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  - 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  - Jovanovic, Jovana
AU  - Kolarevic, Stoimir
AU  - Miloskovic, Aleksandra
AU  - Radojkovic, Natasa
AU  - Simić, Vladica
AU  - Dojčinović, Biljana
AU  - Kracun-Kolarevic, Margareta
AU  - Paunović, Momir
AU  - Kostic, Jovana
AU  - Sunjog, Karolina
AU  - Timilijic, Jovana
AU  - Đorđević, Jelena B.
AU  - Gačić, Zoran
AU  - Zegura, Bojana
AU  - Vukovic-Gacic, Branka
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2468
AB  - The Velika Morava River is the greatest national Serbian river and the significant tributary of the Danube River. The major problems in the Velika Morava River Basin (VMRB) represent untreated industrial and municipal wastewaters. In this study, the level of genotoxic potential at the sites along the VMRB was evaluated by parallel in vitro and in situ approach. Within in vitro testing, genotoxicity of native water samples collected from the sites in VMRB was evaluated by SOS/umuC test on Salmonella typhimurium TA1535/pSK1002 and by the comet assay on HepG2 cells. DNA damage in situ was assessed in bleak (Alburnus alburnus) erythrocytes by the comet (alkaline and Fpg-modified comet) and micronucleus assays. Additionally, the concentration of heavy metals in fish tissue was measured and this data, compiled with the data of the physico-chemical parameters measured in water, was used as a measure of the pollution pressure at the sites. Results showed that applied in vitro tests with native water samples are less sensitive in comparison with in situ tests and should be taken with precaution when making predictions on the status of the ecosystem. Within applied battery of in situ assays differential sensitivity of assays was observed where alkaline comet assay showed the highest potential in differentiation of the sites based on genotoxic potential. Integrated biomarker response showed that usage of the battery of bioassays provides better insight in a genotoxic effects in animals, and consequently, that the holistic approach is more suitable for this type of study.
PB  - Elsevier
T2  - Science of the Total Environment
T1  - Evaluation of genotoxic potential in the Velika Morava River Basin in vitro and in situ
VL  - 621
SP  - 1289
EP  - 1299
DO  - 10.1016/j.scitotenv.2017.10.099
ER  - 

@article{
author = "Jovanovic, Jovana and Kolarevic, Stoimir and Miloskovic, Aleksandra and Radojkovic, Natasa and Simić, Vladica and Dojčinović, Biljana and Kracun-Kolarevic, Margareta and Paunović, Momir and Kostic, Jovana and Sunjog, Karolina and Timilijic, Jovana and Đorđević, Jelena B. and Gačić, Zoran and Zegura, Bojana and Vukovic-Gacic, Branka",
year = "2018",
abstract = "The Velika Morava River is the greatest national Serbian river and the significant tributary of the Danube River. The major problems in the Velika Morava River Basin (VMRB) represent untreated industrial and municipal wastewaters. In this study, the level of genotoxic potential at the sites along the VMRB was evaluated by parallel in vitro and in situ approach. Within in vitro testing, genotoxicity of native water samples collected from the sites in VMRB was evaluated by SOS/umuC test on Salmonella typhimurium TA1535/pSK1002 and by the comet assay on HepG2 cells. DNA damage in situ was assessed in bleak (Alburnus alburnus) erythrocytes by the comet (alkaline and Fpg-modified comet) and micronucleus assays. Additionally, the concentration of heavy metals in fish tissue was measured and this data, compiled with the data of the physico-chemical parameters measured in water, was used as a measure of the pollution pressure at the sites. Results showed that applied in vitro tests with native water samples are less sensitive in comparison with in situ tests and should be taken with precaution when making predictions on the status of the ecosystem. Within applied battery of in situ assays differential sensitivity of assays was observed where alkaline comet assay showed the highest potential in differentiation of the sites based on genotoxic potential. Integrated biomarker response showed that usage of the battery of bioassays provides better insight in a genotoxic effects in animals, and consequently, that the holistic approach is more suitable for this type of study.",
publisher = "Elsevier",
journal = "Science of the Total Environment",
title = "Evaluation of genotoxic potential in the Velika Morava River Basin in vitro and in situ",
volume = "621",
pages = "1289-1299",
doi = "10.1016/j.scitotenv.2017.10.099"
}

Jovanovic, J., Kolarevic, S., Miloskovic, A., Radojkovic, N., Simić, V., Dojčinović, B., Kracun-Kolarevic, M., Paunović, M., Kostic, J., Sunjog, K., Timilijic, J., Đorđević, J. B., Gačić, Z., Zegura, B.,& Vukovic-Gacic, B.. (2018). Evaluation of genotoxic potential in the Velika Morava River Basin in vitro and in situ. in Science of the Total Environment
Elsevier., 621, 1289-1299.
https://doi.org/10.1016/j.scitotenv.2017.10.099

Jovanovic J, Kolarevic S, Miloskovic A, Radojkovic N, Simić V, Dojčinović B, Kracun-Kolarevic M, Paunović M, Kostic J, Sunjog K, Timilijic J, Đorđević JB, Gačić Z, Zegura B, Vukovic-Gacic B. Evaluation of genotoxic potential in the Velika Morava River Basin in vitro and in situ. in Science of the Total Environment. 2018;621:1289-1299.
doi:10.1016/j.scitotenv.2017.10.099 .

