TY  - JOUR
AU  - Ivanović, Milovan
AU  - Mićović, Ivan V.
AU  - Vuckovic, S
AU  - Prostran, M
AU  - Todorović, Zoran B.
AU  - Kiricojevic, VD
AU  - Popović-Đorđević, Jelena
AU  - Došen-Mićović, Ljiljana
PY  - 2004
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/650
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 and Mićović, Ivan V. and Vuckovic, S and Prostran, M and Todorović, Zoran B. and Kiricojevic, VD and Popović-Đorđević, Jelena 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., Mićović, I. V., Vuckovic, S., Prostran, M., Todorović, Z. B., Kiricojevic, V., Popović-Đorđević, J.,& 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 M, Mićović IV, Vuckovic S, Prostran M, Todorović ZB, Kiricojevic V, Popović-Đorđević J, 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, Mićović, Ivan V., Vuckovic, S, Prostran, M, Todorović, Zoran B., Kiricojevic, VD, Popović-Đorđević, Jelena, 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  - Ivanović, Milovan
AU  - Mićović, Ivan V.
AU  - Vuckovic, S
AU  - Prostran, M
AU  - Todorović, Zoran B.
AU  - Ivanovic, ER
AU  - Kiricojevic, VD
AU  - Popović-Đorđević, Jelena
AU  - Došen-Mićović, Ljiljana
PY  - 2004
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/681
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 and Mićović, Ivan V. and Vuckovic, S and Prostran, M and Todorović, Zoran B. and Ivanovic, ER and Kiricojevic, VD and Popović-Đorđević, Jelena 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., Mićović, I. V., Vuckovic, S., Prostran, M., Todorović, Z. B., Ivanovic, E., Kiricojevic, V., Popović-Đorđević, J.,& 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 M, Mićović IV, Vuckovic S, Prostran M, Todorović ZB, Ivanovic E, Kiricojevic V, Popović-Đorđević J, 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, Mićović, Ivan V., Vuckovic, S, Prostran, M, Todorović, Zoran B., Ivanovic, ER, Kiricojevic, VD, Popović-Đorđević, Jelena, 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  - Kiricojevic, VD
AU  - Ivanović, Milovan
AU  - Mićović, Ivan V.
AU  - Popović-Đorđević, Jelena
AU  - Roglić, Goran
AU  - Došen-Mićović, Ljiljana
PY  - 2002
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/529
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 = "Kiricojevic, VD and Ivanović, Milovan and Mićović, Ivan V. and Popović-Đorđević, Jelena 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"
}

Kiricojevic, V., Ivanović, M., Mićović, I. V., Popović-Đorđević, J., 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

Kiricojevic V, Ivanović M, Mićović IV, Popović-Đorđević J, 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 .

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

TY  - JOUR
AU  - Mićović, Ivan V.
AU  - Ivanović, Milovan
AU  - Vuckovic, SM
AU  - Prostran, MS
AU  - Došen-Mićović, Ljiljana
AU  - Kiricojevic, VD
PY  - 2000
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/442
AB  - The synthesis of 4-methyl fentanyl, a prototype of a novel class of fentanyl analogues has been effected in 5 steps, starting from N-ethoxycarbonyl-4-piperidone (similar to 20% overall yield). In the key step, N-phenylation of secondary aliphatic amide intermediate was achieved by a novel reaction, using diphenyliodonium chloride for the phenyl group transfer. Preliminary pharmacological results indicate that 4-methyl fentanyl is a super potent narcotic analgesic, about four times more potent than fentanyl. (C) 2000 Elsevier Science Ltd. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic and Medicinal Chemistry Letters
T1  - The synthesis and preliminary pharmacological evaluation of 4-methyl fentanyl
VL  - 10
IS  - 17
SP  - 2011
EP  - 2014
DO  - 10.1016/S0960-894X(00)00394-2
ER  - 

