TY  - JOUR
AU  - Jovanović, Miloš
AU  - Jovanović, Predrag
AU  - Tasić, Gordana
AU  - Simić, Milena R.
AU  - Maslak, Veselin
AU  - Rakić, Srđan
AU  - Rodić, Marko
AU  - Vlahović, Filip
AU  - Petković, Miloš
AU  - Savić, Vladimir
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/7166
AB  - Enallenylamideshave been utilizedforthe synthesisof heterobicycle[4.2.0]octanederiva-tives via Ir/hν promoted[2+2] cycloadditionreaction.The reactionspecificallytargets the distaldoublebond of the allene moiety, and resultsin theexclusiveformationof thetransproduct.Theprocessis conductedat room temperatureand underan inert atmosphere.An extensivestudy on thesubstituentpropensitiesduringthe cycloadditionstep revealedvariableeffects.Electron-withdrawinggroupsconjugatedwith the doublebond participat-ing in the cycloadditioneither hinderedthe processor reducedits yield. Conversely, electron-donatingsubstituentsenhancedthe efficiency, resultinginproductyields rangingfrom 60% to 88%. Our studyalso demonstratedthe influenceof protectinggroupson the reactionpathway.
PB  - John Wiley and Sons Inc
T2  - Advanced Synthesis and Catalysis
T1  - Regio‐ and Stereoselective, Intramolecular [2+2] Cycloaddition of Allenes, Promoted by Visible Light Photocatalysis
VL  - 365
IS  - 15
SP  - 2516
EP  - 2523
DO  - 10.1002/adsc.202300301
ER  - 

@article{
author = "Jovanović, Miloš and Jovanović, Predrag and Tasić, Gordana and Simić, Milena R. and Maslak, Veselin and Rakić, Srđan and Rodić, Marko and Vlahović, Filip and Petković, Miloš and Savić, Vladimir",
year = "2023",
abstract = "Enallenylamideshave been utilizedforthe synthesisof heterobicycle[4.2.0]octanederiva-tives via Ir/hν promoted[2+2] cycloadditionreaction.The reactionspecificallytargets the distaldoublebond of the allene moiety, and resultsin theexclusiveformationof thetransproduct.Theprocessis conductedat room temperatureand underan inert atmosphere.An extensivestudy on thesubstituentpropensitiesduringthe cycloadditionstep revealedvariableeffects.Electron-withdrawinggroupsconjugatedwith the doublebond participat-ing in the cycloadditioneither hinderedthe processor reducedits yield. Conversely, electron-donatingsubstituentsenhancedthe efficiency, resultinginproductyields rangingfrom 60% to 88%. Our studyalso demonstratedthe influenceof protectinggroupson the reactionpathway.",
publisher = "John Wiley and Sons Inc",
journal = "Advanced Synthesis and Catalysis",
title = "Regio‐ and Stereoselective, Intramolecular [2+2] Cycloaddition of Allenes, Promoted by Visible Light Photocatalysis",
volume = "365",
number = "15",
pages = "2516-2523",
doi = "10.1002/adsc.202300301"
}

Jovanović, M., Jovanović, P., Tasić, G., Simić, M. R., Maslak, V., Rakić, S., Rodić, M., Vlahović, F., Petković, M.,& Savić, V.. (2023). Regio‐ and Stereoselective, Intramolecular [2+2] Cycloaddition of Allenes, Promoted by Visible Light Photocatalysis. in Advanced Synthesis and Catalysis
John Wiley and Sons Inc., 365(15), 2516-2523.
https://doi.org/10.1002/adsc.202300301

Jovanović M, Jovanović P, Tasić G, Simić MR, Maslak V, Rakić S, Rodić M, Vlahović F, Petković M, Savić V. Regio‐ and Stereoselective, Intramolecular [2+2] Cycloaddition of Allenes, Promoted by Visible Light Photocatalysis. in Advanced Synthesis and Catalysis. 2023;365(15):2516-2523.
doi:10.1002/adsc.202300301 .

Jovanović, Miloš, Jovanović, Predrag, Tasić, Gordana, Simić, Milena R., Maslak, Veselin, Rakić, Srđan, Rodić, Marko, Vlahović, Filip, Petković, Miloš, Savić, Vladimir, "Regio‐ and Stereoselective, Intramolecular [2+2] Cycloaddition of Allenes, Promoted by Visible Light Photocatalysis" in Advanced Synthesis and Catalysis, 365, no. 15 (2023):2516-2523,
https://doi.org/10.1002/adsc.202300301 . .