Jovanovic, Jovana, Kolarevic, Stoimir, Miloskovic, Aleksandra, Radojkovic, Natasa, Simić, Vladica, Dojčinović, Biljana, Kracun-Kolarevic, Margareta, Paunović, Momir, Kostic, Jovana, Sunjog, Karolina, Timilijic, Jovana, Đorđević, Jelena B., Gačić, Zoran, Zegura, Bojana, Vukovic-Gacic, Branka, "Evaluation of genotoxic potential in the Velika Morava River Basin in vitro and in situ" in Science of the Total Environment, 621 (2018):1289-1299,
https://doi.org/10.1016/j.scitotenv.2017.10.099 . .

TY  - CONF
AU  - Marković, Goran
AU  - Popović - Đorđević, Jelena
AU  - Pantelić, Nebojša
AU  - Dojčinović, Biljana
AU  - Kostić, Aleksandar Ž.
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6432
AB  - Water is one of the most precious natural resources. The downtrend in the quality of lake water and pollution with heavy metals cause serious threats to the environment in last decades. Particularly vulnerable are the lakes that are located near towns and villages. The aim of this study was to investigate the physicochemical parameters and levels of macro– and microelements in order to determine the water quality of Lake Gruža in the summer period. The results showed that the studied parameters were within the permissible levels, except of concentrations of iron, cobalt and vanadium.
AB  - Voda predstavlja jedan od najdragocenijih prirodnih resursa. Opadanje kvaliteta jezerskih voda i zagađenje teškim metalima, predstavljaju ozbiljne pretnje za životnu sredinu u poslednjih nekoliko decenija. Posebno su ugrožena jezera koja se nalaze u blizini gradova i naselja. Cilj rada bio je ispitivanje osnovnih fizičko–hemijskih parametara i sadržaja makro– i mikroelemenata kako bi se utvrdio kvalitet vode jezera Gruža u letnjem periodu. Rezultati su pokazali da su ispitivani parametri u vodi bili u okviru dozvoljenih vrednosti, osim sadržaja gvožđa, kobalta i vanadijuma.
PB  - Čačak : Univerzitet u Kragujevcu, Agronomski fakultet
C3  - Zbornik radova - 22. Savetovanje o biotehnologiji sa međunarodnim učešćem,  10.-11. 03. 2017, Čačak, Srbija
T1  - Study of Selected Physicochemical Characteristics and Content of Macro– And Microelements in the Lake Gruža Water
T1  - Ispitivanje odabranih fizičko–hemijskih osobina i sadržaja makro- i mikroelemenata u vodi jezera Gruža
SP  - 297
EP  - 301
UR  - https://hdl.handle.net/21.15107/rcub_cer_6432
ER  - 

@conference{
author = "Marković, Goran and Popović - Đorđević, Jelena and Pantelić, Nebojša and Dojčinović, Biljana and Kostić, Aleksandar Ž.",
year = "2017",
abstract = "Water is one of the most precious natural resources. The downtrend in the quality of lake water and pollution with heavy metals cause serious threats to the environment in last decades. Particularly vulnerable are the lakes that are located near towns and villages. The aim of this study was to investigate the physicochemical parameters and levels of macro– and microelements in order to determine the water quality of Lake Gruža in the summer period. The results showed that the studied parameters were within the permissible levels, except of concentrations of iron, cobalt and vanadium., Voda predstavlja jedan od najdragocenijih prirodnih resursa. Opadanje kvaliteta jezerskih voda i zagađenje teškim metalima, predstavljaju ozbiljne pretnje za životnu sredinu u poslednjih nekoliko decenija. Posebno su ugrožena jezera koja se nalaze u blizini gradova i naselja. Cilj rada bio je ispitivanje osnovnih fizičko–hemijskih parametara i sadržaja makro– i mikroelemenata kako bi se utvrdio kvalitet vode jezera Gruža u letnjem periodu. Rezultati su pokazali da su ispitivani parametri u vodi bili u okviru dozvoljenih vrednosti, osim sadržaja gvožđa, kobalta i vanadijuma.",
publisher = "Čačak : Univerzitet u Kragujevcu, Agronomski fakultet",
journal = "Zbornik radova - 22. Savetovanje o biotehnologiji sa međunarodnim učešćem,  10.-11. 03. 2017, Čačak, Srbija",
title = "Study of Selected Physicochemical Characteristics and Content of Macro– And Microelements in the Lake Gruža Water, Ispitivanje odabranih fizičko–hemijskih osobina i sadržaja makro- i mikroelemenata u vodi jezera Gruža",
pages = "297-301",
url = "https://hdl.handle.net/21.15107/rcub_cer_6432"
}

