Properties and synthesis of milrinone
Milrinon svojstva i sinteza
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Milrinone, 1,6-dihydro-2-methyl-6-oxo-(3,4’-bipyridine)-5-carbonitrile, is a positive inotropic cardiotonic agent with vasodilator properties that acts as selective phosphodiesterase 3 inhibitor in cardiac and vascular smooth muscle. Trade names of milrinone are Primacor, Corotrop, Corotrope, and Milrila. Milrinone, an amrinone derivative, is 20 to 50 times more active than amrinone and possesses reduced propensity to side effects. The use of milrinone has created controversy in the medical as the result of increased mortality rate among patients that received high amounts of milrinone in oral form. Research show that it can be beneficial for patients with severe congestive heart failure when used as short-time intravenous therapy. Milrinone properties, stability, as well as mechanism of action and synthesis under laboratory and industry conditions have been described in this paper. For industrial purposes milrinone is synthesized by condensation of cyanoacetamide with 4-(dimethylamino...)-3-(4-pyridinyl)-3-buten-2-one and 4-ethoxy-3-(4-pyridinyl)-3-buten-2-one in presence of a base, or by the reaction of 1-(4-pyridinyl)-2-propanone with ethoxymethylenmalononitrile or 4-alkoxy-3-(4-pyridinyl)-3-buten-2-one with malononitrile without the use of external base. The starting compound for these syntheses is 4-picoline. Alternative synthesis of milrinone starts from 2-methyl-3-(4-pyridylidiene)-1,1,5-tricyano-1,4pentadiene-5-carboxamide and 2-methyl-6-oxo-1,6-dihydro-3,4’-bipyridine-5-carboxamide. Lastly, methods for milrinone synthesis in laboratory, injection preparation and purification have been summarized.
Milrinon (Primacor®, Corotrop®, Corotrope® ili Milrila®) pripada grupi bipiridinskih kardiotonika i vazodilatatora koji selektivno inhibiraju enzim fosfodiesterazu 3 (PDE-3). Primenjuje se u terapiji kongestivne srčane insuficijencije dugi niz godina. Mirlinon hemijski predstavlja 1,6-dihidro-2-metil-6-okso-(3,4’-bipiridin)-5-karbonitril-laktat. U literaturi postoje podaci o mogućem letalnom ishodu prilikom dugotrajne oralne primene ovog leka, zbog čega se daje intravenski, u kratkom vremenskom periodu. U radu je, na osnovu literaturnih podataka, dat pregled osnovnih svojstava, mehanizam delovanja i stabilnost milrinona, kao i načini za njegovo laboratorijsko i industrijsko dobijanje. Na kraju je dat način prečišćavanja kao i postupak izrade injekcija.
Ključne reči:
Milrinone / Properties / Mechanism of action / Synthesis / milrinon / svojstva / mehanizam delovanja / sintezaIzvor:
Hemijska industrija, 2013, 67, 1, 17-25Izdavač:
- Association of Chemical Engineers of Serbia
Finansiranje / projekti:
- Proučavanje sinteze, strukture i aktivnosti organskih jedinjenja prirodnog i sintetskog porekla (RS-MESTD-Basic Research (BR or ON)-172013)
DOI: 10.2298/HEMIND120410057M
ISSN: 0367-598X
WoS: 000317808000002
Scopus: 2-s2.0-84875044167
Institucija/grupa
Tehnološko-metalurški fakultetTY - JOUR AU - Mirković, Jelena M. AU - Mijin, Dušan AU - Petrović, Slobodan PY - 2013 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/2376 AB - Milrinone, 1,6-dihydro-2-methyl-6-oxo-(3,4’-bipyridine)-5-carbonitrile, is a positive inotropic cardiotonic agent with vasodilator properties that acts as selective phosphodiesterase 3 inhibitor in cardiac and vascular smooth muscle. Trade names of milrinone are Primacor, Corotrop, Corotrope, and Milrila. Milrinone, an amrinone derivative, is 20 to 50 times more active than amrinone and possesses reduced propensity to side effects. The use of milrinone has created controversy in the medical as the result of increased mortality rate among patients that received high amounts of milrinone in oral form. Research show that it can be beneficial for patients with severe congestive heart failure when used as short-time intravenous therapy. Milrinone properties, stability, as well as mechanism of action and synthesis under laboratory and industry conditions have been described in this paper. For industrial purposes milrinone is synthesized by condensation of cyanoacetamide with 4-(dimethylamino)-3-(4-pyridinyl)-3-buten-2-one and 4-ethoxy-3-(4-pyridinyl)-3-buten-2-one in presence of a base, or by the reaction of 1-(4-pyridinyl)-2-propanone with ethoxymethylenmalononitrile or 4-alkoxy-3-(4-pyridinyl)-3-buten-2-one with malononitrile without the use of external base. The starting compound for these syntheses is 4-picoline. Alternative synthesis of