
AU  - Srebro, Dragana
AU  - Vučković, Sonja
AU  - Ivanović, Milovan D.
AU  - Kostić Rajačić, Slađana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3591
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3592
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 Nature
T2  - Pharmacological Reports
T1  - Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines
DO  - 10.1007/s43440-020-00121-2
ER  - 

@article{
author = "Jevtić, Ivana and Savić Vujović, Katarina and Srebro, Dragana and Vučković, Sonja and Ivanović, Milovan D. 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 Nature",
journal = "Pharmacological Reports",
title = "Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines",
doi = "10.1007/s43440-020-00121-2"
}

Jevtić, I., Savić Vujović, K., Srebro, D., Vučković, S., Ivanović, M. D.,& Kostić Rajačić, S.. (2020). Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines. in Pharmacological Reports
Springer Nature..
https://doi.org/10.1007/s43440-020-00121-2

Jevtić I, Savić Vujović K, Srebro D, Vučković S, Ivanović MD, Kostić Rajačić S. Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines. in Pharmacological Reports. 2020;.
doi:10.1007/s43440-020-00121-2 .

Jevtić, Ivana, Savić Vujović, Katarina, Srebro, Dragana, Vučković, Sonja, Ivanović, Milovan D., Kostić Rajačić, Slađana, "Synthesis and pharmacological evaluation of novel cis and trans 3‑substituted anilidopiperidines" in Pharmacological Reports (2020),
https://doi.org/10.1007/s43440-020-00121-2 . .

TY  - THES
AU  - Jevtić, Ivana
PY  - 2020
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=7699
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:22906/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=24288009
UR  - https://nardus.mpn.gov.rs/handle/123456789/17614
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3737
AB  - U okviru ove disertacije dizajnirano je 30 anilidopipredina, analoga jakog -opioidnog agonista i kliničkog analgetika fentanila. Razvijen je efikasan sintetički put za njihovo dobijanje, a sintetisana jedinjenja mogu se podeliti u dve serije. U okviru prve serije sintetisano je 13 novih analoga fentanila sa različitim azotnim grupama u položaju C3 piperidinskog prstena. Takođe je optimizovana sinteza dva prethodno sintetisana biciklična analoga fentanila. Jedinjenja prve serije predstavljaju prve poznate analoge fentanila sa azotnim grupama u položaju C3. U okviru druge serije sintetisano je 15 novih analoga fentanila, koji su u položaju N1 povezani sa pojedinim N-arilpiperazinima preko linearnih alkil mostova različitih dužina. Jedinjenja druge serije dizajnirana su da budu potencijalni heterobivalenti ligandi, jer sadrže anilidopiperidinsko jezgro fentanila kao -opioidnu agonističku farmakoforu, a N-arilpiperazin kao D2-dopaminergičku, agonističku farmakoforu.Analgetička aktivnost svih 30 jedinjenja ispitana je in vivo. Samo četiri jedinjenja, sva iz prve serije, pokazala su analgetičku aktivnost. Najaktivnije jedinjenje, oko 1,8 puta manje aktivno od fentanila, karakterišu brzo i kratko dejstvo analgetičkog efekta, pa se stoga može potencijalno iskoristiti u različitim farmacutskim formulacijama za tretman bola. Afinitet vezivanja jedinjenja druge serije za dopaminergčke D2 receptore ispitan je in vitro testovima kompeticije koristeći 3H spiperon kao radioaktivni ligand. Odsustvo analgetičke aktivnosti i slab afinitet vezivanja za dopaminergičke D2 receptore, ukazuje da jedinjenja druge serije ne mogu poslužiti kao heterobivalentni ligandi.Preliminarna doking analiza urađena je za jedinjenja koja su pokazala farmakološku aktivnost.
AB  - This PhD thesis encompasses the design of 30 anilidopiperidines, as analogues of potent -opioid agonist and clinical analgesic, fentanyl. All compounds were prepared by the novel and effcient synthetic routes, and can be divided in two series. In the first series, 13 new analogues of fentanyl with various nitrogen groups in the C3 position of the piperidine ring were synthesized. In addition, the synthesis of two bicyclic analogues of fentanyl, previously synthesized by our group, was optimized. The compounds of the first series represent the first known fentanyl analogues possessing any nitrogen substituent at C3 position of the piperidine ring. The second series involved preparation of 15 new compounds consisting of fentanyl moiety and several arylpiperazine groups joined by the respective secondary nitrogens, via the variable-length alkyl linkers. The compounds were designed to be potential heterobivalent ligands, since they include both the fentanyl core, as the -opioid agonist pharmacophore, and N-arylpiperazine moiety as the D2-dopaminergic agonist pharmacophore.The analgesic activity of 30 compounds was tested in vivo. Only four compounds, all from the first series, showed analgesic activity. The most potent of them was 1.8 times less potent analgesic than fentanyl, with fast onset and short duration of analgesic effect, which makes this compound potentially suitable for different pharmacological formulation in the pain treatment. Binding affinity of the compounds of the second series towards dopaminergic D2 receptors was determined by in vitro competitive assay, using 3H spiperon as radioactive ligand. Compounds of the second series were found to be inactive as analgesics and with low affinity towards dopaminergic D2 receptors. Therefore, the compounds do not represent heterobivalent ligands.Preliminary docking analysis was performed for the pharmacologically active compounds.
PB  - Универзитет у Београду, Хемијски факултет
T2  - Универзитет у Београду
T1  - Sinteza, farmakološko ispitivanje i doking analiza novih anilidopiperidina
UR  - https://hdl.handle.net/21.15107/rcub_nardus_17614
ER  - 