Marković, G., Popović - Đorđević, J., Pantelić, N., Dojčinović, B.,& Kostić, A. Ž.. (2017). Study of Selected Physicochemical Characteristics and Content of Macro– And Microelements in the Lake Gruža Water. in Zbornik radova - 22. Savetovanje o biotehnologiji sa međunarodnim učešćem,  10.-11. 03. 2017, Čačak, Srbija
Čačak : Univerzitet u Kragujevcu, Agronomski fakultet., 297-301.
https://hdl.handle.net/21.15107/rcub_cer_6432

Marković G, Popović - Đorđević J, Pantelić N, Dojčinović B, Kostić AŽ. Study of Selected Physicochemical Characteristics and Content of Macro– And Microelements in the Lake Gruža Water. in Zbornik radova - 22. Savetovanje o biotehnologiji sa međunarodnim učešćem,  10.-11. 03. 2017, Čačak, Srbija. 2017;:297-301.
https://hdl.handle.net/21.15107/rcub_cer_6432 .

Marković, Goran, Popović - Đorđević, Jelena, Pantelić, Nebojša, Dojčinović, Biljana, Kostić, Aleksandar Ž., "Study of Selected Physicochemical Characteristics and Content of Macro– And Microelements in the Lake Gruža Water" in Zbornik radova - 22. Savetovanje o biotehnologiji sa međunarodnim učešćem,  10.-11. 03. 2017, Čačak, Srbija (2017):297-301,
https://hdl.handle.net/21.15107/rcub_cer_6432 .

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  - Vitnik, Željko
AU  - Popović-Đorđević, Jelena B.
AU  - Vitnik, Vesna
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2221
AB  - The establishment of the most stable structures of 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione, potential anticancer and antimicrobial drug has been investigated in this work. A detailed interpretation of experimental and calculated IR, UV and NMR spectra were reported. The equilibrium geometry, harmonic vibrational frequencies and electronic properties have been investigated with Density Functional Theory using B3LYP/6-311++G(d,p) method. The scaled theoretical wavenumber showed very good agreement with the experimental values. The charge transfer in the molecule was confirmed with NBO analysis. Ultraviolet-visible spectrum was calculated using TD-DFT method and compared with experimental spectrum. The calculated energy and oscillator strength well reproduce the experimental data. The molecular electrostatic potential surface map portrays potential binding sites of the title molecule.
PB  - Elsevier
T2  - Journal of Molecular Structure
T1  - Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione
VL  - 1137
SP  - 97
EP  - 108
DO  - 10.1016/j.molstruc.2017.02.012
ER  - 

@article{
author = "Vitnik, Željko and Popović-Đorđević, Jelena B. and Vitnik, Vesna",
year = "2017",
abstract = "The establishment of the most stable structures of 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione, potential anticancer and antimicrobial drug has been investigated in this work. A detailed interpretation of experimental and calculated IR, UV and NMR spectra were reported. The equilibrium geometry, harmonic vibrational frequencies and electronic properties have been investigated with Density Functional Theory using B3LYP/6-311++G(d,p) method. The scaled theoretical wavenumber showed very good agreement with the experimental values. The charge transfer in the molecule was confirmed with NBO analysis. Ultraviolet-visible spectrum was calculated using TD-DFT method and compared with experimental spectrum. The calculated energy and oscillator strength well reproduce the experimental data. The molecular electrostatic potential surface map portrays potential binding sites of the title molecule.",
publisher = "Elsevier",
journal = "Journal of Molecular Structure",
title = "Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione",
volume = "1137",
pages = "97-108",
doi = "10.1016/j.molstruc.2017.02.012"
}

Vitnik, Ž., Popović-Đorđević, J. B.,& Vitnik, V.. (2017). Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione. in Journal of Molecular Structure
Elsevier., 1137, 97-108.
https://doi.org/10.1016/j.molstruc.2017.02.012

Vitnik Ž, Popović-Đorđević JB, Vitnik V. Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione. in Journal of Molecular Structure. 2017;1137:97-108.
doi:10.1016/j.molstruc.2017.02.012 .

Vitnik, Željko, Popović-Đorđević, Jelena B., Vitnik, Vesna, "Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione" in Journal of Molecular Structure, 1137 (2017):97-108,
https://doi.org/10.1016/j.molstruc.2017.02.012 . .

