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【结 构 式】 
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【药物名称】 【化学名称】3,4,5-Trimethoxybenzoic acid 2,4-diaminoquinazolin-6-ylmethyl ester 【CA登记号】 【 分 子 式 】C19H20N4O5 【 分 子 量 】384.39505 |
【开发单位】Melacure Therapeutics (Originator) 【药理作用】AIDS Medicines, ANTIINFECTIVE THERAPY, Pneumocystis carinii Pneumonia, Agents for, Treatment of Opportunistic Infections, Treatment of Protozoal Diseases, Dihydrofolate Reductase (DHFR) Inhibitors |
合成路线1
Nitrile (II) was prepared by regioselective diazotization of triaminoquinazoline (I), followed by treatment with KCN and CuSO4. Conversion of nitrile (II) into aldehyde (III) was achieved by means of Ni-Al alloy in refluxing formic acid. Subsequent reduction of aldehyde (III) with NaBH4 gave alcohol (IV), which was further brominated to (V) using HBr in HOAc. Finally, displacement of the bromide of (V) with 3,4,5-trimethoxybenzoic acid (VI) provided the target trimethoxybenzoate ester.
| 【1】 Graffner-Nordberg, M.; et al.; Design, synthesis, computational prediction, and biological evaluation of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii. J Med Chem 2001, 44, 15, 2391. |
| 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) | 52638 | 2,4,6-quinazolinetriamine | 13741-90-7 | C8H9N5 | 详情 | 详情 |
| (II) | 52639 | 2,4-diamino-6-quinazolinecarbonitrile | C9H7N5 | 详情 | 详情 | |
| (III) | 52640 | 2,4-diamino-6-quinazolinecarbaldehyde | C9H8N4O | 详情 | 详情 | |
| (IV) | 52641 | (2,4-diamino-6-quinazolinyl)methanol | C9H10N4O | 详情 | 详情 | |
| (V) | 47618 | 6-(bromomethyl)-2,4-quinazolinediamine; 2-amino-6-(bromomethyl)-4-quinazolinylamine | C9H9BrN4 | 详情 | 详情 | |
| (VI) | 32225 | 3,4,5-trimethoxybenzoic acid | 118-41-2 | C10H12O5 | 详情 | 详情 |