@phdthesis{
author = "Jevtić, Ivana",
year = "2020",
abstract = "U okviru ove disertacije dizajnirano je 30 anilidopipredina, analoga jakog -opioidnog agonista i kliničkog analgetika fentanila. Razvijen je efikasan sintetički put za njihovo dobijanje, a sintetisana jedinjenja mogu se podeliti u dve serije. U okviru prve serije sintetisano je 13 novih analoga fentanila sa različitim azotnim grupama u položaju C3 piperidinskog prstena. Takođe je optimizovana sinteza dva prethodno sintetisana biciklična analoga fentanila. Jedinjenja prve serije predstavljaju prve poznate analoge fentanila sa azotnim grupama u položaju C3. U okviru druge serije sintetisano je 15 novih analoga fentanila, koji su u položaju N1 povezani sa pojedinim N-arilpiperazinima preko linearnih alkil mostova različitih dužina. Jedinjenja druge serije dizajnirana su da budu potencijalni heterobivalenti ligandi, jer sadrže anilidopiperidinsko jezgro fentanila kao -opioidnu agonističku farmakoforu, a N-arilpiperazin kao D2-dopaminergičku, agonističku farmakoforu.Analgetička aktivnost svih 30 jedinjenja ispitana je in vivo. Samo četiri jedinjenja, sva iz prve serije, pokazala su analgetičku aktivnost. Najaktivnije jedinjenje, oko 1,8 puta manje aktivno od fentanila, karakterišu brzo i kratko dejstvo analgetičkog efekta, pa se stoga može potencijalno iskoristiti u različitim farmacutskim formulacijama za tretman bola. Afinitet vezivanja jedinjenja druge serije za dopaminergčke D2 receptore ispitan je in vitro testovima kompeticije koristeći 3H spiperon kao radioaktivni ligand. Odsustvo analgetičke aktivnosti i slab afinitet vezivanja za dopaminergičke D2 receptore, ukazuje da jedinjenja druge serije ne mogu poslužiti kao heterobivalentni ligandi.Preliminarna doking analiza urađena je za jedinjenja koja su pokazala farmakološku aktivnost., This PhD thesis encompasses the design of 30 anilidopiperidines, as analogues of potent -opioid agonist and clinical analgesic, fentanyl. All compounds were prepared by the novel and effcient synthetic routes, and can be divided in two series. In the first series, 13 new analogues of fentanyl with various nitrogen groups in the C3 position of the piperidine ring were synthesized. In addition, the synthesis of two bicyclic analogues of fentanyl, previously synthesized by our group, was optimized. The compounds of the first series represent the first known fentanyl analogues possessing any nitrogen substituent at C3 position of the piperidine ring. The second series involved preparation of 15 new compounds consisting of fentanyl moiety and several arylpiperazine groups joined by the respective secondary nitrogens, via the variable-length alkyl linkers. The compounds were designed to be potential heterobivalent ligands, since they include both the fentanyl core, as the -opioid agonist pharmacophore, and N-arylpiperazine moiety as the D2-dopaminergic agonist pharmacophore.The analgesic activity of 30 compounds was tested in vivo. Only four compounds, all from the first series, showed analgesic activity. The most potent of them was 1.8 times less potent analgesic than fentanyl, with fast onset and short duration of analgesic effect, which makes this compound potentially suitable for different pharmacological formulation in the pain treatment. Binding affinity of the compounds of the second series towards dopaminergic D2 receptors was determined by in vitro competitive assay, using 3H spiperon as radioactive ligand. Compounds of the second series were found to be inactive as analgesics and with low affinity towards dopaminergic D2 receptors. Therefore, the compounds do not represent heterobivalent ligands.Preliminary docking analysis was performed for the pharmacologically active compounds.",
publisher = "Универзитет у Београду, Хемијски факултет",
journal = "Универзитет у Београду",
title = "Sinteza, farmakološko ispitivanje i doking analiza novih anilidopiperidina",
url = "https://hdl.handle.net/21.15107/rcub_nardus_17614"
}

