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【结 构 式】 
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【药物名称】Seratrodast, ABT-001, A-73001, Abbott-73001, AA-2414, Bronica 【化学名称】(±)-7-Phenyl-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)heptanoic acid 【CA登记号】112665-43-7, 103187-09-3 (R-isomer), 103196-89-0 (S-isomer), 103186-19-2 (undefined stereoch.) 【 分 子 式 】C22H26O4 【 分 子 量 】354.45012 |
【开发单位】Takeda (Originator), Abbott (Licensee), TAP (Licensee), Grelan (Comarketer) 【药理作用】Asthma Therapy, Chronic Obstructive Pulmonary Diseases (COPD), Treatment of, RESPIRATORY DRUGS, Prostanoid TP (Thromboxane A2) Antagonists |
合成路线1
The reaction of pimelic acid monoester (I) with refluxing SOCl2 gives the corresponding acid chloride (II), which by a Friedel-Craft's condensation with benzene (AlCl3 as catalyst) is converted into 6-benzoylhexanoic acid ethyl ester (III). The reduction of (III) with NaBH4 in methanol affords 7-hydroxy-7-phenylheptanoic acid ethyl ester (IV), which is hydrolyzed with NaOH in hot THF - water to yield the corresponding free acid (V). Finally, this compound is condensed with trimethylhydroquinone (VI) by means of boron trifluoride ethearate in hot toluene.
| 【1】 Terao, S.; Maki, Y. (Takeda Chemical Industries, Ltd.); Quinone amides, their production and use. EP 0232089; JP 1987246545 . |
| 【2】 Terao, S.; Maki, Y. (Takeda Chemical Industries, Ltd.); Quinone derivs., their production and use. AU 8545615; EP 0171251; ES 8704870; JP 1986044840; JP 1991072444; JP 1991081248; JP 1991086841; US 5180742; WO 8600887; WO 8604058 . |
| 【3】 Shiraishi, M.; Kato, K.; Terao, S.; Ashida, Y.; Terashita, Z.-I.; Kito, G.; Quinones. 4. Novel eicosanoid antagonists: Synthesis and pharmacological evaluation. J Med Chem 1989, 32, 9, 2214-21. |
| 【4】 Terao, S.; Quinone derivatives: Synthesis and structure-activity relations of a novel class of eicosanoid antagonists, AA-2414 and its analogs. Advances in Prostaglandin, Thromboxane and Leukotriene Research 1989, 19, 651-654. |
| 【5】 Prous, J.; Castaner, J.; AA-2414. Drugs Fut 1990, 15, 8, 783. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 13364 | Benzene | 71-43-2 | C6H6 | 详情 | 详情 |
| (I) | 31145 | 7-ethoxy-7-oxoheptanoic acid | 33018-91-6 | C9H16O4 | 详情 | 详情 |
| (II) | 31146 | ethyl 7-chloro-7-oxoheptanoate | 14794-32-2 | C9H15ClO3 | 详情 | 详情 |
| (III) | 31147 | ethyl 7-oxo-7-phenylheptanoate | C15H20O3 | 详情 | 详情 | |
| (IV) | 31148 | ethyl 7-hydroxy-7-phenylheptanoate | C15H22O3 | 详情 | 详情 | |
| (V) | 31149 | 7-hydroxy-7-phenylheptanoic acid | C13H18O3 | 详情 | 详情 | |
| (VI) | 26357 | 2,3,5-trimethyl-1,4-benzenediol | 700-13-0 | C9H12O2 | 详情 | 详情 |