TY  - JOUR
AU  - Vitnik, Željko
AU  - Popović-Đorđević, Jelena B.
AU  - Vitnik, Vesna
PY  - 2017
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3036
AB  - The establishment of the most stable structures of 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione, potential anticancer and antimicrobial drug has been investigated in this work. A detailed interpretation of experimental and calculated IR, UV and NMR spectra were reported. The equilibrium geometry, harmonic vibrational frequencies and electronic properties have been investigated with Density Functional Theory using B3LYP/6-311++G(d,p) method. The scaled theoretical wavenumber showed very good agreement with the experimental values. The charge transfer in the molecule was confirmed with NBO analysis. Ultraviolet-visible spectrum was calculated using TD-DFT method and compared with experimental spectrum. The calculated energy and oscillator strength well reproduce the experimental data. The molecular electrostatic potential surface map portrays potential binding sites of the title molecule.
PB  - Elsevier
T2  - Journal of Molecular Structure
T1  - Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione
VL  - 1137
SP  - 97
EP  - 108
DO  - 10.1016/j.molstruc.2017.02.012
ER  - 

@article{
author = "Vitnik, Željko and Popović-Đorđević, Jelena B. and Vitnik, Vesna",
year = "2017",
abstract = "The establishment of the most stable structures of 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione, potential anticancer and antimicrobial drug has been investigated in this work. A detailed interpretation of experimental and calculated IR, UV and NMR spectra were reported. The equilibrium geometry, harmonic vibrational frequencies and electronic properties have been investigated with Density Functional Theory using B3LYP/6-311++G(d,p) method. The scaled theoretical wavenumber showed very good agreement with the experimental values. The charge transfer in the molecule was confirmed with NBO analysis. Ultraviolet-visible spectrum was calculated using TD-DFT method and compared with experimental spectrum. The calculated energy and oscillator strength well reproduce the experimental data. The molecular electrostatic potential surface map portrays potential binding sites of the title molecule.",
publisher = "Elsevier",
journal = "Journal of Molecular Structure",
title = "Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione",
volume = "1137",
pages = "97-108",
doi = "10.1016/j.molstruc.2017.02.012"
}

Vitnik, Ž., Popović-Đorđević, J. B.,& Vitnik, V.. (2017). Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione. in Journal of Molecular Structure
Elsevier., 1137, 97-108.
https://doi.org/10.1016/j.molstruc.2017.02.012

Vitnik Ž, Popović-Đorđević JB, Vitnik V. Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione. in Journal of Molecular Structure. 2017;1137:97-108.
doi:10.1016/j.molstruc.2017.02.012 .

Vitnik, Željko, Popović-Đorđević, Jelena B., Vitnik, Vesna, "Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione" in Journal of Molecular Structure, 1137 (2017):97-108,
https://doi.org/10.1016/j.molstruc.2017.02.012 . .

TY  - JOUR
AU  - Popović-Đorđević, Jelena B.
AU  - Klaus, Anita
AU  - Žižak, Željko
AU  - Matić, Ivana Z.
AU  - Drakulić, Branko
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2667
AB  - Antiproliferative and antibacterial activities of nine glutarimide derivatives (1–9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC50 = 9–27 μM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6–8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 × 10−3 mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.
PB  - Taylor and Francis Ltd
T2  - Journal of Enzyme Inhibition and Medicinal Chemistry
T1  - Antiproliferative and antibacterial activity of some glutarimide derivatives
VL  - 31
SP  - 915
EP  - 923
DO  - 10.3109/14756366.2015.1070844
ER  - 

@article{
author = "Popović-Đorđević, Jelena B. and Klaus, Anita and Žižak, Željko and Matić, Ivana Z. and Drakulić, Branko",
year = "2016",
abstract = "Antiproliferative and antibacterial activities of nine glutarimide derivatives (1–9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC50 = 9–27 μM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6–8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 × 10−3 mol/L). Distinction between more and less active/inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.",
publisher = "Taylor and Francis Ltd",
journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",
title = "Antiproliferative and antibacterial activity of some glutarimide derivatives",
volume = "31",
pages = "915-923",
doi = "10.3109/14756366.2015.1070844"
}

Popović-Đorđević, J. B., Klaus, A., Žižak, Ž., Matić, I. Z.,& Drakulić, B.. (2016). Antiproliferative and antibacterial activity of some glutarimide derivatives. in Journal of Enzyme Inhibition and Medicinal Chemistry
Taylor and Francis Ltd., 31, 915-923.
https://doi.org/10.3109/14756366.2015.1070844

Popović-Đorđević JB, Klaus A, Žižak Ž, Matić IZ, Drakulić B. Antiproliferative and antibacterial activity of some glutarimide derivatives. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2016;31:915-923.
doi:10.3109/14756366.2015.1070844 .

Popović-Đorđević, Jelena B., Klaus, Anita, Žižak, Željko, Matić, Ivana Z., Drakulić, Branko, "Antiproliferative and antibacterial activity of some glutarimide derivatives" in Journal of Enzyme Inhibition and Medicinal Chemistry, 31 (2016):915-923,
https://doi.org/10.3109/14756366.2015.1070844 . .