Jevtić, I.. (2020). Sinteza, farmakološko ispitivanje i doking analiza novih anilidopiperidina. in Универзитет у Београду
Универзитет у Београду, Хемијски факултет..
https://hdl.handle.net/21.15107/rcub_nardus_17614

Jevtić I. Sinteza, farmakološko ispitivanje i doking analiza novih anilidopiperidina. in Универзитет у Београду. 2020;.
https://hdl.handle.net/21.15107/rcub_nardus_17614 .

Jevtić, Ivana, "Sinteza, farmakološko ispitivanje i doking analiza novih anilidopiperidina" in Универзитет у Београду (2020),
https://hdl.handle.net/21.15107/rcub_nardus_17614 .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Savić-Vujović, Katarina
AU  - Srebro, Dragana
AU  - Vučković, Sonja
AU  - Ivanović, Milovan
AU  - Kostić Rajačić, Slađana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3999
AB  - Herein, the synthesis and pharmacological evaluation of 13 novel compounds, designed as potential heterobivalent ligands for μ-opioid receptor (MOR) and dopamine D2 receptors (D2DAR), are reported. The compounds consisted of anilido piperidine and N-aryl piperazine moieties, joined by a variable-length methylene linker. The two moieties represent MOR and D2DAR pharmacophores, respectively. The synthesis encompassed four steps, securing the final products in 28–42 % overall yields. The approach has a considerable synthetic potential, providing access to various related structures. Pharmacological tests involved in vitro competitive assay for D2DAR using [3H] spiperon, as a standard radioligand, and in vivo antinociceptive tests for MOR. The measured dopamine affinities were modest to low, while antinociceptive activity was completely absent. Therefore, the compounds of the general structure prepared in this research are unlikely to be useful as opioid–dopamine receptor heterobivalent ligands.
AB  - У овом раду је приказана синтеза и фармаколошко испитивање 13 нових једињења, дизајнираних са циљем да буду потенцијални бивалентни лиганди за μ-опиоидни рецептор (MOR) и допамински D2 рецептор (D2DAR). Једињења се састоје од анилидо-пиперидинских (МОR фармакофора) и N-арилпиперазинских остатака (D2DAR фармакофора), повезаних метиленским ланцем променљиве дужине. Синтеза је обухватала четири корака, обезбеђујући крајње производе у укупним приносима од 28 до 42 %. Афинитет везивања за D2DAR одређен је in vitro тестом компетиције користећи [3H] спиперон као стандардни радиолиганд док је антиноцицептивна (опиоидна) активност испитана in vivo
антиноцицептивним тестом. Активности новосинтетисаних једињења ка D2DAR биле су умерене до ниске, док је антиноцицептивна активност у потпуности изостала.
PB  - Belgrade : Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation
T1  - Ligandi koji sadrže farmakofore za μ-opioidne i D2 dopaminske receptore: Sinteza i farmakološko ispitivanje
VL  - 85
IS  - 6
SP  - 711
EP  - 720
DO  - 10.2298/JSC190912118J
ER  - 

