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【结 构 式】 
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【药物名称】MnTE-2-PyP5+, AEOL-10113 【化学名称】(SP-4-1)-[[2,2',2'',2'''-(21H,23H-Porphine-5,10,15,20-tetrayl-kappaN21,kappaN22,kappaN23,kappaN24)tetrakis[1-ethylpyridiniumato]](2-)]manganese(5+) 【CA登记号】223723-79-3, 219818-60-7 (chloride), 223723-80-6 (hexafluorophosphate salt) 【 分 子 式 】C48H44MnN8 【 分 子 量 】787.87748 |
【开发单位】Duke University (Originator), Incara (Licensee) 【药理作用】Antidiabetic Drugs, Cerebrovascular Diseases, Treatment of, ENDOCRINE DRUGS, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, ONCOLYTIC DRUGS, Preventive Agents, Radiation Therapy, Radioprotectants, Radiosensitizers, Stroke, Treatment of, Type 1 Diabetes Mellitus, Agents for, Antioxidants, Metalloporphyrins, Superoxide Dismutases |
合成路线1
Tetrakis-(2-pyridyl)porphyrin (III) was prepared by condensation between pyridine-2-carboxaldehyde (I) and pyrrole (II) in refluxing propionic acid. Metallation of porphyrin (III) was performed with MnCl2, which spontaneously underwent oxidation, yielding the Mn3+ complex (IV). Subsequent N-alkylation of the pyridine rings with ethyl iodide produced the corresponding pyridinium iodide salt, which was transformed to the analogous chloride by treatment with tetrabutylammonium chloride (1). In an alternative procedure, initial quaternization of the pyridine rings of porphyrin (III) with ethyl p-toluenesulfonate afforded (V), which was further metallated with MnCl2 to give the title compound.
| 【2】 Kachadourian, R.; et al.; Synthesis and superoxide dismuting activities of partially (1-4) beta-chlorinated derivatives of manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl)porphyrin. Inorg Chem 1999, 38, 2, 391. |
| 【3】 Bloodsworth, A.; et al.; Manganese-porphyrin reactions with lipid and lipoproteins. Free Radical Biol Med 2000, 28, 7, 1017. |
| 【4】 Batinic-Haberle, I.; Fridovich, I. (Duke University); Substd. porphyrins. EP 1045851; JP 2001521939; WO 9923097 . |
| 【1】 Batinié-Haberle, I.; et al.; Relationships among redox potentials, proton dissociation constants of pyrrolic nitrogens, and in vivo and in vitro superoxide dismutating activities of magnase(III) and iron(III) water-soluble porphyrins. Inorg Chem 1999, 38, 18, 4011. |
| 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) | 25173 | 2-pyridinecarbaldehyde | 1121-60-4 | C6H5NO | 详情 | 详情 |
| (II) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (III) | 51699 | 2,7,12,17-tetra(2-pyridinyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1(3,6).1(8,11).1(13,16)]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaene | C40H26N8 | 详情 | 详情 | |
| (IV) | 51700 | C40H24MnN8 | 详情 | 详情 | ||
| (V) | 51701 | 1-ethyl-2-[7,12,17-tris(1-ethyl-2-pyridiniumyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1(3,6).1(8,11).1(13,16)]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaen-2-yl]pyridinium | C48H46N8 | 详情 | 详情 |