TY  - JOUR
AU  - Kostić, Aleksandar Ž.
AU  - Pantelić, Nebojša Đ.
AU  - Kaluderovic, Lazar M
AU  - Jonas, Jarmila P
AU  - Dojčinović, Biljana
AU  - Popović-Đorđević, Jelena B.
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1864
AB  - The aim of this study was to evaluate the content of trace elements and physicochemical properties of water samples in the territories of southern Banat and Zemun (Serbia). The contents of twenty-two macro- and microelements were determined using ICP analysis. Prior to this, the typical parameters were evaluated using standard analytical methods. The contents of elements in all studied samples were within the maximum allowed concentrations established by national regulations on the water quality for human use of examined elements, except for Na, Fe, B, Mn, As and Co. The most of elevated metal concentrations were recorded in the samples from Zrenjanin area, with special emphasis on increased concentrations of arsenic. Besides, the higher concentrations of iron and manganese were found in samples S03 and S04, respectively. The increased concentrations of iron, arsenic and manganese in the samples from southern Banat area could be explained by the presence and reductive dissolution of some iron minerals in the subsurface which could contain As or Mn as trace elements. Increased concentration of boron could be the consequence of its leaching from ground caused by the adequate pH value. The obtained results indicate that geology of terrain might be the main cause of elevated concentrations of iron, boron, arsenic and manganese in the study region. Potential human weekly and long-term health risk was determined and expressed through exposure risk assessment. It has been found that only arsenic in sample S07 represents a great weekly risk. On the long-term basis, consumption of waters with elevated concentrations of boron/S05-08/ and manganese/S04, S07 and S08/ can be considered as high health risk. Our study indicates that both risk assessments need to be done, in order to better understand the real risk of increased concentrations of harmful elements on human health.
PB  - Springer, Dordrecht
T2  - Exposure and Health
T1  - Physicochemical Properties of Waters in Southern Banat (Serbia); Potential Leaching of Some Trace Elements from Ground and Human Health Risk
VL  - 8
IS  - 2
SP  - 227
EP  - 238
DO  - 10.1007/s12403-016-0197-7
ER  - 

@article{
author = "Kostić, Aleksandar Ž. and Pantelić, Nebojša Đ. and Kaluderovic, Lazar M and Jonas, Jarmila P and Dojčinović, Biljana and Popović-Đorđević, Jelena B.",
year = "2016",
abstract = "The aim of this study was to evaluate the content of trace elements and physicochemical properties of water samples in the territories of southern Banat and Zemun (Serbia). The contents of twenty-two macro- and microelements were determined using ICP analysis. Prior to this, the typical parameters were evaluated using standard analytical methods. The contents of elements in all studied samples were within the maximum allowed concentrations established by national regulations on the water quality for human use of examined elements, except for Na, Fe, B, Mn, As and Co. The most of elevated metal concentrations were recorded in the samples from Zrenjanin area, with special emphasis on increased concentrations of arsenic. Besides, the higher concentrations of iron and manganese were found in samples S03 and S04, respectively. The increased concentrations of iron, arsenic and manganese in the samples from southern Banat area could be explained by the presence and reductive dissolution of some iron minerals in the subsurface which could contain As or Mn as trace elements. Increased concentration of boron could be the consequence of its leaching from ground caused by the adequate pH value. The obtained results indicate that geology of terrain might be the main cause of elevated concentrations of iron, boron, arsenic and manganese in the study region. Potential human weekly and long-term health risk was determined and expressed through exposure risk assessment. It has been found that only arsenic in sample S07 represents a great weekly risk. On the long-term basis, consumption of waters with elevated concentrations of boron/S05-08/ and manganese/S04, S07 and S08/ can be considered as high health risk. Our study indicates that both risk assessments need to be done, in order to better understand the real risk of increased concentrations of harmful elements on human health.",
publisher = "Springer, Dordrecht",
journal = "Exposure and Health",
title = "Physicochemical Properties of Waters in Southern Banat (Serbia); Potential Leaching of Some Trace Elements from Ground and Human Health Risk",
volume = "8",
number = "2",
pages = "227-238",
doi = "10.1007/s12403-016-0197-7"
}

Kostić, A. Ž., Pantelić, N. Đ., Kaluderovic, L. M., Jonas, J. P., Dojčinović, B.,& Popović-Đorđević, J. B.. (2016). Physicochemical Properties of Waters in Southern Banat (Serbia); Potential Leaching of Some Trace Elements from Ground and Human Health Risk. in Exposure and Health
Springer, Dordrecht., 8(2), 227-238.
https://doi.org/10.1007/s12403-016-0197-7

Kostić AŽ, Pantelić NĐ, Kaluderovic LM, Jonas JP, Dojčinović B, Popović-Đorđević JB. Physicochemical Properties of Waters in Southern Banat (Serbia); Potential Leaching of Some Trace Elements from Ground and Human Health Risk. in Exposure and Health. 2016;8(2):227-238.
doi:10.1007/s12403-016-0197-7 .

