发明公开
- 专利标题: Medical application of lipid derivatives of dopamine
- 专利标题(中): 医药用多巴胺的脂质衍生物
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申请号: EP10191670.8申请日: 2010-11-18
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公开(公告)号: EP2324824A3公开(公告)日: 2011-06-15
- 发明人: Pokorski, Mieczyslaw , Rekawek,, Agnieszka , Zajac,, Dominika , Czarnocki,, Zbigniew , Przegalinski,, Edmund , Konieczny,, Jolanta , Roszkowski, Piotr
- 申请人: Instytut Medycyny Doswiadczalnej I Klinicznej , Uniwersytet Warszawski , Instytut Farmakologii PAN
- 申请人地址: im.M. Mossakowskiego, PAN, ul. Pawinskiego 5a Warszawa 02-106 PL
- 专利权人: Instytut Medycyny Doswiadczalnej I Klinicznej,Uniwersytet Warszawski,Instytut Farmakologii PAN
- 当前专利权人: Instytut Medycyny Doswiadczalnej I Klinicznej,Uniwersytet Warszawski,Instytut Farmakologii PAN
- 当前专利权人地址: im.M. Mossakowskiego, PAN, ul. Pawinskiego 5a Warszawa 02-106 PL
- 代理机构: Brodowska, Iwona
- 优先权: PL38962109 20091119
- 主分类号: A61K31/165
- IPC分类号: A61K31/165 ; A61P25/00 ; A61P25/16
摘要:
The subject of the present invention is the medical application of N-oleoyl-dopamine and 3'-O-methyl-N-oleoyl-dopamine for the production of a medication for treatment or prophylaxis of disturbances or states due to deficiency of dopamine, preferably chosen from the group covering oxygen deficiencies (hypoxia) in anesthetized and awake mammals, breathing with atmospheric oxygen (normoxia), for the respiratory responses to hypoxia in mammals, lack of dopamine binding to the membrane system in the mammalian brain, disturbances in metabolic pathways of dopamine metabolism, states of dopamine deficiencies provoked by morbid or genetic factors as well as under condition connected to the physiological process of aging of the organism, through the systemic introduction of the compound to the mammalian organism.
The subject of the present invention is also the method of production of 3'-O-methyl-N-oleoyl-dopamine in vitro which consists of, according to the present invention, a reaction of 3-O-methyl-dopamine hydrochloride with oleic acid in the presence of, preferably, BOP
(Benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate), DCC ( N , N '-dicyclohexylcarbodiimide), DMAP (4-Dimethylaminopyridine) and THF (tetrahydrofuran), CH 2 Cl 2 (dichloromethane), CHCl 3 (chloroform), toluene, diethyl ether. The reaction mixture is cooled to temperature of 0-10°C, a solution of trietanolamine is added under continuous stirring and
3'-O-methyl-N-oleoyl-dopamine is precipitated and purified by a known method.
A variant of the method of production of 3'-O-methyl-N-oleoyl-dopamie consists of, according to the present invention, a reaction of methylation of N-oleoyl-dopamine by the catechol-O-methyltransferase (COMT) in the presence of
S-adenosyl-L-methionine (SAM) and magnesium ions in phosphate buffered saline (PBS) solution buffered to pH of 7.0-8.0 at temperature of 25-45°C, followed by the precipitation and purification of 3'-O-methyl-N-oleoyl-dopamine by a known method.
The subject of the present invention is also the method of production of 3'-O-methyl-N-oleoyl-dopamine in vitro which consists of, according to the present invention, a reaction of 3-O-methyl-dopamine hydrochloride with oleic acid in the presence of, preferably, BOP
(Benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate), DCC ( N , N '-dicyclohexylcarbodiimide), DMAP (4-Dimethylaminopyridine) and THF (tetrahydrofuran), CH 2 Cl 2 (dichloromethane), CHCl 3 (chloroform), toluene, diethyl ether. The reaction mixture is cooled to temperature of 0-10°C, a solution of trietanolamine is added under continuous stirring and
3'-O-methyl-N-oleoyl-dopamine is precipitated and purified by a known method.
A variant of the method of production of 3'-O-methyl-N-oleoyl-dopamie consists of, according to the present invention, a reaction of methylation of N-oleoyl-dopamine by the catechol-O-methyltransferase (COMT) in the presence of
S-adenosyl-L-methionine (SAM) and magnesium ions in phosphate buffered saline (PBS) solution buffered to pH of 7.0-8.0 at temperature of 25-45°C, followed by the precipitation and purification of 3'-O-methyl-N-oleoyl-dopamine by a known method.
公开/授权文献
- EP2324824B1 Medical application of a lipid derivative of dopamine 公开/授权日:2014-06-18
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