@article{
author = "Mićović, Ivan V. and Ivanović, Milovan and Vuckovic, SM and Prostran, MS and Došen-Mićović, Ljiljana and Kiricojevic, VD",
year = "2000",
abstract = "The synthesis of 4-methyl fentanyl, a prototype of a novel class of fentanyl analogues has been effected in 5 steps, starting from N-ethoxycarbonyl-4-piperidone (similar to 20% overall yield). In the key step, N-phenylation of secondary aliphatic amide intermediate was achieved by a novel reaction, using diphenyliodonium chloride for the phenyl group transfer. Preliminary pharmacological results indicate that 4-methyl fentanyl is a super potent narcotic analgesic, about four times more potent than fentanyl. (C) 2000 Elsevier Science Ltd. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic and Medicinal Chemistry Letters",
title = "The synthesis and preliminary pharmacological evaluation of 4-methyl fentanyl",
volume = "10",
number = "17",
pages = "2011-2014",
doi = "10.1016/S0960-894X(00)00394-2"
}

Mićović, I. V., Ivanović, M., Vuckovic, S., Prostran, M., Došen-Mićović, L.,& Kiricojevic, V.. (2000). The synthesis and preliminary pharmacological evaluation of 4-methyl fentanyl. in Bioorganic and Medicinal Chemistry Letters
Pergamon-Elsevier Science Ltd, Oxford., 10(17), 2011-2014.
https://doi.org/10.1016/S0960-894X(00)00394-2

Mićović IV, Ivanović M, Vuckovic S, Prostran M, Došen-Mićović L, Kiricojevic V. The synthesis and preliminary pharmacological evaluation of 4-methyl fentanyl. in Bioorganic and Medicinal Chemistry Letters. 2000;10(17):2011-2014.
doi:10.1016/S0960-894X(00)00394-2 .

Mićović, Ivan V., Ivanović, Milovan, Vuckovic, SM, Prostran, MS, Došen-Mićović, Ljiljana, Kiricojevic, VD, "The synthesis and preliminary pharmacological evaluation of 4-methyl fentanyl" in Bioorganic and Medicinal Chemistry Letters, 10, no. 17 (2000):2011-2014,
https://doi.org/10.1016/S0960-894X(00)00394-2 . .

TY  - JOUR
AU  - Mićović, Ivan V.
AU  - Ivanović, Milovan
AU  - Vuckovic, S
AU  - Jovanovic-Micic, D
AU  - Beleslin, D.
AU  - Došen-Mićović, Ljiljana
AU  - Kiricojevic, VD
PY  - 1998
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/370
AB  - A novel analogue of fentanyl, 3-carbomethoxyfentanyl, or "iso-carfentanil", was synthesized by a simple and efficient route. In the first step phenethylamine was condensed with two equivalents of methyl acrylate to afford the amino-diester Ib in quantitative yield. Dieckmann cyclization of this intermediate yielded 3-carbomethoxy N-phenethyl-4-piperidone 2 in ca. 80% yield, after mild hydrolysis. Condensation of this beta-keto ester with aniline in acetic acid gave the stable enamine 3 (70% yield) which was then reduced with NaBH3CN in methanol at pH approximate to 5, to yield 4-anilino-3-carbomethoxy-N-phenethyl piperidine, quantitatively. This intermediate was obtained as a 50:50 mixture of the (+/-) cis and (+/-) trans isomers, 4a and 4b, respectively. After the mixture of diastereoisomers was separated on a neutral aluminium oxide column, the pure 4a and 4b isomers were acylated with propionyl chloride, thus completing the synthesis of 3-carbomethoxy fentanyl 5a and 5b. The relative stereochemistry was H-1-NMR spectroscopy. These compounds present regioisomers of determined by carfentanil, one of the most potent narcotic analgesic known to date. Preliminary pharmacological evaluation (tail-withdrawal test in rats) revealed substantially reduced potency of both diastereoisomers, the (+/-) trans 5b in particular, compared to carfentanil. The computational (molecular mechanics) search of the low energy regions of the conformational space of the cis 5a and trans 5b isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible, the trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - The synthesis, pharmacological evaluation and conformational analysis of (+/-)cis- and (+/-)trans3-carbomethoxy fentanyl-"iso-carfentanil"
VL  - 63
IS  - 2
SP  - 93
EP  - 112
UR  - https://hdl.handle.net/21.15107/rcub_cherry_370
ER  - 

