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【结 构 式】 
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【药物名称】T-0970 【化学名称】N'-(3-tert-Butyl-2-hydroxy-5-methoxyphenyl)-N-(3-pyridyl)-N-(4-pyridylmethyl)urea triphosphate 【CA登记号】195313-54-3, 195313-53-2 (free base) 【 分 子 式 】C23H35N4O15P3 【 分 子 量 】700.4746 |
【开发单位】Tanabe Seiyaku (Originator) 【药理作用】CARDIOVASCULAR DRUGS, Cerebrovascular Diseases, Treatment of, GASTROINTESTINAL DRUGS, Liver and Biliary Tract Disorders, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Antioxidants, Free Radical Scavengers |
合成路线1
The intermediate secondary amine (IV) was prepared by condensation of 3-aminopyridine (I) with isonicotinic aldehyde (II), followed by catalytic hydrogenation of the resulting imine (III).
| 【1】 Kubota, H.; Suzumura, K.; Suzuki, T.; Ohmizu, H.; Kashimura, Y.; Antioxidative property of T-0970, a new ureidophenol derivative. Free Radical Research 2000, 32, 3, 255. |
| 【2】 Suzuki, T.; Ohmizu, H.; Hashimura, Y.; Kubota, H.; Tanaka, K. (Tanabe Seiyaku Co., Ltd.); Phenol-derivs. having pharmaceutical activity and process for preparing the same. EP 0790240; JP 1998195037; US 5849732 . |
| 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) | 33327 | 3-Pyridinylamine; 3-Aminopyridine; 3-Pyridinamine | 462-08-8 | C5H6N2 | 详情 | 详情 |
| (II) | 17203 | 4-Pyridinecarboxaldehyde; isonicotinaldehyde | 872-85-5 | C6H5NO | 详情 | 详情 |
| (III) | 41431 | N-[(Z)-4-pyridinylmethylidene]-3-pyridinamine; N-(3-pyridinyl)-N-[(Z)-4-pyridinylmethylidene]amine | C11H9N3 | 详情 | 详情 | |
| (IV) | 41432 | N-(3-pyridinyl)-N-(4-pyridinylmethyl)amine; N-(4-pyridinylmethyl)-3-pyridinamine | C11H11N3 | 详情 | 详情 |
合成路线2
The diazonium salt (VI), prepared by diazotization of p-anisidine (V), was added to 4-methoxy-2-tert-butylphenol (VII) yielding the azo adduct (VIII). Protection of the phenolic hydroxyl group of (VIII) was carried out by alkylation with methoxymethyl chloride and NaH to give methoxymethyl ether (IX). Then, reductive cleavage of the diazo group of (IX) by hydrogenation over Pd/C furnished aniline (X) (1). Subsequent reaction of (X) with triphosgene and triethylamine in cold CH2Cl2 produced isocyanate (XI), which was condensed with amine (IV) to afford urea (XII). After acid deprotection of the methoxymethyl group of (XII), treatment with phosphoric acid in EtOH provided the title triphosphate salt.
| 【1】 Kubota, H.; Suzumura, K.; Suzuki, T.; Ohmizu, H.; Kashimura, Y.; Antioxidative property of T-0970, a new ureidophenol derivative. Free Radical Research 2000, 32, 3, 255. |
| 【2】 Suzuki, T.; Ohmizu, H.; Hashimura, Y.; Kubota, H.; Tanaka, K. (Tanabe Seiyaku Co., Ltd.); Phenol-derivs. having pharmaceutical activity and process for preparing the same. EP 0790240; JP 1998195037; US 5849732 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 41432 | N-(3-pyridinyl)-N-(4-pyridinylmethyl)amine; N-(4-pyridinylmethyl)-3-pyridinamine | C11H11N3 | 详情 | 详情 | |
| (V) | 10478 | p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine | 104-94-9 | C7H9NO | 详情 | 详情 |
| (VI) | 41433 | 4-methoxybenzenediazonium | C7H7N2O | 详情 | 详情 | |
| (VII) | 40700 | 2-(tert-butyl)-4-methoxyphenol | C11H16O2 | 详情 | 详情 | |
| (VIII) | 40701 | 2-(tert-butyl)-4-methoxy-6-[(Z)-2-(4-methoxyphenyl)diazenyl]phenol | C18H22N2O3 | 详情 | 详情 | |
| (IX) | 40702 | (Z)-1-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-2-(4-methoxyphenyl)diazene; 3-(tert-butyl)-4-(methoxymethoxy)-5-[(Z)-2-(4-methoxyphenyl)diazenyl]phenyl methyl ether | C20H26N2O4 | 详情 | 详情 | |
| (X) | 40703 | 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenylamine; 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)aniline | C13H21NO3 | 详情 | 详情 | |
| (XI) | 41434 | 3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl isocyanate; 1-(tert-butyl)-3-isocyanato-5-methoxy-2-(methoxymethoxy)benzene | C14H19NO4 | 详情 | 详情 | |
| (XII) | 41435 | N'-[3-(tert-butyl)-5-methoxy-2-(methoxymethoxy)phenyl]-N-(3-pyridinyl)-N-(4-pyridinylmethyl)urea | C25H30N4O4 | 详情 | 详情 |