【结 构 式】 |
【药物名称】YM17E 【化学名称】1,3-Bis[1-cycloheptyl-3-[4-(dimethylamino)phenyl]ureidomethyl]benzene dihydrochloride 【CA登记号】124884-99-7, 124900-72-7 (free base) 【 分 子 式 】C40H58Cl2N6O2 【 分 子 量 】725.85326 |
【开发单位】Yamanouchi (Originator) 【药理作用】Lipoprotein Disorders, Treatment of , METABOLIC DRUGS, ACAT Inhibitors |
合成路线1
Reaction of isophthaloyl dichloride (I) with cycloheptylamine (II) in the presence of triethylamine in dichloromethane gives N,N'-dicycloheptylisophthalimide (III), which is reduced with sodium bis(2-methoxyethoxy)aluminum hydride in toluene to yield 1,3-bis(cycloheptylaminomethyl)benzene (IV). Compound (IV) is treated with p-nitrophenylisocyanate (V) to afford 1,3-bis[1-cycloheptyl-3-(4-nitrophenyl)ureidomethyl]benzene (VI), which is reduced with hydrogen in the presence of palladium over charcoal to give 1,3-bis[1-cycloheptyl-3-(4-aminophenyl)ureidomethyl]benzene (VII). Finally, compound (VII) is treated with aqueous formaldehyde and hydrogen in the presence of platinum oxide in ethanol, followed by addition of hydrochloric acid in ethanol.
【1】 Ito, N.; Yasunaga, T.; Iizumi, Y.; Araki, T. (Yamanouchi Pharmaceutical Co., Ltd.); Diurea derivatives useful as medicaments and processes for the preparation thereof. AU 8928669; EP 0325397; JP 1990117651; US 5091419; US 5166429; US 5384425 . |
【2】 Yasunaga, T.; Araki, T.; Iwaoka, K.; Iizumi, Y.; Ohata, I.; Matsuda, K.; Ito, N.; Synthesis and activity of a novel phenylenediurea derivative with hypolipidemic and antiatherosclerotic activity. 111th Annu Meet Pharmaceut Soc Jpn (March 28-30, Tokyo) 1991, Abst 29V 3-040.. |
【3】 Graul, A.; Castaner, J.; Prous, J.; YM17E. Drugs Fut 1993, 18, 9, 813. |
【4】 Iizumi, Y.; Ohhata, I.; Iwaoka, K.; Matsuda, K.; Ito, N.; Yasunaga, T.; Araki, T.; Synthesis and hypocholesterolemic activity of phenylene and pyridylene diurea derivatives as ACAT inhibitors. 202nd ACS Natl Meet (Aug 25-30, New York) 1991, Abst MEDI 109. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 12501 | Isophthaloyl dichloride | 99-63-8 | C8H4Cl2O2 | 详情 | 详情 |
(II) | 11926 | 1-[4-(Chloromethyl)-2-hydroxy-3-propylphenyl]-1-ethanone | C12H15ClO2 | 详情 | 详情 | |
(III) | 14907 | N(1),N(3)-dicycloheptylisophthalamide | C22H32N2O2 | 详情 | 详情 | |
(IV) | 14908 | N-cycloheptyl-N-[3-[(cycloheptylamino)methyl]benzyl]amine; N-[3-[(cycloheptylamino)methyl]benzyl]cycloheptanamine | C22H36N2 | 详情 | 详情 | |
(V) | 14909 | 1-isocyanato-4-nitrobenzene; 4-Nitrophenyl isocyanate | 100-28-7 | C7H4N2O3 | 详情 | 详情 |
(VI) | 14910 | N-cycloheptyl-N-[3-([cycloheptyl[(4-nitroanilino)carbonyl]amino]methyl)benzyl]-N'-(4-nitrophenyl)urea | C36H44N6O6 | 详情 | 详情 | |
(VII) | 14911 | N-(3-[[[(4-aminoanilino)carbonyl](cycloheptyl)amino]methyl]benzyl)-N'-(4-aminophenyl)-N-cycloheptylurea | C36H48N6O2 | 详情 | 详情 |