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【结 构 式】 
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【药物名称】NSC-651016 【化学名称】4,4'-Carbonylbis(1H-pyrrol-4,2-diyl)bis(carbonylimino)bis(1-methylpyrrol-4,2-diyl)bis(carbonylimino)bis(naphthalene-1,7-disulfonic acid disodium salt) 【CA登记号】208576-37-8 (error in CA) 【 分 子 式 】C43H32N10Na4O17S4 【 分 子 量 】1181.00649 |
【开发单位】National Cancer Institute (Originator), University of Vermont (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY, Chemokine CCR1 Antagonists, Chemokine CCR2 (MCP-1) Antagonists, Chemokine CCR5 Antagonists |
合成路线1
The reaction of 4-aminonaphthalene-1,7-disulfonic acid disodium salt (I) with 1-methyl-4-nitropyrrole-2-carbonyl chloride (II) by means of NaOAc in water gives the corresponding nitro-amide (III), which is reduced with H2 over Pd/C in water to the amino-amide (IV). The reaction of (IV) with 4-nitropyrrole-2-carbonyl chloride (V) by means of NaOH and NaOAc yields the nitro-diamide (VI), which is reduced with H2 over Pd/C as before affording the amino-diamide (VII). Finally, this compound is dimerized by reaction with phosgene and KOAc in dioxane/water.
| 【1】 Bigelow, J.; Oppenheim, J.J.; Rice, W.G.; Buckheit, R.W.; Covey, J.M.; Howard, O.M.Z.; Clanton, D.J.; McCormack, J.J.; Hollisgshead, M.G.; Turpin, J.A.; Inhibition of in vitro and in vivo HIV replication by a distamycin analogue that interferes with chemokine receptor function: A candidate for chemotherapeutic and microbicidal application. J Med Chem 1998, 41, 13, 2184. |
| 【2】 Mongelli, N.; Biasoli, G.; Paio, A.; Grandi, M.; Ciomei, M. (Pharmacia Corp.); New ureido derivs. of poly-4-amino-2-carboxy-1-methyl cpds.. EP 0462258; JP 1992504426; US 5260329; US 5420296; WO 9110649 . |
| 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) | 27851 | disodium 4-amino-1,7-naphthalenedisulfonate | C10H7NNa2O6S2 | 详情 | 详情 | |
| (II) | 27852 | 1-methyl-4-nitro-1H-pyrrole-2-carbonyl chloride | C6H5ClN2O3 | 详情 | 详情 | |
| (III) | 27853 | disodium 4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1,7-naphthalenedisulfonate | C16H11N3Na2O9S2 | 详情 | 详情 | |
| (IV) | 27854 | 4-nitro-1H-pyrrole-2-carbonyl chloride | C5H3ClN2O3 | 详情 | 详情 | |
| (V) | 27855 | disodium 4-[[(1-methyl-4-[[(4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1,7-naphthalenedisulfonate | C21H15N5Na2O10S2 | 详情 | 详情 | |
| (VI) | 27856 | disodium 4-[[(4-[[(4-amino-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1,7-naphthalenedisulfonate | C21H17N5Na2O8S2 | 详情 | 详情 | |
| (VII) | 27857 | 4-(1,1,2,2-tetrafluoroethoxy)aniline | 713-62-2 | C8H7F4NO | 详情 | 详情 |