milrinone starts from 2-methyl-3-(4-pyridylidiene)-1,1,5-tricyano-1,4pentadiene-5-carboxamide and 2-methyl-6-oxo-1,6-dihydro-3,4’-bipyridine-5-carboxamide. Lastly, methods for milrinone synthesis in laboratory, injection preparation and purification have been summarized. AB - Milrinon (Primacor®, Corotrop®, Corotrope® ili Milrila®) pripada grupi bipiridinskih kardiotonika i vazodilatatora koji selektivno inhibiraju enzim fosfodiesterazu 3 (PDE-3). Primenjuje se u terapiji kongestivne srčane insuficijencije dugi niz godina. Mirlinon hemijski predstavlja 1,6-dihidro-2-metil-6-okso-(3,4’-bipiridin)-5-karbonitril-laktat. U literaturi postoje podaci o mogućem letalnom ishodu prilikom dugotrajne oralne primene ovog leka, zbog čega se daje intravenski, u kratkom vremenskom periodu. U radu je, na osnovu literaturnih podataka, dat pregled osnovnih svojstava, mehanizam delovanja i stabilnost milrinona, kao i načini za njegovo laboratorijsko i industrijsko dobijanje. Na kraju je dat način prečišćavanja kao i postupak izrade injekcija. PB - Association of Chemical Engineers of Serbia T2 - Hemijska industrija T1 - Properties and synthesis of milrinone T1 - Milrinon svojstva i sinteza EP - 25 IS - 1 SP - 17 VL - 67 DO - 10.2298/HEMIND120410057M ER -
@article{ author = "Mirković, Jelena M. and Mijin, Dušan and Petrović, Slobodan", year = "2013", abstract = "Milrinone, 1,6-dihydro-2-methyl-6-oxo-(3,4’-bipyridine)-5-carbonitrile, is a positive inotropic cardiotonic agent with vasodilator properties that acts as selective phosphodiesterase 3 inhibitor in cardiac and vascular smooth muscle. Trade names of milrinone are Primacor, Corotrop, Corotrope, and Milrila. Milrinone, an amrinone derivative, is 20 to 50 times more active than amrinone and possesses reduced propensity to side effects. The use of milrinone has created controversy in the medical as the result of increased mortality rate among patients that received high amounts of milrinone in oral form. Research show that it can be beneficial for patients with severe congestive heart failure when used as short-time intravenous therapy. Milrinone properties, stability, as well as mechanism of action and synthesis under laboratory and industry conditions have been described in this paper. For industrial purposes milrinone is synthesized by condensation of cyanoacetamide with 4-(dimethylamino)-3-(4-pyridinyl)-3-buten-2-one and 4-ethoxy-3-(4-pyridinyl)-3-buten-2-one in presence of a base, or by the reaction of 1-(4-pyridinyl)-2-propanone with ethoxymethylenmalononitrile or 4-alkoxy-3-(4-pyridinyl)-3-buten-2-one with malononitrile without the use of external base. The starting compound for these syntheses is 4-picoline. Alternative synthesis of milrinone starts from 2-methyl-3-(4-pyridylidiene)-1,1,5-tricyano-1,4pentadiene-5-carboxamide and 2-methyl-6-oxo-1,6-dihydro-3,4’-bipyridine-5-carboxamide. Lastly, methods for milrinone synthesis in laboratory, injection preparation and purification have been summarized., Milrinon (Primacor®, Corotrop®, Corotrope® ili Milrila®) pripada grupi bipiridinskih kardiotonika i vazodilatatora koji selektivno inhibiraju enzim fosfodiesterazu 3 (PDE-3). Primenjuje se u terapiji kongestivne srčane insuficijencije dugi niz godina. Mirlinon hemijski predstavlja 1,6-dihidro-2-metil-6-okso-(3,4’-bipiridin)-5-karbonitril-laktat. U literaturi postoje podaci o mogućem letalnom ishodu prilikom dugotrajne oralne primene ovog leka, zbog čega se daje intravenski, u kratkom vremenskom periodu. U radu je, na osnovu literaturnih podataka, dat pregled osnovnih svojstava, mehanizam delovanja i stabilnost milrinona, kao i načini za njegovo laboratorijsko i industrijsko dobijanje. Na kraju je dat način prečišćavanja kao i postupak izrade injekcija.", publisher = "Association of Chemical Engineers of Serbia", journal = "Hemijska industrija", title = "Properties and synthesis of milrinone, Milrinon svojstva i sinteza", pages = "25-17", number = "1", volume = "67", doi = "10.2298/HEMIND120410057M" }
Mirković, J. M., Mijin, D.,& Petrović, S.. (2013). Properties and synthesis of milrinone. in Hemijska industrija Association of Chemical Engineers of Serbia., 67(1), 17-25. https://doi.org/10.2298/HEMIND120410057M
Mirković JM, Mijin D, Petrović S. Properties and synthesis of milrinone. in Hemijska industrija. 2013;67(1):17-25. doi:10.2298/HEMIND120410057M .
Mirković, Jelena M., Mijin, Dušan, Petrović, Slobodan, "Properties and synthesis of milrinone" in Hemijska industrija, 67, no. 1 (2013):17-25, https://doi.org/10.2298/HEMIND120410057M . .