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【结 构 式】 
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【药物名称】COR-32-24, COR-3224 【化学名称】2-Amino-5-(4-phenylpiperazin-1-ylmethyl)-2-oxazoline 【CA登记号】91595-86-7 【 分 子 式 】C14H20N4O 【 分 子 量 】260.3417 |
【开发单位】Cortial (Originator), Sarget (Licensee) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS |
合成路线1
The reaction of phenylpiperazine (I) with epichlorhydrin (II) leads to 1-chloro-3-(1-phenyl-4-piperazinyl)-2-propanol. This intermediate is dehydrohalogenated to 1-(1-phenyl-4-piperazinyl)-2,3-epoxypropane (III) using sodium hydroxide. The epoxide is converted without further purification into the corresponding 4,5-dihydro-5-[(4-phenyl-1-piperazinyl)methyl]-2-oxazolamine (COR3224) by condensation with monosodium cyanamide salt in methanol, which permits the solubilization of all compounds. The amidine group of the oxazoline ring induces a tautomeric amino-imino equilibrium. For COR3224 it has been shown by X-ray crystallography that the amino form is preponderant in the free base, whereas the imino form predominates in salts.
| 【1】 Creuzet, M.-H.; Feniou, C.; Jarry, C.; Prat, G.; Pontagnier, H. (Societé Cortial SA); Novel 2-amino-5-aminomethyl-2-oxazolines. EP 0106776; FR 2546167 . |
| 【2】 D'Arnoux, C.; Panconi, E.; Descas, P.; Vaugien, B.; Lambrey, B.; Mosser, J.; Jarry, C.; Gomond, P.; Saudubray, F.; Roux, J.; COR3224. Drugs Fut 1991, 16, 10, 893. |
| 【3】 Ouhabi, J.; Jarry, C.; Bosc, J.J.; Carpy, A.; Crystal and molecular structure of 5-(1-aryl-4-piperazino)-methyl-2-amino-2-oxazolines with antidepressant activity. Arch Pharm 1990, 323, 157-61. |
| 【4】 Bosc, J.J.; Descas, P.; Carpy, A.; Panconi, E.; Jarry, C.; Synthesis and antidepressant activity of 5-(1-aryl-4-piperazino)methyl-2-amino-2-oxazolines. Eur J Med Chem 1992, 27, 5, 437. |