@article{
author = "Mićović, Ivan V. and Ivanović, Milovan and Vuckovic, S and Jovanovic-Micic, D and Beleslin, D. and Došen-Mićović, Ljiljana and Kiricojevic, VD",
year = "1998",
abstract = "A novel analogue of fentanyl, 3-carbomethoxyfentanyl, or "iso-carfentanil", was synthesized by a simple and efficient route. In the first step phenethylamine was condensed with two equivalents of methyl acrylate to afford the amino-diester Ib in quantitative yield. Dieckmann cyclization of this intermediate yielded 3-carbomethoxy N-phenethyl-4-piperidone 2 in ca. 80% yield, after mild hydrolysis. Condensation of this beta-keto ester with aniline in acetic acid gave the stable enamine 3 (70% yield) which was then reduced with NaBH3CN in methanol at pH approximate to 5, to yield 4-anilino-3-carbomethoxy-N-phenethyl piperidine, quantitatively. This intermediate was obtained as a 50:50 mixture of the (+/-) cis and (+/-) trans isomers, 4a and 4b, respectively. After the mixture of diastereoisomers was separated on a neutral aluminium oxide column, the pure 4a and 4b isomers were acylated with propionyl chloride, thus completing the synthesis of 3-carbomethoxy fentanyl 5a and 5b. The relative stereochemistry was H-1-NMR spectroscopy. These compounds present regioisomers of determined by carfentanil, one of the most potent narcotic analgesic known to date. Preliminary pharmacological evaluation (tail-withdrawal test in rats) revealed substantially reduced potency of both diastereoisomers, the (+/-) trans 5b in particular, compared to carfentanil. The computational (molecular mechanics) search of the low energy regions of the conformational space of the cis 5a and trans 5b isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible, the trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "The synthesis, pharmacological evaluation and conformational analysis of (+/-)cis- and (+/-)trans3-carbomethoxy fentanyl-"iso-carfentanil"",
volume = "63",
number = "2",
pages = "93-112",
url = "https://hdl.handle.net/21.15107/rcub_cherry_370"
}

Mićović, I. V., Ivanović, M., Vuckovic, S., Jovanovic-Micic, D., Beleslin, D., Došen-Mićović, L.,& Kiricojevic, V.. (1998). The synthesis, pharmacological evaluation and conformational analysis of (+/-)cis- and (+/-)trans3-carbomethoxy fentanyl-"iso-carfentanil". in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 63(2), 93-112.
https://hdl.handle.net/21.15107/rcub_cherry_370

Mićović IV, Ivanović M, Vuckovic S, Jovanovic-Micic D, Beleslin D, Došen-Mićović L, Kiricojevic V. The synthesis, pharmacological evaluation and conformational analysis of (+/-)cis- and (+/-)trans3-carbomethoxy fentanyl-"iso-carfentanil". in Journal of the Serbian Chemical Society. 1998;63(2):93-112.
https://hdl.handle.net/21.15107/rcub_cherry_370 .

Mićović, Ivan V., Ivanović, Milovan, Vuckovic, S, Jovanovic-Micic, D, Beleslin, D., Došen-Mićović, Ljiljana, Kiricojevic, VD, "The synthesis, pharmacological evaluation and conformational analysis of (+/-)cis- and (+/-)trans3-carbomethoxy fentanyl-"iso-carfentanil"" in Journal of the Serbian Chemical Society, 63, no. 2 (1998):93-112,
https://hdl.handle.net/21.15107/rcub_cherry_370 .