@article{
author = "Jevtić, Ivana and Penjišević, Jelena and Savić-Vujović, Katarina and Srebro, Dragana and Vučković, Sonja and Ivanović, Milovan and Kostić Rajačić, Slađana",
year = "2020",
abstract = "Herein, the synthesis and pharmacological evaluation of 13 novel compounds, designed as potential heterobivalent ligands for μ-opioid receptor (MOR) and dopamine D2 receptors (D2DAR), are reported. The compounds consisted of anilido piperidine and N-aryl piperazine moieties, joined by a variable-length methylene linker. The two moieties represent MOR and D2DAR pharmacophores, respectively. The synthesis encompassed four steps, securing the final products in 28–42 % overall yields. The approach has a considerable synthetic potential, providing access to various related structures. Pharmacological tests involved in vitro competitive assay for D2DAR using [3H] spiperon, as a standard radioligand, and in vivo antinociceptive tests for MOR. The measured dopamine affinities were modest to low, while antinociceptive activity was completely absent. Therefore, the compounds of the general structure prepared in this research are unlikely to be useful as opioid–dopamine receptor heterobivalent ligands., У овом раду је приказана синтеза и фармаколошко испитивање 13 нових једињења, дизајнираних са циљем да буду потенцијални бивалентни лиганди за μ-опиоидни рецептор (MOR) и допамински D2 рецептор (D2DAR). Једињења се састоје од анилидо-пиперидинских (МОR фармакофора) и N-арилпиперазинских остатака (D2DAR фармакофора), повезаних метиленским ланцем променљиве дужине. Синтеза је обухватала четири корака, обезбеђујући крајње производе у укупним приносима од 28 до 42 %. Афинитет везивања за D2DAR одређен је in vitro тестом компетиције користећи [3H] спиперон као стандардни радиолиганд док је антиноцицептивна (опиоидна) активност испитана in vivo
антиноцицептивним тестом. Активности новосинтетисаних једињења ка D2DAR биле су умерене до ниске, док је антиноцицептивна активност у потпуности изостала.",
publisher = "Belgrade : Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation, Ligandi koji sadrže farmakofore za μ-opioidne i D2 dopaminske receptore: Sinteza i farmakološko ispitivanje",
volume = "85",
number = "6",
pages = "711-720",
doi = "10.2298/JSC190912118J"
}

Jevtić, I., Penjišević, J., Savić-Vujović, K., Srebro, D., Vučković, S., Ivanović, M.,& Kostić Rajačić, S.. (2020). μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society
Belgrade : Serbian Chemical Society., 85(6), 711-720.
https://doi.org/10.2298/JSC190912118J

Jevtić I, Penjišević J, Savić-Vujović K, Srebro D, Vučković S, Ivanović M, Kostić Rajačić S. μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation. in Journal of the Serbian Chemical Society. 2020;85(6):711-720.
doi:10.2298/JSC190912118J .

Jevtić, Ivana, Penjišević, Jelena, Savić-Vujović, Katarina, Srebro, Dragana, Vučković, Sonja, Ivanović, Milovan, Kostić Rajačić, Slađana, "μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation" in Journal of the Serbian Chemical Society, 85, no. 6 (2020):711-720,
https://doi.org/10.2298/JSC190912118J . .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Lai, Thu Hang
AU  - Penjišević, Jelena
AU  - Dukić-Stefanović, Sladjana
AU  - Andrić, Deana
AU  - Brust, Peter
AU  - Kostić Rajačić, Slađana
AU  - Teodoro, Rodrigo
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4040
AB  - Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.
PB  - MDPI
T2  - Molecules
T1  - Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding
VL  - 25
IS  - 21
SP  - 4941
DO  - 10.3390/molecules25214941
ER  - 

@article{
author = "Jevtić, Ivana and Lai, Thu Hang and Penjišević, Jelena and Dukić-Stefanović, Sladjana and Andrić, Deana and Brust, Peter and Kostić Rajačić, Slađana and Teodoro, Rodrigo",
year = "2020",
abstract = "Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 8–17 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 8–17 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands.",
publisher = "MDPI",
journal = "Molecules",
title = "Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding",
volume = "25",
number = "21",
pages = "4941",
doi = "10.3390/molecules25214941"
}

Jevtić, I., Lai, T. H., Penjišević, J., Dukić-Stefanović, S., Andrić, D., Brust, P., Kostić Rajačić, S.,& Teodoro, R.. (2020). Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding. in Molecules
MDPI., 25(21), 4941.
https://doi.org/10.3390/molecules25214941

Jevtić I, Lai TH, Penjišević J, Dukić-Stefanović S, Andrić D, Brust P, Kostić Rajačić S, Teodoro R. Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding. in Molecules. 2020;25(21):4941.
doi:10.3390/molecules25214941 .

Jevtić, Ivana, Lai, Thu Hang, Penjišević, Jelena, Dukić-Stefanović, Sladjana, Andrić, Deana, Brust, Peter, Kostić Rajačić, Slađana, Teodoro, Rodrigo, "Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding" in Molecules, 25, no. 21 (2020):4941,
https://doi.org/10.3390/molecules25214941 . .

