- Synthesis method of levosimendan drug intermediate p-acetaminophenylethylketone
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The invention relates to a synthesis method of a levosimendan drug intermediate p-acetaminophenylethylketone, which comprises the following steps: adding 430-460ml of cyclohexane into a 1.5L reaction vessel which is provided with a stirrer, a reflux condenser and a thermometer, cooling the solution to 6-9 DEG C, slowly adding 2.9-3.1 mol of stannous chloride, refluxing for 80-120 minutes, and adding 1.0 mol of acetanilide in batches within 2-3 hours; after finishing addition, continuing reacting for 60-90 minutes, and adding 110ml of propanamide under reflux conditions within 3-4 hours; and after finishing addition, continuing refluxing for 5 hours until the solution becomes dark, distilling to remove the cyclohexane, heating the solution to 85-90 DEG C, reacting for 3-4 hours, adding the reaction product into 2.3L of oxalic acid solution, controlling the stirring rate at 160-190 rpm, precipitating a solid, filtering, washing the solid with a salt solution, washing with triethylamine, dehydrating with a dehydrating agent, and recrystallizing in propionitrile to obtain the p-acetaminophenylethylketone.
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Paragraph 0015; 0016
(2016/11/21)
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- (±)-2-(N-tert-Butylamino)-3′-[125I]-iodo-4′- azidopropiophenone: A dopamine transporter and nicotinic acetylcholine receptor photoaffinity ligand based on bupropion (Wellbutrin, Zyban)
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Towards addressing the knowledge gap of how bupropion interacts with the dopamine transporter (DAT) and nicotinic acetylcholine receptors (nAChRs), a ligand was synthesized in which the chlorine of bupropion was isosterically replaced with an iodine and a photoreactive azide was added to the 4′-position of the aromatic ring. Analog (±)-3 (SADU-3-72) demonstrated modest DAT and α4β2 nAChR affinity. A radioiodinated version was shown to bind covalently to hDAT expressed in cultured cells and affinity-purified, lipid-reincorporated human α4β2 neuronal nAChRs. Co-incubation of (±)-[125I]-3 with non-radioactive (±)-bupropion or (-)-cocaine blocked labeling of these proteins. Compound (±)-[125I]-3 represents the first successful example of a DAT and nAChR photoaffinity ligand based on the bupropion scaffold. Such ligands are expected to assist in mapping bupropion-binding pockets within plasma membrane monoamine transporters and ligand-gated nAChR ion channels.
- Lapinsky, David J.,Aggarwal, Shaili,Nolan, Tammy L.,Surratt, Christopher K.,Lever, John R.,Acharya, Rejwi,Vaughan, Roxanne A.,Pandhare, Akash,Blanton, Michael P.
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supporting information; experimental part
p. 523 - 526
(2012/03/26)
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- Synthesis and anti-congestive heart failure activity of novel levosimendan analogues
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A series of levosimendan analogues were designed and synthesized, employing the Friedel-Crafts reaction, hydrolysis, and cyclization from the key intermediate compound R(-)-6-(4-aminophenyl)-5-methyl-4, 5-dihydro-3(2H)- pyridazinone, which was obtained from the starting material, acetanilide. These compounds, except 1b, exhibited potent anti-congestive heart failure activities, especially the compounds 1e and 1k, which showed more effective action than levosimendan. Springer Science+Business Media, LLC 2010.
- Wang, Lisheng,Zhou, Hongxiang,Yang, Bin,Chen, Zhigang,Yang, Hua
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experimental part
p. 287 - 292
(2012/06/05)
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- NOVEL BENZIMIDAZOLEDIHYDROTHIADIAZINONE DERIVATIVES AS FRUCTOSE-1,6-BISPHOSPHATASE INHIBITORS, AND PHARMACEUTICAL COMPOSITIONS COMPRISING SAME
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The present invention relates to novel benzimidazole-dihydrothiadiazinone derivatives as fructose-1,6-bisphosphatase inhibitors, to processes for the preparation thereof and to the use thereof in therapy, especially for the treatment of diabetes.
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Page/Page column 34
(2010/12/29)
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- NOVEL BENZIMIDAZOLEDIHYDROTHIADIAZINONE DERIVATIVES AS FRUCTOSE-1,6-BISPHOSPHATASE INHIBITORS, AND PHARMACEUTICAL COMPOSITIONS COMPRISING SAME
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The present invention relates to novel benzimidazole-dihydrothiadiazinone derivatives as fructose-1,6-bisphosphatase inhibitors, to processes for the preparation thereof and to the use thereof in therapy, especially for the treatment of diabetes.
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Page/Page column 74
(2009/06/27)
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- Chemical process
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This invention relates to a Friedel-Crafts acylation process using trichlorobenzene as solvent.
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