Kostić, Aleksandar Ž., Pantelić, Nebojša Đ., Kaluderovic, Lazar M, Jonas, Jarmila P, Dojčinović, Biljana, Popović-Đorđević, Jelena B., "Physicochemical Properties of Waters in Southern Banat (Serbia); Potential Leaching of Some Trace Elements from Ground and Human Health Risk" in Exposure and Health, 8, no. 2 (2016):227-238,
https://doi.org/10.1007/s12403-016-0197-7 . .

TY  - JOUR
AU  - Popović-Đorđević, Jelena B.
AU  - Vitnik, Vesna
AU  - Vitnik, Željko
AU  - Ivanović, Milovan D.
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1633
AB  - Glutarimides, 2,6-dioxopiperidines, are compounds that rarely occur in natural sources, but so far isolated ones exert widespread pharmacological activities, which makes them valuable as potential pharmacotherapeutics. Glutarimides act as androgen receptor antagonists, anti-inflammatory, anxiolytics, antibacterials, and tumor suppressing agents. Some synthetic glutarimide derivatives are already in use as immunosuppressive and sedative (e.g., thalidomide) or anxiolytics (buspirone) drugs. The wide applicability of this class of compounds, justify the interest of scientists to explore new pathways for its syntheses. General methods for synthesis of six-membered imide ring are presented in this paper. These methods include: a) reaction of dicarboxylic acids with ammonia or primary amine, b) reactions of cyclization: amido-acids, diamides, dinitriles, nitrilo-acids, amidonitriles, amido-esters, amidoacyl-chlorides or diacyl-chlorides, c) addition of carbon- monoxide on α, β-unsaturated amides, d) oxidation reactions, e) Michael addition of active methylen compounds on methacrylamide or conjugated amides. Some of the described methods are used for closing glutarimide ring in syntheses of pharmacological active compounds sesbanimide and aldose reductase inhibitors (ARI). Analyses of the geometry, as well as, the spectroscopic analyses (NMR and FT-IR) of some glutarimides are presented due to their broad spectrum of pharmacological activity. To elucidate structures of glutarimides, geometrical parameters of newly synthesized tert-pentyl-1-benzyl-4-methyl-glutarimide- 3-carboxylate (PBMG) are analyzed and compared with the experimental data from X-ray analysis for glutarimide. Moreover, molecular electrostatic potential (MEP) surface which is plotted over the optimized geometry to elucidate the reactivity of PBMG molecule is analyzed. The electronic properties of glutarimide derivatives are explained on the example of thalidomide. The Frontier Molecular Orbital (FMO) and their energies are presented, as well as the energy gap between them.
AB  - U ovom radu dat je prikaz metoda za sintezu šestočlanih cikličnih imida. Glutarimidi, 2,6-dioksopiperidini, su značajna biološka jedinjenja i deluju kao antagonisti adrenogenih receptora, antiinflamatorni agensi, anksiolitici, antivirotici, antibiotici i agensi koji sprečavaju rast pojedinih vrsta tumora. Prikazana je i njihova spektralna analiza (FT-IR i NMR), zbog potvrde stukture, kao i analiza graničnih molekulskih orbitala koja daje prikaz elektronskih svojstava ovih molekula, što je važno zbog njihove biološke aktivnosti. Da bi se predstavila hemijska reaktivnost glutarimida predstavljen je molekulski elektronski potencijal (MEP) iz prethodno optimizovane geometrije reprezentativnog primera terc-pentil-1- -benzil-4-metil-glutarimid-3-karboksilata (skraćenica PBMG). Elektronska svojstva su objašnjena na primeru talidomida.
PB  - Assoc Chemical Engineers Serbia, Belgrade
T2  - Hemijska industrija
T1  - Glutarimides: Biological activity, general synthetic methods and physicochemical properties
T1  - Glutarimidi - biološka aktivnost, opšti postupci za sintezu i fizičko-hemijske karakteristike
VL  - 69
IS  - 5
SP  - 523
EP  - 536
DO  - 10.2298/HEMIND140701073P
ER  - 