TY  - CONF
AU  - Jevtić, Ivana
AU  - Lai, Hang
AU  - Penjišević, Jelena
AU  - Teodoro, Rodrigo
AU  - Dukic-Stefanovic, Sladjana
AU  - Brust, Peter
AU  - Kostić-Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5836
AB  - The aim of this study was to develop highly specific radiofluorinated ligands for quantitative positron emission tomography (PET) imaging of monoamine oxidase-B (MAO-B) in brain. A series of 8 fluoro derivatives of 1-cinnamyl-4-arylpiperazine were synthesized by standard methods of organic synthesis. The affinity of the compounds was determined in a competitive binding assay using L-[3H] deprenyl as radioligand on rat brain homogenates. The KD of the radioligand was determined by homologous competition. An efficient, three-step procedure for the synthesis of the potential MAO-B ligands was developed. A competitive binding assay was established, using L-[3H]deprenyl as the radioligand, and rat brain membrane homogenate. The compounds were screened (three concentrations 10-9, 10-7 and 10-5) for their MAO-B affinity. We successfully synthesized a series of fluorinated MAO-B ligands. Unfortunately, their affinities toward MAO-B have proved to be rather low. To increase the affinity further modifications are needed.
PB  - Serbian Neuroscience Society / Društvo za neuronauke Srbije
PB  - National Neurocience Society of Romania
PB  - Neuroscience Society of Turkey
C3  - Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia
T1  - Synthesis and biological evaluation of new, potential MAO-B ligands.
SP  - 286
EP  - 286
UR  - https://hdl.handle.net/21.15107/rcub_cer_5836
ER  - 

@conference{
author = "Jevtić, Ivana and Lai, Hang and Penjišević, Jelena and Teodoro, Rodrigo and Dukic-Stefanovic, Sladjana and Brust, Peter and Kostić-Rajačić, Slađana",
year = "2019",
abstract = "The aim of this study was to develop highly specific radiofluorinated ligands for quantitative positron emission tomography (PET) imaging of monoamine oxidase-B (MAO-B) in brain. A series of 8 fluoro derivatives of 1-cinnamyl-4-arylpiperazine were synthesized by standard methods of organic synthesis. The affinity of the compounds was determined in a competitive binding assay using L-[3H] deprenyl as radioligand on rat brain homogenates. The KD of the radioligand was determined by homologous competition. An efficient, three-step procedure for the synthesis of the potential MAO-B ligands was developed. A competitive binding assay was established, using L-[3H]deprenyl as the radioligand, and rat brain membrane homogenate. The compounds were screened (three concentrations 10-9, 10-7 and 10-5) for their MAO-B affinity. We successfully synthesized a series of fluorinated MAO-B ligands. Unfortunately, their affinities toward MAO-B have proved to be rather low. To increase the affinity further modifications are needed.",
publisher = "Serbian Neuroscience Society / Društvo za neuronauke Srbije, National Neurocience Society of Romania, Neuroscience Society of Turkey",
journal = "Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia",
title = "Synthesis and biological evaluation of new, potential MAO-B ligands.",
pages = "286-286",
url = "https://hdl.handle.net/21.15107/rcub_cer_5836"
}

Jevtić, I., Lai, H., Penjišević, J., Teodoro, R., Dukic-Stefanovic, S., Brust, P.,& Kostić-Rajačić, S.. (2019). Synthesis and biological evaluation of new, potential MAO-B ligands.. in Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia
Serbian Neuroscience Society / Društvo za neuronauke Srbije., 286-286.
https://hdl.handle.net/21.15107/rcub_cer_5836

Jevtić I, Lai H, Penjišević J, Teodoro R, Dukic-Stefanovic S, Brust P, Kostić-Rajačić S. Synthesis and biological evaluation of new, potential MAO-B ligands.. in Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia. 2019;:286-286.
https://hdl.handle.net/21.15107/rcub_cer_5836 .

Jevtić, Ivana, Lai, Hang, Penjišević, Jelena, Teodoro, Rodrigo, Dukic-Stefanovic, Sladjana, Brust, Peter, Kostić-Rajačić, Slađana, "Synthesis and biological evaluation of new, potential MAO-B ligands." in Abstract Book - FENS regional meeting, July 10-13, 2019, Belgrade, Serbia (2019):286-286,
https://hdl.handle.net/21.15107/rcub_cer_5836 .

