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【结 构 式】 
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【药物名称】 【化学名称】7-[4-[6-(2-Chlorophenyl)-1,4-dimethyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-9-ylmethyl]phenyl]-7-(3-pyridyl)-6(E/Z)-heptenoic acid ethyl ester 【CA登记号】 【 分 子 式 】C40H41ClN6O2S 【 分 子 量 】705.32877 |
【开发单位】Nikken Chemicals (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, ANTIINFECTIVE THERAPY, Antiplatelet Therapy, Asthma Therapy, Cerebrovascular Diseases, Treatment of, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, RESPIRATORY DRUGS, Stroke, Treatment of, Treatment of Septic Shock, Platelet-Activating Factor (PAF) Antagonists, Thromboxane Synthase Inhibitors |
合成路线1
The Wittig condensation of 1-[4-(tert-butyldiphenylsilyloxymethyl)phenyl]-1-(3-pyridyl)methanone (I) with phosphonium bromide (II) by means of NaH in tert-butanol gives the heptenoic ester (III), which is desilylated with TBAF in THF to yield 7-[4-(hydroxymethyl)phenyl]-7-(3-pyridyl)-6-heptenoic acid ethyl ester (IV). The reaction of (IV) with Ms-Cl and TEA affords the corresponding mesylate (V), which is finally condensed with the triazolodiazepine (VI) by means of K2CO3 and 18-crown-6 in DMF.
| 【1】 Fujita, M.; et al.; Novel agents combining platelet activating factor (PAF) receptor antagonist with thromboxane synthase inhibitor (TxSI). Bioorg Med Chem Lett 2002, 12, 5, 771. |
| 【2】 Sano, T.; Seki, T.; Fujita, M.; Inada, H. (Nikken Chemicals Co., Ltd.); Triazolo-1,4-diazepine cpds. and medicinal compsn. containing the same. EP 0995752; JP 1999071378; US 6433167; WO 9858930 . |
| 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) | 54466 | [4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl](3-pyridinyl)methanone | C29H29NO2Si | 详情 | 详情 | |
| (II) | 54467 | (6-ethoxy-6-oxohexyl)(triphenyl)phosphonium bromide | C26H30BrO2P | 详情 | 详情 | |
| (III) | 54468 | ethyl (E)-7-[4-({[tert-butyl(diphenyl)silyl]oxy}methyl)phenyl]-7-(3-pyridinyl)-6-heptenoate | C37H43NO3Si | 详情 | 详情 | |
| (IV) | 54469 | ethyl (E)-7-[4-(hydroxymethyl)phenyl]-7-(3-pyridinyl)-6-heptenoate | C21H25NO3 | 详情 | 详情 | |
| (V) | 54470 | ethyl (E)-7-(4-{[(methylsulfonyl)oxy]methyl}phenyl)-7-(3-pyridinyl)-6-heptenoate | C22H27NO5S | 详情 | 详情 | |
| (VI) | 14057 | 6-(2-Chlorophenyl)-1,4-dimethyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine | C19H18ClN5S | 详情 | 详情 |