@article{
author = "Popović-Đorđević, Jelena B. and Vitnik, Vesna and Vitnik, Željko and Ivanović, Milovan D.",
year = "2015",
abstract = "Glutarimides, 2,6-dioxopiperidines, are compounds that rarely occur in natural sources, but so far isolated ones exert widespread pharmacological activities, which makes them valuable as potential pharmacotherapeutics. Glutarimides act as androgen receptor antagonists, anti-inflammatory, anxiolytics, antibacterials, and tumor suppressing agents. Some synthetic glutarimide derivatives are already in use as immunosuppressive and sedative (e.g., thalidomide) or anxiolytics (buspirone) drugs. The wide applicability of this class of compounds, justify the interest of scientists to explore new pathways for its syntheses. General methods for synthesis of six-membered imide ring are presented in this paper. These methods include: a) reaction of dicarboxylic acids with ammonia or primary amine, b) reactions of cyclization: amido-acids, diamides, dinitriles, nitrilo-acids, amidonitriles, amido-esters, amidoacyl-chlorides or diacyl-chlorides, c) addition of carbon- monoxide on α, β-unsaturated amides, d) oxidation reactions, e) Michael addition of active methylen compounds on methacrylamide or conjugated amides. Some of the described methods are used for closing glutarimide ring in syntheses of pharmacological active compounds sesbanimide and aldose reductase inhibitors (ARI). Analyses of the geometry, as well as, the spectroscopic analyses (NMR and FT-IR) of some glutarimides are presented due to their broad spectrum of pharmacological activity. To elucidate structures of glutarimides, geometrical parameters of newly synthesized tert-pentyl-1-benzyl-4-methyl-glutarimide- 3-carboxylate (PBMG) are analyzed and compared with the experimental data from X-ray analysis for glutarimide. Moreover, molecular electrostatic potential (MEP) surface which is plotted over the optimized geometry to elucidate the reactivity of PBMG molecule is analyzed. The electronic properties of glutarimide derivatives are explained on the example of thalidomide. The Frontier Molecular Orbital (FMO) and their energies are presented, as well as the energy gap between them., U ovom radu dat je prikaz metoda za sintezu šestočlanih cikličnih imida. Glutarimidi, 2,6-dioksopiperidini, su značajna biološka jedinjenja i deluju kao antagonisti adrenogenih receptora, antiinflamatorni agensi, anksiolitici, antivirotici, antibiotici i agensi koji sprečavaju rast pojedinih vrsta tumora. Prikazana je i njihova spektralna analiza (FT-IR i NMR), zbog potvrde stukture, kao i analiza graničnih molekulskih orbitala koja daje prikaz elektronskih svojstava ovih molekula, što je važno zbog njihove biološke aktivnosti. Da bi se predstavila hemijska reaktivnost glutarimida predstavljen je molekulski elektronski potencijal (MEP) iz prethodno optimizovane geometrije reprezentativnog primera terc-pentil-1- -benzil-4-metil-glutarimid-3-karboksilata (skraćenica PBMG). Elektronska svojstva su objašnjena na primeru talidomida.",
publisher = "Assoc Chemical Engineers Serbia, Belgrade",
journal = "Hemijska industrija",
title = "Glutarimides: Biological activity, general synthetic methods and physicochemical properties, Glutarimidi - biološka aktivnost, opšti postupci za sintezu i fizičko-hemijske karakteristike",
volume = "69",
number = "5",
pages = "523-536",
doi = "10.2298/HEMIND140701073P"
}

Popović-Đorđević, J. B., Vitnik, V., Vitnik, Ž.,& Ivanović, M. D.. (2015). Glutarimides: Biological activity, general synthetic methods and physicochemical properties. in Hemijska industrija
Assoc Chemical Engineers Serbia, Belgrade., 69(5), 523-536.
https://doi.org/10.2298/HEMIND140701073P

Popović-Đorđević JB, Vitnik V, Vitnik Ž, Ivanović MD. Glutarimides: Biological activity, general synthetic methods and physicochemical properties. in Hemijska industrija. 2015;69(5):523-536.
doi:10.2298/HEMIND140701073P .

Popović-Đorđević, Jelena B., Vitnik, Vesna, Vitnik, Željko, Ivanović, Milovan D., "Glutarimides: Biological activity, general synthetic methods and physicochemical properties" in Hemijska industrija, 69, no. 5 (2015):523-536,
https://doi.org/10.2298/HEMIND140701073P . .

TY  - JOUR
AU  - Vitnik, Vesna
AU  - Ivanović, Milovan D.
AU  - Vitnik, Željko
AU  - Đorđević, Jelena B.
AU  - Žižak, Željko
AU  - Juranić, Zorica
AU  - Juranić, Ivan
PY  - 2009
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/576
AB  - Phase-transfer-catalyzed (PTC) reactions of ketones with bromoform and aqueous lithium hydroxide in alcoholic solvent result in the formation of ,-unsaturated carboxylic acids. The reaction was performed at room temperature for 24h. The corresponding conjugated acids were obtained from cyclic or aromatic ketones, whereas bromo acids were obtained from 4-oxo-piperidine-1- carboxylic acid ethyl ester (13) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (14).
T2  - Synthetic Communications
T1  - One-step conversion of ketones to conjugated acids using bromoform
VL  - 39
IS  - 8
SP  - 1457
EP  - 1471
DO  - 10.1080/00397910802531955
ER  - 

