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【结 构 式】 
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【药物名称】842470, GW-842470, AWD-12-281 【化学名称】N-(3,5-Dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-indol-3-yl]-2-oxoacetamide 【CA登记号】247584-20-9 【 分 子 式 】C22H14Cl2FN3O3 【 分 子 量 】458.27958 |
【开发单位】elbion (Originator), GlaxoSmithKline (Licensee) 【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, Chronic Obstructive Pulmonary Diseases (COPD), Treatment of, Drugs for Allergic Rhinitis, RESPIRATORY DRUGS, Treatment of Upper Respiratory Tract Disorders, Phosphodiesterase IV Inhibitors |
合成路线1
The reaction of 5-methoxyindol (I) with 4-fluorobenzyl chloride in DMF gives 5-methoxy-1-(4-fluorobenzyl)indol (II). This compound is acylated with oxalyl chloride, yielding 5-methoxy-[1-(4-fluorobenzyl)indol-3-yl]glyoxylic acid chloride (III), which is transformed with 4-amino-3,5-dichloropyridine into the corresponding amide (IV). The reaction of (IV) with borontribromide in toluene cleaves the methoxy group, yielding AWD 12-281.
| 【1】 Hofgen, N.; Schupke, H.; Marx, D.; Gasparic, A.; Kronbach, T.; Hartenhauer, H.; Szelenyi, I.; Krone, D.; Hempel, R.; Kiss, H.; Berthold, K.; Egerland, U.; Olbrich, M.; Heer, S.; Rundfelt, C.; AWD 12-281. Drugs Fut 2002, 27, 2, 111. |
| 【2】 Höfgen, N.; Kronbach, T.; Plymeropoulos, E.; Marx, D.; Heer, S.; Szelenyi, S.; Egerland, U.; Poppe, H. (Arzneimittelwerk Dresden GmbH); New hydroxyindoles, their use as phosphodiesterase 4 inhibitors and method for producing same. CA 2270301; DE 19818964; WO 9955696 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12354 | 4-Fluorobenzyl chloride; 1-(Chloromethyl)-4-fluorobenzene | 352-11-4 | C7H6ClF | 详情 | 详情 | |
| 25135 | 3,5-dichloro-4-pyridinamine; 4-amino-3,5-dichloropyridine | 22889-78-7 | C5H4Cl2N2 | 详情 | 详情 | |
| (I) | 25902 | 1H-Indol-5-yl methyl ether; 5-Methoxy-1H-indole; 5-Methoxyindole | 1006-94-6 | C9H9NO | 详情 | 详情 |
| (II) | 51711 | 1-(4-fluorobenzyl)-1H-indol-5-yl methyl ether; 1-(4-fluorobenzyl)-5-methoxy-1H-indole | C16H14FNO | 详情 | 详情 | |
| (III) | 51712 | 2-[1-(4-fluorobenzyl)-5-methoxy-1H-indol-3-yl]-2-oxoacetyl chloride | C18H13ClFNO3 | 详情 | 详情 | |
| (IV) | 31732 | N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-methoxy-1H-indol-3-yl]-2-oxoacetamide | C23H16Cl2FN3O3 | 详情 | 详情 |