TY  - JOUR
AU  - Jevtić, Ivana
AU  - Penjišević, Jelena
AU  - Ivanović, Milovan D.
AU  - Kostić Rajačić, Slađana
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3249
AB  - A scalable, cost-efficient and simple synthetic pathway towards potential bivalent opioid/dopamine receptor ligands was developed and optimized. Three novel compounds that contain both opioid and dopamine pharmacophores linked by the four methylene group chain were synthesized in 33, 35 and 39 % overall yield after a four-step synthetic route starting from three commercially available N-aryl piperazines. The anilino piperidine precursor was easily prepared in three steps, as previously published, starting from 4- piperidone. The synthesis presented in this paper could be of interest for heterocyclic and general organic chemistry. The newly designed compounds possessing two pharmacophores, opioid and D2/D3, are potentially useful pharmacological probes. Of particular interest would be the simultaneous binding to both opioid and D2/D3 receptors, and the resulting pharmacological responses may be useful for the further understanding of tolerance and dependence phenomena in opioid clinical use and/or abuse.
AB  - Три нова једињења, која садрже опиоидну и допаминску фармакофору, спојене преко четири метиленске групе, синтетисанa су у четири фазе у укупном приносу од приближно 35 %, полазећи од три комерцијално доступна N-арилпиперазина. Анилино- пиперидински прекурсор је добијен у три једноставне реакционе фазе, полазећи од 4-пиперидона, према познатој литературној методи. Синтеза приказана у овом раду може бити од значаја за хетероцикличну и органску хемију у целини. Новосинтетисана једињења која поседују две фармакофоре, опиоидну и Д2/Д3, су потенцијално корисни супстрати за фармаколошка испитивања. Од посебног интереса може бити истовремено везивање за опиоидне и Д2/Д3 рецепторе, а резултујући фармаколошки одговор био би користан у даљем разумевању толеранције и зависности, као феномена везаних за кли- ничку употребу и/или злоупотребу опијата.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores
T1  - Синтетички пут за синтезу потенцијалних, бивалентних лиганада који поседују опоидну и допамин Д2/Д3 фармакогфору
VL  - 84
IS  - 7
SP  - 639
EP  - 647
DO  - 10.2298/JSC181002105J
ER  - 

@article{
author = "Jevtić, Ivana and Penjišević, Jelena and Ivanović, Milovan D. and Kostić Rajačić, Slađana",
year = "2019",
abstract = "A scalable, cost-efficient and simple synthetic pathway towards potential bivalent opioid/dopamine receptor ligands was developed and optimized. Three novel compounds that contain both opioid and dopamine pharmacophores linked by the four methylene group chain were synthesized in 33, 35 and 39 % overall yield after a four-step synthetic route starting from three commercially available N-aryl piperazines. The anilino piperidine precursor was easily prepared in three steps, as previously published, starting from 4- piperidone. The synthesis presented in this paper could be of interest for heterocyclic and general organic chemistry. The newly designed compounds possessing two pharmacophores, opioid and D2/D3, are potentially useful pharmacological probes. Of particular interest would be the simultaneous binding to both opioid and D2/D3 receptors, and the resulting pharmacological responses may be useful for the further understanding of tolerance and dependence phenomena in opioid clinical use and/or abuse., Три нова једињења, која садрже опиоидну и допаминску фармакофору, спојене преко четири метиленске групе, синтетисанa су у четири фазе у укупном приносу од приближно 35 %, полазећи од три комерцијално доступна N-арилпиперазина. Анилино- пиперидински прекурсор је добијен у три једноставне реакционе фазе, полазећи од 4-пиперидона, према познатој литературној методи. Синтеза приказана у овом раду може бити од значаја за хетероцикличну и органску хемију у целини. Новосинтетисана једињења која поседују две фармакофоре, опиоидну и Д2/Д3, су потенцијално корисни супстрати за фармаколошка испитивања. Од посебног интереса може бити истовремено везивање за опиоидне и Д2/Д3 рецепторе, а резултујући фармаколошки одговор био би користан у даљем разумевању толеранције и зависности, као феномена везаних за кли- ничку употребу и/или злоупотребу опијата.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores, Синтетички пут за синтезу потенцијалних, бивалентних лиганада који поседују опоидну и допамин Д2/Д3 фармакогфору",
volume = "84",
number = "7",
pages = "639-647",
doi = "10.2298/JSC181002105J"
}

Jevtić, I., Penjišević, J., Ivanović, M. D.,& Kostić Rajačić, S.. (2019). Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 84(7), 639-647.
https://doi.org/10.2298/JSC181002105J

Jevtić I, Penjišević J, Ivanović MD, Kostić Rajačić S. Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores. in Journal of the Serbian Chemical Society. 2019;84(7):639-647.
doi:10.2298/JSC181002105J .