@article{
author = "Vitnik, Vesna and Ivanović, Milovan D. and Vitnik, Željko and Đorđević, Jelena B. and Žižak, Željko and Juranić, Zorica and Juranić, Ivan",
year = "2009",
abstract = "Phase-transfer-catalyzed (PTC) reactions of ketones with bromoform and aqueous lithium hydroxide in alcoholic solvent result in the formation of ,-unsaturated carboxylic acids. The reaction was performed at room temperature for 24h. The corresponding conjugated acids were obtained from cyclic or aromatic ketones, whereas bromo acids were obtained from 4-oxo-piperidine-1- carboxylic acid ethyl ester (13) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (14).",
journal = "Synthetic Communications",
title = "One-step conversion of ketones to conjugated acids using bromoform",
volume = "39",
number = "8",
pages = "1457-1471",
doi = "10.1080/00397910802531955"
}

Vitnik, V., Ivanović, M. D., Vitnik, Ž., Đorđević, J. B., Žižak, Ž., Juranić, Z.,& Juranić, I.. (2009). One-step conversion of ketones to conjugated acids using bromoform. in Synthetic Communications, 39(8), 1457-1471.
https://doi.org/10.1080/00397910802531955

Vitnik V, Ivanović MD, Vitnik Ž, Đorđević JB, Žižak Ž, Juranić Z, Juranić I. One-step conversion of ketones to conjugated acids using bromoform. in Synthetic Communications. 2009;39(8):1457-1471.
doi:10.1080/00397910802531955 .

Vitnik, Vesna, Ivanović, Milovan D., Vitnik, Željko, Đorđević, Jelena B., Žižak, Željko, Juranić, Zorica, Juranić, Ivan, "One-step conversion of ketones to conjugated acids using bromoform" in Synthetic Communications, 39, no. 8 (2009):1457-1471,
https://doi.org/10.1080/00397910802531955 . .

TY  - JOUR
AU  - Popović-Đorđević, Jelena B.
AU  - Ivanović, Milovan D.
AU  - Kiricojević, Vesna
PY  - 2005
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2678
AB  - The synthesis of various functionalized or spirobicyclic glutarimides by a novel tandem process has been disclosed. The reaction involves a base-catalyzed Michael addition of active methylene compounds to secondary conjugated amides, followed by intramolecular N-acylation of the carboxamido group. It provides a relatively general and simple access to useful synthetic intermediaries and potentially active pharmacological compounds. In addition, a novel group of spirobicyclic systems has been synthesized. (c) 2005 Elsevier Ltd. All rights reserved.
PB  - Oxford : Pergamon-Elsevier Science Ltd
T2  - Tetrahedron Letters
T1  - A novel tandem process leading to functionalized glutarimides
VL  - 46
IS  - 15
SP  - 2611
EP  - 2614
DO  - 10.1016/j.tetlet.2005.02.087
ER  - 

@article{
author = "Popović-Đorđević, Jelena B. and Ivanović, Milovan D. and Kiricojević, Vesna",
year = "2005",
abstract = "The synthesis of various functionalized or spirobicyclic glutarimides by a novel tandem process has been disclosed. The reaction involves a base-catalyzed Michael addition of active methylene compounds to secondary conjugated amides, followed by intramolecular N-acylation of the carboxamido group. It provides a relatively general and simple access to useful synthetic intermediaries and potentially active pharmacological compounds. In addition, a novel group of spirobicyclic systems has been synthesized. (c) 2005 Elsevier Ltd. All rights reserved.",
publisher = "Oxford : Pergamon-Elsevier Science Ltd",
journal = "Tetrahedron Letters",
title = "A novel tandem process leading to functionalized glutarimides",
volume = "46",
number = "15",
pages = "2611-2614",
doi = "10.1016/j.tetlet.2005.02.087"
}

Popović-Đorđević, J. B., Ivanović, M. D.,& Kiricojević, V.. (2005). A novel tandem process leading to functionalized glutarimides. in Tetrahedron Letters
Oxford : Pergamon-Elsevier Science Ltd., 46(15), 2611-2614.
https://doi.org/10.1016/j.tetlet.2005.02.087

Popović-Đorđević JB, Ivanović MD, Kiricojević V. A novel tandem process leading to functionalized glutarimides. in Tetrahedron Letters. 2005;46(15):2611-2614.
doi:10.1016/j.tetlet.2005.02.087 .

Popović-Đorđević, Jelena B., Ivanović, Milovan D., Kiricojević, Vesna, "A novel tandem process leading to functionalized glutarimides" in Tetrahedron Letters, 46, no. 15 (2005):2611-2614,
https://doi.org/10.1016/j.tetlet.2005.02.087 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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