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【结 构 式】 
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【药物名称】NU-3076 【化学名称】2,2',2'',2'''-[4,8-Bis(4-methoxybenzylamino)pyrimido[5,4-d]pyrimidine-2,6-diyl]bis(nitrilo)tetrakis(ethanol) 【CA登记号】213839-95-3 【 分 子 式 】C30H40N8O6 【 分 子 量 】608.7033 |
【开发单位】University of Newcastle upon Tyne (Originator) 【药理作用】Antineoplastic Enhancing Agents, Modulators of the Therapeutic Activity of Antineoplastic Agents, ONCOLYTIC DRUGS, Drugs Acting on Purine Nucleoside Transporters |
合成路线1
Pyrimidopyrimidine tetraone (I) was converted to the disodium salt (II), which was then treated with PCl5 in refluxing POCl3 to provide the tetrachloro pyrimidopyrimidine (III). Displacement of the more reactive 4- and 8-chlorine atoms of (III) by 4-methoxybenzylamine (IV) in THF at room temperature gave the 4,8-di(4-methoxybenzylamino) derivative (V). Finally, the remainig chlorine atoms of (V) were displaced by diethanolamine (VI) at 110 C, yielding the title compound.
| 【1】 Barlow, H.C.; et al.; Resistance-modifying agents. Part 7: 2,6-Disubstituted-4,8-dibenzylaminopyrimido[5,4-d]pyrimidines that inhibit nucleoside transport in the presence of alpha1-acid glycoprotein (AGP). Bioorg Med Chem Lett 2000, 10, 6, 585. |
| 【2】 Calvert, A.H.; Griffin, R.J.; Curtin, N.J.; Golding, B.T.; Newell, D.R. (University of Newcastle upon Tyne); Pyrimidopyrimidine cpds.. WO 9843974 . |
| 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) | 41123 | 1,5-dihydropyrimido[5,4-d]pyrimidine-2,4,6,8(3H,7H)-tetrone | 6713-54-8 | C6H4N4O4 | 详情 | 详情 |
| (II) | 41124 | disodium 2,6-dioxo-1,2,6,7-tetrahydropyrimido[5,4-d]pyrimidine-4,8-diolate | C6H2N4Na2O4 | 详情 | 详情 | |
| (III) | 36173 | 2,4,6,8-tetrachloropyrimido[5,4-d]pyrimidine | C6Cl4N4 | 详情 | 详情 | |
| (IV) | 15098 | 4-Methoxybenzylamine; (4-Methoxyphenyl)methanamine | 2393-23-9 | C8H11NO | 详情 | 详情 |
| (V) | 41125 | 2,6-dichloro-N(4),N(8)-bis(4-methoxybenzyl)pyrimido[5,4-d]pyrimidine-4,8-diamine; N-[2,6-dichloro-8-[(4-methoxybenzyl)amino]pyrimido[5,4-d]pyrimidin-4-yl]-N-(4-methoxybenzyl)amine | C22H20Cl2N6O2 | 详情 | 详情 | |
| (VI) | 24273 | 2-[(2-hydroxyethyl)amino]-1-ethanol | 111-42-2 | C4H11NO2 | 详情 | 详情 |