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【结 构 式】 
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【药物名称】 【化学名称】2-[3-(4-Chlorophenyl)-2-propenyl]-5,6-bis(4-methoxyphenyl)pyridazin-3(2H)-one 【CA登记号】225666-41-1 【 分 子 式 】C27H23ClN2O3 【 分 子 量 】458.94896 |
【开发单位】Kowa (Originator) 【药理作用】Antiarthritic Drugs, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES, IL-1beta Production Inhibitors |
合成路线1
Glyoxylic acid (II), generated in situ by oxidative cleavage of tartaric acid (I) with sodium periodate, was condensed with deoxyanisoin (III) to provide the aldol adduct (IV). Cyclization of hydroxyacid (IV) with hydrazine gave rise to the hydroxy dihydropyridazinone (V), which was further dehydrated to (VI) upon treatment with p-toluenesulfonic acid in refluxing benzene. Finally, alkylation of pyridazinone (VI) with 4-chlorocinnamyl chloride (VII) in the presence of potassium carbonate furnished the title compound.
| 【1】 Matsuda, T.; et al.; Synthesis and bioactivities of novel 5,6-bis(4-methoxyphenyl)-2H-pyridazin-3-one derivatives: Inhibitors of interleukin-1 beta (IL-1beta) production. Bioorg Med Chem Lett 2001, 11, 17, 2373. |
| 【2】 Yoshizaki, H.; Habata, Y.; Kumai, N.; Kotaki, K.; Ohkuchi, M.; Ohgiya, T.; Yamazaki, Y.; Matsuda, T.; Kitamura, T.; Koshi, T.; Kyotani, Y.; Shigyo, H. (Kowa Co., Ltd.); Novel pyridazine derivs. and drugs containing the same as the active ingredient. EP 1043317; JP 1999152274; JP 2000198776; US 6348468; WO 9925697 . |
| 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) | 52118 | Uvic Acid; Tartaric acid; Dihydroxysuccinic acid; 2,3-Dihydroxybutanedioic acid | 133-37-9 | C4H6O6 | 详情 | 详情 |
| (II) | 15618 | 2-Oxoacetic acid; Glyoxylic Acid | 298-12-4 | C2H2O3 | 详情 | 详情 |
| (III) | 22991 | 1,2-bis(4-methoxyphenyl)-1-ethanone | 120-44-5 | C16H16O3 | 详情 | 详情 |
| (IV) | 52114 | 2-hydroxy-3,4-bis(4-methoxyphenyl)-4-oxobutyric acid | C18H18O6 | 详情 | 详情 | |
| (V) | 52115 | 4-hydroxy-5,6-bis(4-methoxyphenyl)-4,5-dihydro-3(2H)-pyridazinone | C18H18N2O4 | 详情 | 详情 | |
| (VI) | 52116 | 5,6-bis(4-methoxyphenyl)-3(2H)-pyridazinone | C18H16N2O3 | 详情 | 详情 | |
| (VII) | 52117 | 1-chloro-4-[(E)-3-chloro-1-propenyl]benzene | C9H8Cl2 | 详情 | 详情 |