|
【结 构 式】 
|
【药物名称】Cimetidine, Tagamet 【化学名称】N''-Cyano-N-methyl-N'-[2-(5-methyl-1H-imidazol-4-ylmethylsulfanyl)ethyl]guanidine 【CA登记号】51481-61-9 【 分 子 式 】C10H16N6S 【 分 子 量 】252.34322 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Antiulcer Drugs, Esophageal Diseases, Treatment of, Gastric Antisecretory Drugs, Gastroesophageal Reflux Disease, Agents for, GASTROINTESTINAL DRUGS, Non-Ulcer Dyspepsia, Agents for, Histamine H2 Receptor Antagonists |
合成路线1
1) By refluxing N-cyano-N',S-dimethylisoithiourea (B) and 5-methyl-4-[(2-aminoethyl)thiomethyl imidazol (III) in acetonitrile. The latter is prepared by reacting cysteamine (A) and 5-methyl-4-(hydroxymethyl)imidazol (II) (from 5-methylimidazol (I) and formalin) in acetic acid, in hydrochloric acid or in hydrobromic acid. 2) By reaction of 5-methyl-4-[(2-aminoethyl)thiomethyl]imidazol (III) with cyanodithioimido carbonic (C) acid dimethyl ester to give the isothiourea (IV), followed by reaction with methylamine. 3) By refluxing 1-methyl-3-[2-[[(5-methylimidazol-4-yl)-methyl]thio]ethyl]-2-thiourea (metiamide) (V) and lead cyanamide. The first is prepared by reaction of 5-methyl-4-[(2-aminoethyl)thiomethyl]imidazol (III) with methyl isocyanate (D).
| 【1】 Durant, G.J.; et al.; Pharmacologically active guanidine compounds. DE 2211454; DE 2265369; FR 2128505; GB 1338169; US 3950333 . |
| 【2】 Erlenmeyer, H.; et al.; Helv Chim Acta 1948, 31, 32. |
| 【3】 Durant, G.J.; et al.; Certain N-cyanoguanidines. DE 2344779; FR 2199467; GB 1397436; JP 49075574; US 3876647 . |
| 【4】 Castaner, J.; Cimetidine. Drugs Fut 1976, 1, 1, 13. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (D) | 12092 | Methyl isothiocyanate; MITC; (Methylimino)(thioxo)methane | 556-61-6 | C2H3NS | 详情 | 详情 |
| (A) | 13186 | 2-Aminoethanethiol; 2-Amino-1-ethanethiol; 2-Aminoethylhydrosulfide; Cysteamine | 60-23-1 | C2H7NS | 详情 | 详情 |
| (B) | 34072 | [[(E)-(methylamino)(methylsulfanyl)methylidene]amino](nitrilo)methane | C4H7N3S | 详情 | 详情 | |
| (I) | 34070 | 5-methyl-1H-imidazole | 822-36-6 | C4H6N2 | 详情 | 详情 |
| (II) | 14216 | (5-Methyl-1H-imidazol-4-yl)methanol | 29636-87-1 | C5H8N2O | 详情 | 详情 |
| (III) | 34071 | 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]-1-ethanamine; 2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethylamine | C7H13N3S | 详情 | 详情 | |
| (IV) | 34073 | 4-[[(2-[[(cyanoimino)(methylsulfanyl)methyl]amino]ethyl)sulfanyl]methyl]-5-methyl-1H-imidazole | C10H15N5S2 | 详情 | 详情 | |
| (V) | 34074 | N-methyl-N'-(2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl]ethyl)thiourea | C9H16N4S2 | 详情 | 详情 | |
| (C) | 18174 | [[bis(methylsulfanyl)methylene]amino](nitrilo)methane | 10191-60-3 | C4H6N2S2 | 详情 | 详情 |