TY  - JOUR
AU  - Mićović, Ivan V.
AU  - Ivanović, Milovan
AU  - Jovanovic-Micic, D
AU  - Beleslin, D.
AU  - Došen-Mićović, Ljiljana
AU  - Kiricojevic, VD
PY  - 1998
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/381
AB  - The synthesis of a novel analogue of fentanyl, 3-carbomethoxy fentanyl or "iso-carfentanil" has been accomplished in five steps, by simple and efficient route, starting from phenethyl amine and methyl acrylate. Both (+/-)  lt (cis)under bar gt  and -(+/-)  lt (trans)under bar gt  isomers were obtained in pure form and tested pharmacologically for the central analgesic activity: Preliminary results (rat-withdrawal test) revealed significant but substantially reduced potency of both isomers, the  lt (trans)under bar gt  in particular, compared to carfentanil. The computational (molecular mechanics) search of the conformational space low energy regions of  lt (5a)under bar gt  ((+/-)  lt (cis)under bar gt ) and  lt (5b)under bar gt  ((+/-)  lt (trans)under bar gt  isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl.
PB  - Walter De Gruyter Gmbh, Berlin
T2  - Heterocyclic Communications
T1  - 3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis
VL  - 4
IS  - 2
SP  - 171
EP  - 179
UR  - https://hdl.handle.net/21.15107/rcub_cherry_381
ER  - 

@article{
author = "Mićović, Ivan V. and Ivanović, Milovan and Jovanovic-Micic, D and Beleslin, D. and Došen-Mićović, Ljiljana and Kiricojevic, VD",
year = "1998",
abstract = "The synthesis of a novel analogue of fentanyl, 3-carbomethoxy fentanyl or "iso-carfentanil" has been accomplished in five steps, by simple and efficient route, starting from phenethyl amine and methyl acrylate. Both (+/-)  lt (cis)under bar gt  and -(+/-)  lt (trans)under bar gt  isomers were obtained in pure form and tested pharmacologically for the central analgesic activity: Preliminary results (rat-withdrawal test) revealed significant but substantially reduced potency of both isomers, the  lt (trans)under bar gt  in particular, compared to carfentanil. The computational (molecular mechanics) search of the conformational space low energy regions of  lt (5a)under bar gt  ((+/-)  lt (cis)under bar gt ) and  lt (5b)under bar gt  ((+/-)  lt (trans)under bar gt  isomers revealed the difference in their conformational mobility. Besides being more conformationaly flexible trans isomer has unfavorable orientation of the 4-N-phenylpropanamide group compared to the other active analogs of fentanyl. This is believed to be the reason of its reduced potency relative to fentanyl.",
publisher = "Walter De Gruyter Gmbh, Berlin",
journal = "Heterocyclic Communications",
title = "3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis",
volume = "4",
number = "2",
pages = "171-179",
url = "https://hdl.handle.net/21.15107/rcub_cherry_381"
}

Mićović, I. V., Ivanović, M., Jovanovic-Micic, D., Beleslin, D., Došen-Mićović, L.,& Kiricojevic, V.. (1998). 3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis. in Heterocyclic Communications
Walter De Gruyter Gmbh, Berlin., 4(2), 171-179.
https://hdl.handle.net/21.15107/rcub_cherry_381

Mićović IV, Ivanović M, Jovanovic-Micic D, Beleslin D, Došen-Mićović L, Kiricojevic V. 3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis. in Heterocyclic Communications. 1998;4(2):171-179.
https://hdl.handle.net/21.15107/rcub_cherry_381 .

Mićović, Ivan V., Ivanović, Milovan, Jovanovic-Micic, D, Beleslin, D., Došen-Mićović, Ljiljana, Kiricojevic, VD, "3-carbomethoxy fentanyl: Synthesis, pharmacology and conformational analysis" in Heterocyclic Communications, 4, no. 2 (1998):171-179,
https://hdl.handle.net/21.15107/rcub_cherry_381 .

