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【结 构 式】 
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【药物名称】ADN-311 【化学名称】2-[1-(3,4-Dichlorobenzyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-3-yl]acetic acid 【CA登记号】136148-02-2 【 分 子 式 】C17H12Cl2N2O4 【 分 子 量 】379.20219 |
【开发单位】Kyorin (Originator) 【药理作用】ENDOCRINE DRUGS, Symptomatic Antidiabetic Agents, Treatment of Diabetic Complications, Aldose Reductase Inhibitors |
合成路线1
The reaction of isatoic anhydride (I) with glycine ethyl ester (II) gives N-(2-aminobenzoyl)glycine ethyl ester (III), which is cyclized with carbonyldiimidazole (CDI) to yield 2-(2,4-dioxo-1,2,3,4-tetrahydroquinazolin-3-yl)acetic acid ethyl ester (IV). The alkylation of (IV) with 3,4-dichlorobenzyl bromide (V) affords 2-[1-(3,4-dichlorobenzyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-3-yl]acetic acid ethyl ester (VI), which is finally hydrolyzed in basic medium.
| 【1】 Itoh, Y.; Hashimoto, M.; Ao, S.; Notsu, Y.; Novel aldose reductase inhibitors: Synthesis and structure-activity studies of (3-benzyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-1-yl)acetic acids. Drugs Fut 1992, 17, 1, 31. |
| 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) | 29797 | 2H-3,1-benzoxazine-2,4(1H)-dione；Isatoic anhydride;4H-3,1-Benzoxazine-2,4(1H)-dione；1,2-Dihydro-4H-3,1-benzoxazine-2,4-dione;1H-benzo[d][1,3]oxazine-2,4-dione | 118-48-9 | C8H5NO3 | 详情 | 详情 |
| (II) | 10309 | ethyl 2-aminoacetate; Glycine ethyl ester | 459-73-4 | C4H9NO2 | 详情 | 详情 |
| (III) | 42909 | ethyl 2-[(2-aminobenzoyl)amino]acetate | C11H14N2O3 | 详情 | 详情 | |
| (IV) | 42910 | ethyl 2-[2,4-dioxo-1,4-dihydro-3(2H)-quinazolinyl]acetate | C12H12N2O4 | 详情 | 详情 | |
| (V) | 42911 | 4-(bromomethyl)-1,2-dichlorobenzene | 18880-04-1 | C7H5BrCl2 | 详情 | 详情 |
| (VI) | 42912 | ethyl 2-[1-(3,4-dichlorobenzyl)-2,4-dioxo-1,4-dihydro-3(2H)-quinazolinyl]acetate | C19H16Cl2N2O4 | 详情 | 详情 |