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【结 构 式】 
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【药物名称】MR-20492 【化学名称】(Z)-6-(4-Chlorophenyl)-7-(pyridin-4-ylmethylene)-5,6,7,8- tetrahydroindolizin-8-one 【CA登记号】 【 分 子 式 】C20H15ClN2O 【 分 子 量 】334.80835 |
【开发单位】Univ. Caen, Caen (FR); CNRS 【药理作用】ONCOLYTIC DRUGS, HORMONAL AGENTS |
合成路线1
Title compound was prepared by condensation of tetrahydroindolizinone (I) with pyridine-4-carboxyaldehyde (II) under phase transfer conditions using NaOH and tetrabutyl hydrogensulfate in a mixture of H2O and CH2Cl2.
| 【1】 Sonnet, P.; Guillon, J.; Enguehard, C.; Dallemagne, P.; Bureau, R.; Rault, S.; Auvray, P.; Moslemi, S.; Sourdiane, P.; Galopin, S.; Seralini, G.E.; Design and synthesis of a new type of non steroidal human aromatase inhibitors. Bioorg Med Chem Lett 1998, 8, 9, 1041. |
| 【2】 Sonnet, P.; Dallemagne, P.; Guillon, J.; et al.; New aromatase inhibitors. Synthesis and biological activity of aryl-substituted pyrrolizine and indolizine derivatives. Bioorg Med Chem 2000, 8, 5, 945. |
合成路线2
The cyclization of the amino group of 4-amino-3-(4-chlorophenyl)butyric acid (I) with 2,5-dimethoxytetrahydrofuran (II) by means of AcOH in THF gives the corresponding pyrrole (III), which is cyclized by means of TEA, ClCOOEt, pyrrolidine and POCl3 in toluene yielding the pyrrolopyridone (IV). Finally, this compound is condensed with pyridine-4-carbaldehyde (V) by means of tetrabutylammonium bisulfate and NaOH in water.
| 【1】 Moslemi, S.; Dallemagne, P.; Enguehard, C.; Sonnet, P.; Séralini, G.-E.; Bureau, R.; Auvray, P.; Sourdaine, P.; Guillon, J.; Rault, S.; MR 20492 and MR 20494: Two indolizinone derivatives that strongly inhibit human aromatase. J Steroid Biochem Mol Biol 1999, 70, 1-3, 59. |
| 【2】 Sonnet, P.; Dallemagne, P.; Guillon, J.; et al.; New aromatase inhibitors. Synthesis and biological activity of aryl-substituted pyrrolizine and indolizine derivatives. Bioorg Med Chem 2000, 8, 5, 945. |
| 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) | 36490 | 4-amino-3-(4-chlorophenyl)butyric acid | 1134-47-0 | C10H12ClNO2 | 详情 | 详情 |
| (II) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
| (III) | 36491 | 3-(4-chlorophenyl)-4-(1H-pyrrol-1-yl)butyric acid | C14H14ClNO2 | 详情 | 详情 | |
| (IV) | 18742 | 6-(4-chlorophenyl)-6,7-dihydro-8(5H)-indolizinone | C14H12ClNO | 详情 | 详情 | |
| (V) | 17203 | 4-Pyridinecarboxaldehyde; isonicotinaldehyde | 872-85-5 | C6H5NO | 详情 | 详情 |