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【结 构 式】 
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【药物名称】Isbogrel, A-66900, CV-4151 【化学名称】(E)-7-Phenyl-7-(3-pyridyl)-6-heptenoic acid 【CA登记号】89667-40-3 【 分 子 式 】C18H19NO2 【 分 子 量 】281.35763 |
【开发单位】Takeda (Originator), TAP (Licensee) 【药理作用】Antiplatelet Therapy, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Prostanoid TP (Thromboxane A2) Antagonists, Thromboxane Synthase Inhibitors |
合成路线1
The condensation of 6-bromohexanoic acid (I) with triphenylphosphine in refluxing acetonitrile gives the corresponding phosphonium salt (III), which is submitted to a Wittig condensation with phenyl 3-pyridyl ketone (IV) by means of NaH in DMSO, yielding a mixture of the title product and its (Z)-isomer (V). This mixture of isomers is separated by fractional crystallization or HPLC and the isomeric compound (V) is treated with refluxing aqueous 25% HBr to perform its isomerization to CV-415.
| 【1】 Kato, K.; et al.; Thromboxane synthetase inhibitors (TXSI). Design, synthesis, and evaluation of a novel series of omega-pyridilalkenoic acids. J Med Chem 1985, 28, 3, 287-294. |
| 【2】 Terao, S.; et al. (Takeda Chemical Industries, Ltd.); Substituted vinylcarboxylic acid derivative and its preparation. JP 58219162 . |
| 【3】 Castaner, J.; Serradell, M.N.; CV-4151. Drugs Fut 1986, 11, 3, 183. |
| 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) | 27765 | 6-bromohexanoic acid | 4224-70-8 | C6H11BrO2 | 详情 | 详情 |
| (III) | 18264 | (5-Carboxypentyl)triphenylphosphonium bromide; (5-carboxypentyl)(triphenyl)phosphonium bromide | 50889-29-7 | C24H26BrO2P | 详情 | 详情 |
| (IV) | 27766 | phenyl(3-pyridinyl)methanone | 5424-19-1 | C12H9NO | 详情 | 详情 |
| (V) | 27767 | (Z)-7-phenyl-7-(3-pyridinyl)-6-heptenoic acid | C18H19NO2 | 详情 | 详情 |