TY  - JOUR
AU  - Mićović, Ivan V.
AU  - Ivanović, Milovan
AU  - Roglić, Goran
AU  - Kiricojevic, VD
AU  - Popovic, JB
PY  - 1996
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2239
AB  - A novel and efficient method for the preparation of secondary amines by reductive amination of carbonyl compounds with primary amines has been developed, The reduction, effected with metallic magnesium in methanol, utilizing triethylamine-acetic acid as a buffer, gave pure secondary amines, mostly in good yields (65-80%). No formation of tertiary amines or alcohols was observed. Use of ammonium acetate as an amino component gave primary amines in modest yields (ca. 50%), together with variable amounts of secondary amines. Enamines failed to undergo reduction. The method is inexpensive, relatively rapid, operationally simple and suitable for large-scale preparations, In addition, a simple method for separation of primary amines from secondary ones has been developed.
PB  - Royal Soc Chemistry, Cambridge
T2  - Journal of the Chemical Society. Perkin Transactions 1
T1  - Preparation of secondary amines by reductive amination with metallic magnesium
IS  - 3
SP  - 265
EP  - 269
DO  - 10.1039/p19960000265
ER  - 

@article{
author = "Mićović, Ivan V. and Ivanović, Milovan and Roglić, Goran and Kiricojevic, VD and Popovic, JB",
year = "1996",
abstract = "A novel and efficient method for the preparation of secondary amines by reductive amination of carbonyl compounds with primary amines has been developed, The reduction, effected with metallic magnesium in methanol, utilizing triethylamine-acetic acid as a buffer, gave pure secondary amines, mostly in good yields (65-80%). No formation of tertiary amines or alcohols was observed. Use of ammonium acetate as an amino component gave primary amines in modest yields (ca. 50%), together with variable amounts of secondary amines. Enamines failed to undergo reduction. The method is inexpensive, relatively rapid, operationally simple and suitable for large-scale preparations, In addition, a simple method for separation of primary amines from secondary ones has been developed.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Journal of the Chemical Society. Perkin Transactions 1",
title = "Preparation of secondary amines by reductive amination with metallic magnesium",
number = "3",
pages = "265-269",
doi = "10.1039/p19960000265"
}

Mićović, I. V., Ivanović, M., Roglić, G., Kiricojevic, V.,& Popovic, J.. (1996). Preparation of secondary amines by reductive amination with metallic magnesium. in Journal of the Chemical Society. Perkin Transactions 1
Royal Soc Chemistry, Cambridge.(3), 265-269.
https://doi.org/10.1039/p19960000265

Mićović IV, Ivanović M, Roglić G, Kiricojevic V, Popovic J. Preparation of secondary amines by reductive amination with metallic magnesium. in Journal of the Chemical Society. Perkin Transactions 1. 1996;(3):265-269.
doi:10.1039/p19960000265 .

Mićović, Ivan V., Ivanović, Milovan, Roglić, Goran, Kiricojevic, VD, Popovic, JB, "Preparation of secondary amines by reductive amination with metallic magnesium" in Journal of the Chemical Society. Perkin Transactions 1, no. 3 (1996):265-269,
https://doi.org/10.1039/p19960000265 . .