Jevtić, Ivana, Penjišević, Jelena, Ivanović, Milovan D., Kostić Rajačić, Slađana, "Synthetic route towards potential bivalent ligands possessing opioid and D2/D3 pharmacophores" in Journal of the Serbian Chemical Society, 84, no. 7 (2019):639-647,
https://doi.org/10.2298/JSC181002105J . .

TY  - JOUR
AU  - Popović-Đorđević, Jelena B.
AU  - Jevtić, Ivana
AU  - Stanojković, Tatjana
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2315
AB  - Background: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability. Methods: A systematic search of peer-reviewed scientific literature and public databases has been conducted. We included the most recent relevant research papers and data in respect to the focus of the present review. The quality of retrieved papers was assessed using standard tools. Results: The review highlights the chemical structural diversity of the molecules that have the common target-DMT2. So-called traditional antidiabetics as well as the newest and the least explored drugs include polypeptides and amino acid derivatives (insulin, glucagon-like peptide 1, dipeptidyl peptidase-IV inhibitors, amylin), sulfonylurea derivatives, benzylthiazolidine-2,4-diones (peroxisome proliferator activated receptor-gamma agonists/glitazones), condensed guanido core (metformin) and sugar-like molecules (alpha-glucosidase and sodium/glucose co-transporter 2 inhibitors). Conclusion: As diabetes becomes a more common disease, interest in new pharmacological targets is on the rise.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Medicinal Chemistry
T1  - Antidiabetics: Structural Diversity of Molecules with a Common Aim
VL  - 25
IS  - 18
SP  - 2140
EP  - 2165
DO  - 10.2174/0929867325666171205145309
ER  - 

@article{
author = "Popović-Đorđević, Jelena B. and Jevtić, Ivana and Stanojković, Tatjana",
year = "2018",
abstract = "Background: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability. Methods: A systematic search of peer-reviewed scientific literature and public databases has been conducted. We included the most recent relevant research papers and data in respect to the focus of the present review. The quality of retrieved papers was assessed using standard tools. Results: The review highlights the chemical structural diversity of the molecules that have the common target-DMT2. So-called traditional antidiabetics as well as the newest and the least explored drugs include polypeptides and amino acid derivatives (insulin, glucagon-like peptide 1, dipeptidyl peptidase-IV inhibitors, amylin), sulfonylurea derivatives, benzylthiazolidine-2,4-diones (peroxisome proliferator activated receptor-gamma agonists/glitazones), condensed guanido core (metformin) and sugar-like molecules (alpha-glucosidase and sodium/glucose co-transporter 2 inhibitors). Conclusion: As diabetes becomes a more common disease, interest in new pharmacological targets is on the rise.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Medicinal Chemistry",
title = "Antidiabetics: Structural Diversity of Molecules with a Common Aim",
volume = "25",
number = "18",
pages = "2140-2165",
doi = "10.2174/0929867325666171205145309"
}

Popović-Đorđević, J. B., Jevtić, I.,& Stanojković, T.. (2018). Antidiabetics: Structural Diversity of Molecules with a Common Aim. in Current Medicinal Chemistry
Bentham Science Publ Ltd, Sharjah., 25(18), 2140-2165.
https://doi.org/10.2174/0929867325666171205145309

Popović-Đorđević JB, Jevtić I, Stanojković T. Antidiabetics: Structural Diversity of Molecules with a Common Aim. in Current Medicinal Chemistry. 2018;25(18):2140-2165.
doi:10.2174/0929867325666171205145309 .

Popović-Đorđević, Jelena B., Jevtić, Ivana, Stanojković, Tatjana, "Antidiabetics: Structural Diversity of Molecules with a Common Aim" in Current Medicinal Chemistry, 25, no. 18 (2018):2140-2165,
https://doi.org/10.2174/0929867325666171205145309 . .