TY  - JOUR
AU  - Mitrović, Jelena
AU  - Divović-Matović, Branka
AU  - Knutson, Daniel E.
AU  - Petković, Miloš
AU  - Đorović, Đordje
AU  - Randjelović, Danijela
AU  - Dobričić, Vladimir D.
AU  - Đoković, Jelena B.
AU  - Lunter, Dominique J.
AU  - Cook, James M.
AU  - Savić, Miroslav M.
AU  - Savić, Snežana D.
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5665
AB  - Preclinical development of deuterated pyrazoloquinolinone ligands, promising drug candidates for various neuropsychiatric disorders, was hindered by unusually low solubility in water and oils. DK-I-60-3 (7-methoxy-d3-2-(4-methoxy-d3-phenyl)-2,5-dihydro-3Hpyrazolo[4,3-c]quinolin-3-one) is one of such pyrazoloquinolinones, and we recently reported about increased oral bioavailability of its nanocrystal formulation (NC). Lipid nanoparticles (LNP) with a high concentration of lecithin, which enhances loading capacity of the lipid matrix, may give rise to further improvement. After preformulation studies by differential scanning calorimetry and polarized light microscopy, LNP were prepared by the hot high pressure homogenization, and characterized in terms of particle size, morphology, and encapsulation efficacy. The layered structure visible on atomic force micrographs was confirmed by nuclear magnetic resonance. Obtained formulations were desirably stable, with small particle size (<100 nm), and high encapsulation efficacy (>99 %). Lecithin was partially fluid and most probably located in the outer shell of the particle, together with DK-I-60-3. While the hydrophobic part of polysorbate 80 was completely immobilized, its hydrophilic part was free in the aqueous phase. In oral neuropharmacokinetic study in rats, an around 1.5-fold increase of area under the curve with LNP compared to NC was noticed both in brain and plasma. In bioavailability study, F value of LNP (34.7 ± 12.4 %) was 1.4-fold higher than of NC (24.5 ± 7.8 %); however, this difference did not reach statistical significance. Therefore, employment of LNP platform in preclinical formulation of DK-I-60-3 imparted an incremental improvement of its physicochemical as well as pharmacokinetic behavior.
PB  - Elsevier B.V.
T2  - International Journal of Pharmaceutics
T1  - High amount of lecithin facilitates oral delivery of a poorly soluble pyrazoloquinolinone ligand formulated in lipid nanoparticles: Physicochemical, structural and pharmacokinetic performances
VL  - 633
SP  - 122613
DO  - 10.1016/j.ijpharm.2023.122613
ER  - 

@article{
author = "Mitrović, Jelena and Divović-Matović, Branka and Knutson, Daniel E. and Petković, Miloš and Đorović, Đordje and Randjelović, Danijela and Dobričić, Vladimir D. and Đoković, Jelena B. and Lunter, Dominique J. and Cook, James M. and Savić, Miroslav M. and Savić, Snežana D.",
year = "2023",
abstract = "Preclinical development of deuterated pyrazoloquinolinone ligands, promising drug candidates for various neuropsychiatric disorders, was hindered by unusually low solubility in water and oils. DK-I-60-3 (7-methoxy-d3-2-(4-methoxy-d3-phenyl)-2,5-dihydro-3Hpyrazolo[4,3-c]quinolin-3-one) is one of such pyrazoloquinolinones, and we recently reported about increased oral bioavailability of its nanocrystal formulation (NC). Lipid nanoparticles (LNP) with a high concentration of lecithin, which enhances loading capacity of the lipid matrix, may give rise to further improvement. After preformulation studies by differential scanning calorimetry and polarized light microscopy, LNP were prepared by the hot high pressure homogenization, and characterized in terms of particle size, morphology, and encapsulation efficacy. The layered structure visible on atomic force micrographs was confirmed by nuclear magnetic resonance. Obtained formulations were desirably stable, with small particle size (<100 nm), and high encapsulation efficacy (>99 %). Lecithin was partially fluid and most probably located in the outer shell of the particle, together with DK-I-60-3. While the hydrophobic part of polysorbate 80 was completely immobilized, its hydrophilic part was free in the aqueous phase. In oral neuropharmacokinetic study in rats, an around 1.5-fold increase of area under the curve with LNP compared to NC was noticed both in brain and plasma. In bioavailability study, F value of LNP (34.7 ± 12.4 %) was 1.4-fold higher than of NC (24.5 ± 7.8 %); however, this difference did not reach statistical significance. Therefore, employment of LNP platform in preclinical formulation of DK-I-60-3 imparted an incremental improvement of its physicochemical as well as pharmacokinetic behavior.",
publisher = "Elsevier B.V.",
journal = "International Journal of Pharmaceutics",
title = "High amount of lecithin facilitates oral delivery of a poorly soluble pyrazoloquinolinone ligand formulated in lipid nanoparticles: Physicochemical, structural and pharmacokinetic performances",
volume = "633",
pages = "122613",
doi = "10.1016/j.ijpharm.2023.122613"
}

Mitrović, J., Divović-Matović, B., Knutson, D. E., Petković, M., Đorović, Đ., Randjelović, D., Dobričić, V. D., Đoković, J. B., Lunter, D. J., Cook, J. M., Savić, M. M.,& Savić, S. D.. (2023). High amount of lecithin facilitates oral delivery of a poorly soluble pyrazoloquinolinone ligand formulated in lipid nanoparticles: Physicochemical, structural and pharmacokinetic performances. in International Journal of Pharmaceutics
Elsevier B.V.., 633, 122613.
https://doi.org/10.1016/j.ijpharm.2023.122613

Mitrović J, Divović-Matović B, Knutson DE, Petković M, Đorović Đ, Randjelović D, Dobričić VD, Đoković JB, Lunter DJ, Cook JM, Savić MM, Savić SD. High amount of lecithin facilitates oral delivery of a poorly soluble pyrazoloquinolinone ligand formulated in lipid nanoparticles: Physicochemical, structural and pharmacokinetic performances. in International Journal of Pharmaceutics. 2023;633:122613.
doi:10.1016/j.ijpharm.2023.122613 .

Mitrović, Jelena, Divović-Matović, Branka, Knutson, Daniel E., Petković, Miloš, Đorović, Đordje, Randjelović, Danijela, Dobričić, Vladimir D., Đoković, Jelena B., Lunter, Dominique J., Cook, James M., Savić, Miroslav M., Savić, Snežana D., "High amount of lecithin facilitates oral delivery of a poorly soluble pyrazoloquinolinone ligand formulated in lipid nanoparticles: Physicochemical, structural and pharmacokinetic performances" in International Journal of Pharmaceutics, 633 (2023):122613,
https://doi.org/10.1016/j.ijpharm.2023.122613 . .