TY  - JOUR
AU  - Mićović, Ivan V.
AU  - Roglić, Goran
AU  - Ivanović, Milovan
AU  - DosenMicovic, L
AU  - Kiricojevic, VD
AU  - Popovic, JB
PY  - 1996
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2248
AB  - Fentanyl, sufentanil and alfentanil are clinically widely used anaesthetics and are structurally related to drugs with entirely different pharmacological activity such as droperidol, loperamide and lorcainide, etc. Therefore, in order to test their pharmacological activity, lactam analogues of fentanyl, a novel class of compounds, have been synthesized. In the first step, various primary amines have been selectively added to 1 equiv, of alpha,beta-unsaturated esters, to afford the beta-amino esters. N-Acylation of these intermediates with dimethyl malonate yields the amido esters, which have been further subjected to Dieckmann-type cyclization, to produce the corresponding 3-methoxycarbonylpiperidine-2,4-diones. The cyclization has been effected under phase-transfer conditions, utilizing potassium carbonate as base and 18-crown-6 as catalyst, This eliminates the need for strong and hazardous bases such as molten sodium or NaH, In the next step, acid hydrolysis and decarboxylation furnish the substituted piperidine-2,4-diones in good yields, as pure products. Alkylation of the N-phenethylpiperidine-2,4-dione with methyl iodide and potassium carbonate in DMSO gives the 3,3-dimethyl derivative, The alkylation procedure is also applicable to other alkylating agents. Reductive amination of the prepared piperidine-2,4-diones with aniline and NaBH3CN in buffered methanol gives the corresponding pure 4-anilino-2-piperidones. The lactam function can be readily reduced (NaBH4-BF3 . Et(2)O), as exemplified with the 3,3-dimethyl derivative, thus providing access to additional fentanyl analogues, not readily accessible by other routes. The synthesis is completed by N-acylation of the anilines with propionyl chloride using triethylamine as base. The prepared 4-propionanilido-2-piperidones and 4-propionanilidopiperidines are expected to provide useful structure-activity relationship data in the pharmacological studies.
PB  - Royal Soc Chemistry, Cambridge
T2  - Journal of the Chemical Society. Perkin Transactions 1
T1  - The synthesis of lactam analogues of fentanyl
IS  - 16
SP  - 2041
EP  - 2050
DO  - 10.1039/p19960002041
ER  - 

@article{
author = "Mićović, Ivan V. and Roglić, Goran and Ivanović, Milovan and DosenMicovic, L and Kiricojevic, VD and Popovic, JB",
year = "1996",
abstract = "Fentanyl, sufentanil and alfentanil are clinically widely used anaesthetics and are structurally related to drugs with entirely different pharmacological activity such as droperidol, loperamide and lorcainide, etc. Therefore, in order to test their pharmacological activity, lactam analogues of fentanyl, a novel class of compounds, have been synthesized. In the first step, various primary amines have been selectively added to 1 equiv, of alpha,beta-unsaturated esters, to afford the beta-amino esters. N-Acylation of these intermediates with dimethyl malonate yields the amido esters, which have been further subjected to Dieckmann-type cyclization, to produce the corresponding 3-methoxycarbonylpiperidine-2,4-diones. The cyclization has been effected under phase-transfer conditions, utilizing potassium carbonate as base and 18-crown-6 as catalyst, This eliminates the need for strong and hazardous bases such as molten sodium or NaH, In the next step, acid hydrolysis and decarboxylation furnish the substituted piperidine-2,4-diones in good yields, as pure products. Alkylation of the N-phenethylpiperidine-2,4-dione with methyl iodide and potassium carbonate in DMSO gives the 3,3-dimethyl derivative, The alkylation procedure is also applicable to other alkylating agents. Reductive amination of the prepared piperidine-2,4-diones with aniline and NaBH3CN in buffered methanol gives the corresponding pure 4-anilino-2-piperidones. The lactam function can be readily reduced (NaBH4-BF3 . Et(2)O), as exemplified with the 3,3-dimethyl derivative, thus providing access to additional fentanyl analogues, not readily accessible by other routes. The synthesis is completed by N-acylation of the anilines with propionyl chloride using triethylamine as base. The prepared 4-propionanilido-2-piperidones and 4-propionanilidopiperidines are expected to provide useful structure-activity relationship data in the pharmacological studies.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Journal of the Chemical Society. Perkin Transactions 1",
title = "The synthesis of lactam analogues of fentanyl",
number = "16",
pages = "2041-2050",
doi = "10.1039/p19960002041"
}

Mićović, I. V., Roglić, G., Ivanović, M., DosenMicovic, L., Kiricojevic, V.,& Popovic, J.. (1996). The synthesis of lactam analogues of fentanyl. in Journal of the Chemical Society. Perkin Transactions 1
Royal Soc Chemistry, Cambridge.(16), 2041-2050.
https://doi.org/10.1039/p19960002041

Mićović IV, Roglić G, Ivanović M, DosenMicovic L, Kiricojevic V, Popovic J. The synthesis of lactam analogues of fentanyl. in Journal of the Chemical Society. Perkin Transactions 1. 1996;(16):2041-2050.
doi:10.1039/p19960002041 .