TY  - JOUR
AU  - Popović-Đorđević, Jelena B.
AU  - Jevtić, Ivana
AU  - Grozdanic, Nadja Dj
AU  - Šegan, Sandra
AU  - Zlatović, Mario
AU  - Ivanović, Milovan D.
AU  - Stanojković, Tatjana
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2063
AB  - The inhibitory activities of selected cyclic urea and carbamate derivatives (1-13) toward alpha-glucosidase (alpha-Gls) in in vitro assay were examined in this study. All examined compounds showed higher inhibitory activity (IC50) against alpha-Gls compared to standard antidiabetic drug acarbose. The most potent was benzyl (3,4,5-trimethoxyphenyl) carbamate (12) with IC50 = 49.85 +/- 0.10 mu M. In vitro cytotoxicity of the investigated compounds was tested on three human cancer cell lines HeLa, A549 and MDA-MB-453 using MTT assay. The best antitumour activity was achieved with compound 2 (trans-5-phenethyl-1-phenylhexahydro-1H-imidazo[4,5-c] pyridin-2(3H)-one) against MDA-MB-453 human breast cancer cell line (IC50 = 83.41 +/- 1.60 mu M). Cyclic ureas and carbamates showed promising anti-alpha-glucosidase activity and should be further tested as potential antidiabetic drugs. The PLS model of preliminary QSAR study indicated that, in planing the future synthesis of more potent compounds, the newly designed should have the substituents capable of polar interactions with receptor sites in various positions, while avoiding the increase of their lipophilicity.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Journal of Enzyme Inhibition and Medicinal Chemistry
T1  - alpha-Glucosidase inhibitory activity and cytotoxic effects of some cyclic urea and carbamate derivatives
VL  - 32
IS  - 1
SP  - 298
EP  - 303
DO  - 10.1080/14756366.2016.1250754
ER  - 

@article{
author = "Popović-Đorđević, Jelena B. and Jevtić, Ivana and Grozdanic, Nadja Dj and Šegan, Sandra and Zlatović, Mario and Ivanović, Milovan D. and Stanojković, Tatjana",
year = "2017",
abstract = "The inhibitory activities of selected cyclic urea and carbamate derivatives (1-13) toward alpha-glucosidase (alpha-Gls) in in vitro assay were examined in this study. All examined compounds showed higher inhibitory activity (IC50) against alpha-Gls compared to standard antidiabetic drug acarbose. The most potent was benzyl (3,4,5-trimethoxyphenyl) carbamate (12) with IC50 = 49.85 +/- 0.10 mu M. In vitro cytotoxicity of the investigated compounds was tested on three human cancer cell lines HeLa, A549 and MDA-MB-453 using MTT assay. The best antitumour activity was achieved with compound 2 (trans-5-phenethyl-1-phenylhexahydro-1H-imidazo[4,5-c] pyridin-2(3H)-one) against MDA-MB-453 human breast cancer cell line (IC50 = 83.41 +/- 1.60 mu M). Cyclic ureas and carbamates showed promising anti-alpha-glucosidase activity and should be further tested as potential antidiabetic drugs. The PLS model of preliminary QSAR study indicated that, in planing the future synthesis of more potent compounds, the newly designed should have the substituents capable of polar interactions with receptor sites in various positions, while avoiding the increase of their lipophilicity.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
title = "alpha-Glucosidase inhibitory activity and cytotoxic effects of some cyclic urea and carbamate derivatives",
volume = "32",
number = "1",
pages = "298-303",
doi = "10.1080/14756366.2016.1250754"
}

Popović-Đorđević, J. B., Jevtić, I., Grozdanic, N. D., Šegan, S., Zlatović, M., Ivanović, M. D.,& Stanojković, T.. (2017). alpha-Glucosidase inhibitory activity and cytotoxic effects of some cyclic urea and carbamate derivatives. in Journal of Enzyme Inhibition and Medicinal Chemistry
Taylor & Francis Ltd, Abingdon., 32(1), 298-303.
https://doi.org/10.1080/14756366.2016.1250754

Popović-Đorđević JB, Jevtić I, Grozdanic ND, Šegan S, Zlatović M, Ivanović MD, Stanojković T. alpha-Glucosidase inhibitory activity and cytotoxic effects of some cyclic urea and carbamate derivatives. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2017;32(1):298-303.
doi:10.1080/14756366.2016.1250754 .

Popović-Đorđević, Jelena B., Jevtić, Ivana, Grozdanic, Nadja Dj, Šegan, Sandra, Zlatović, Mario, Ivanović, Milovan D., Stanojković, Tatjana, "alpha-Glucosidase inhibitory activity and cytotoxic effects of some cyclic urea and carbamate derivatives" in Journal of Enzyme Inhibition and Medicinal Chemistry, 32, no. 1 (2017):298-303,
https://doi.org/10.1080/14756366.2016.1250754 . .

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 . .