|
【结 构 式】 
|
【药物名称】Ibandronate sodium hydrate, Ibandronic acid monosodium salt monohydrate, Ro-200-5450, R-484, RPR-102289A, BM-21.0955 monosodium salt monohydrate, Boniva, Destara, Bonviva(former Brand Name), Bondronat 【化学名称】[1-Hydroxy-3-(N-methyl-N-pentylamino)propylidene]bisphosphonic acid monosodium salt monohydrate 【CA登记号】138926-19-9, 138844-81-2 (anhydrous), 114084-78-5 (anhydrous free acid) 【 分 子 式 】C9H24NNaO8P2 【 分 子 量 】359.23093 |
【开发单位】Chugai (Originator), Roche (Originator), GlaxoSmithKline (Codevelopment), Roche (Codevelopment) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Bone Cancer Therapy, Bone Diseases, Treatment of, Bone Resorption Inhibitors, Breast Cancer Therapy, METABOLIC DRUGS, Oncolytic Drugs, Prevention of Osteoporosis, Treatment of Hypercalcemia, Treatment of Osteoporosis, Bisphosphonates |
合成路线1
| 【1】 Baetz F,JunghansB 2006. Improved process for the preparation of sodium ibandronate, [l-hydroxy-3-(methylpentylamino) propylidene] bisphosphonic acid monosodium salt mmohydrate W0 2006045578（本专利申请人为F．Hoffmann-IA Roche AG, Switz） |
| 【2】 Grassi S,Volante A. 2005. An improved process for the preparation of alkyl- and aryl-substituted-hydroxy-l,l-ethanediphosphonic acids and salts thereof by solvent-free reaction of carboxylic acids with pbosphoxous acid and phosphorus oxychloride. W0 2005063779(本专利申请人为Lyogen Limited, Cyprus) |
| 【3】 Szabo CM, Matsumura Y, Fukrua S,et aL 2002. Inhibition of geranylgeranyl diphosphate synthase by bisphosphontes and diphosphates: a potential route to new bone antiresorption ru,d antiparasitic agents.J Med Che:m, 45 (11): 2185~2196 |
| 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) | 15764 | amylamine; 1-pentanamine; pentylamine | 110-58-7 | C5H13N | 详情 | 详情 |
| (II) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (III) | 15766 | N-pentyl-N-[(E)-benzylidene]amine; N-[(E)-benzylidene]-1-pentanamine | C12H17N | 详情 | 详情 | |
| (IV) | 15767 | N-Methylamylamine; N-methyl-N-pentylamine; N-methyl-1-pentanamine | 25419-06-1 | C6H15N | 详情 | 详情 |
合成路线2
| 【1】 Pulla Reddy M.2007. Improved process for the preparation of ibandronate sodium. W0 2007013097[本专利为Natco Pharma Ltd(IN)所有] |
| 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) | 10847 | Acrylonitrile | 107-13-1 | C3H3N | 详情 | 详情 |
| (II) | 11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 |
| (III) | 24278 | 3-(methylamino)propanenitrile | 693-05-0 | C4H8N2 | 详情 | 详情 |
| (IV) | 66461 | 3-(methyl(pentyl)amino)propanenitrile | C9H18N2 | 详情 | 详情 | |
| (V) | 15769 | 3-[methyl(pentyl)amino]propionic acid | C9H19NO2 | 详情 | 详情 |
合成路线3
Starting from N-pentylamine (I), the intermediate N-methyl-N-pentylamine (IV) is condensed with methyl methacrylate to give N-methyl-N-pentyl-beta-alanine methyl ester (V). After hydrolysis of the methyl ester (V), the bisphosphonate is produced in the common way using phosphorous oxychloride/phosphorous acid.
| 【1】 Muhlbauer, R.C.; Bauss, F.; BM-21.0955, Monosodium Salt, Monohydrate. Drugs Fut 1994, 19, 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 |
|---|---|---|---|---|---|---|
| (I) | 15764 | amylamine; 1-pentanamine; pentylamine | 110-58-7 | C5H13N | 详情 | 详情 |
| (II) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (III) | 15766 | N-pentyl-N-[(E)-benzylidene]amine; N-[(E)-benzylidene]-1-pentanamine | C12H17N | 详情 | 详情 | |
| (IV) | 15767 | N-Methylamylamine; N-methyl-N-pentylamine; N-methyl-1-pentanamine | 25419-06-1 | C6H15N | 详情 | 详情 |
| (V) | 15768 | methyl 3-[methyl(pentyl)amino]propanoate | C10H21NO2 | 详情 | 详情 | |
| (VI) | 15769 | 3-[methyl(pentyl)amino]propionic acid | C9H19NO2 | 详情 | 详情 |