Mićović, Ivan V., Roglić, Goran, Ivanović, Milovan, DosenMicovic, L, Kiricojevic, VD, Popovic, JB, "The synthesis of lactam analogues of fentanyl" in Journal of the Chemical Society. Perkin Transactions 1, no. 16 (1996):2041-2050,
https://doi.org/10.1039/p19960002041 . .

TY  - JOUR
AU  - DosenMicovic, L
AU  - Roglić, Goran
AU  - Mićović, Ivan V.
AU  - Ivanović, Milovan
PY  - 1996
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2583
AB  - The computational method, based on molecular mechanics, with Monte Carlo type searching in dihedral angle space, was applied to the study of seven physiologically highly active fentanyl analogs, with different substituents in a phenethyl side chain. The low energy regions of the conformational space of these molecules have been compared in an effort to establish the receptor-recognized conformation of a phenethyl side chain, and to explain the mechanisms by which a hydroxyl substituent increases potency of the fentanyl analogs. It has been found that the extended conformation of a phenethyl side chain is the only one available to all the active analogs of fentanyl. Activities of the compounds with alkyl substituents in the phenethyl side chain correlate with their hydrophobicities, A hydroxyl substituent affects potency by reducing the flexibility of the phenethyl side chain, by reducing the energy difference between the global minimum and the receptor-recognized conformation and by specific interactions with the receptor.
PB  - John Wiley & Sons Ltd, W Sussex
T2  - Electronic Journal of Theoretical Chemistry
T1  - Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent
VL  - 1
SP  - 199
EP  - 210
UR  - https://hdl.handle.net/21.15107/rcub_cherry_2583
ER  - 

@article{
author = "DosenMicovic, L and Roglić, Goran and Mićović, Ivan V. and Ivanović, Milovan",
year = "1996",
abstract = "The computational method, based on molecular mechanics, with Monte Carlo type searching in dihedral angle space, was applied to the study of seven physiologically highly active fentanyl analogs, with different substituents in a phenethyl side chain. The low energy regions of the conformational space of these molecules have been compared in an effort to establish the receptor-recognized conformation of a phenethyl side chain, and to explain the mechanisms by which a hydroxyl substituent increases potency of the fentanyl analogs. It has been found that the extended conformation of a phenethyl side chain is the only one available to all the active analogs of fentanyl. Activities of the compounds with alkyl substituents in the phenethyl side chain correlate with their hydrophobicities, A hydroxyl substituent affects potency by reducing the flexibility of the phenethyl side chain, by reducing the energy difference between the global minimum and the receptor-recognized conformation and by specific interactions with the receptor.",
publisher = "John Wiley & Sons Ltd, W Sussex",
journal = "Electronic Journal of Theoretical Chemistry",
title = "Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent",
volume = "1",
pages = "199-210",
url = "https://hdl.handle.net/21.15107/rcub_cherry_2583"
}

DosenMicovic, L., Roglić, G., Mićović, I. V.,& Ivanović, M.. (1996). Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent. in Electronic Journal of Theoretical Chemistry
John Wiley & Sons Ltd, W Sussex., 1, 199-210.
https://hdl.handle.net/21.15107/rcub_cherry_2583

DosenMicovic L, Roglić G, Mićović IV, Ivanović M. Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent. in Electronic Journal of Theoretical Chemistry. 1996;1:199-210.
https://hdl.handle.net/21.15107/rcub_cherry_2583 .

DosenMicovic, L, Roglić, Goran, Mićović, Ivan V., Ivanović, Milovan, "Conformational study of fentanyl and its analogs .1. Conformational space of the N-phenethyl substituent" in Electronic Journal of Theoretical Chemistry, 1 (1996):199-210,
https://hdl.handle.net/21.15107/rcub_cherry_2583 .

TY  - JOUR
AU  - Mićović, Ivan V.
AU  - Ivanović, Milovan
AU  - Piatak, David M.
AU  - Bojić, Vera D.
PY  - 1991
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/23
AB  - A simple and efficient method for the preparation of secondary N-alkylarylamines via reductive amination of ketones with primary aromatic amines using activated zinc/acetic acid is described. It requires only equimolar amounts of the starting compounds and affords good yields of the corresponding amines (50-90%). It is not applicable to aldehydes nor aliphatic amines.
T2  - Synthesis, Stuttgart
T1  - A simple method for preparation of secondary aromatic amines
IS  - 11
SP  - 1043
EP  - 1045
DO  - 10.1055/s-1991-26642
ER  - 

@article{
author = "Mićović, Ivan V. and Ivanović, Milovan and Piatak, David M. and Bojić, Vera D.",
year = "1991",
abstract = "A simple and efficient method for the preparation of secondary N-alkylarylamines via reductive amination of ketones with primary aromatic amines using activated zinc/acetic acid is described. It requires only equimolar amounts of the starting compounds and affords good yields of the corresponding amines (50-90%). It is not applicable to aldehydes nor aliphatic amines.",
journal = "Synthesis, Stuttgart",
title = "A simple method for preparation of secondary aromatic amines",
number = "11",
pages = "1043-1045",
doi = "10.1055/s-1991-26642"
}

Mićović, I. V., Ivanović, M., Piatak, D. M.,& Bojić, V. D.. (1991). A simple method for preparation of secondary aromatic amines. in Synthesis, Stuttgart(11), 1043-1045.
https://doi.org/10.1055/s-1991-26642

Mićović IV, Ivanović M, Piatak DM, Bojić VD. A simple method for preparation of secondary aromatic amines. in Synthesis, Stuttgart. 1991;(11):1043-1045.
doi:10.1055/s-1991-26642 .

Mićović, Ivan V., Ivanović, Milovan, Piatak, David M., Bojić, Vera D., "A simple method for preparation of secondary aromatic amines" in Synthesis, Stuttgart, no. 11 (1991):1043-1045,
https://doi.org/10.1055/s-1991-26642 . .

TY  - JOUR
AU  - Mićović, Ivan V.
AU  - Ivanović, Milovan
AU  - Piatak, David M.
PY  - 1990
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/16
T2  - Synthesis, Stuttgart
T1  - Simplified preparation of 16-dehydropregnenolone acetate
IS  - 7
SP  - 591
EP  - 592
UR  - https://hdl.handle.net/21.15107/rcub_cherry_16
ER  - 

@article{
author = "Mićović, Ivan V. and Ivanović, Milovan and Piatak, David M.",
year = "1990",
journal = "Synthesis, Stuttgart",
title = "Simplified preparation of 16-dehydropregnenolone acetate",
number = "7",
pages = "591-592",
url = "https://hdl.handle.net/21.15107/rcub_cherry_16"
}

Mićović, I. V., Ivanović, M.,& Piatak, D. M.. (1990). Simplified preparation of 16-dehydropregnenolone acetate. in Synthesis, Stuttgart(7), 591-592.
https://hdl.handle.net/21.15107/rcub_cherry_16

Mićović IV, Ivanović M, Piatak DM. Simplified preparation of 16-dehydropregnenolone acetate. in Synthesis, Stuttgart. 1990;(7):591-592.
https://hdl.handle.net/21.15107/rcub_cherry_16 .

Mićović, Ivan V., Ivanović, Milovan, Piatak, David M., "Simplified preparation of 16-dehydropregnenolone acetate" in Synthesis, Stuttgart, no. 7 (1990):591-592,
https://hdl.handle.net/21.15107/rcub_cherry_16 .