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【结 构 式】 
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【药物名称】OC144-093, ONT-093, OC-144-093 【化学名称】N-[4-[2-[4-[3-Ethoxy-1(E)-propenyl]phenyl]-4-[4-(isopropylamino)phenyl]-1H-imidazol-5-yl]phenyl]-N-isopropylamine 【CA登记号】216227-54-2 【 分 子 式 】C32H38N4O 【 分 子 量 】494.68586 |
【开发单位】Ontogen (Originator) 【药理作用】Modulators of the Therapeutic Activity of Antineoplastic Agents, Multidrug Resistance Modulators, ONCOLYTIC DRUGS |
合成路线1
Palladium-catalyzed coupling of 4-bromobenzaldehyde (I) with methyl acrylate (II) furnished methyl 4-formylcinnamate (III). After aldehyde protection as the ethylene acetal (IV), ester group reduction using DIBAL in cold CH2Cl2 gave rise to the cinnamyl alcohol (V). O-Alkylation of (V) with ethyl iodide in the presence of NaH produced the corresponding ethyl ether (VI). The acetal protecting group of (VI) was then hydrolyzed with HCl to yield aldehyde (VII).
| 【2】 Zhang, C.; Mjalli, A.M.M. (Ontogen Corp.); Imidazole derivs. as MDR modulators. EP 0999835; US 5840721; WO 9902155 . |
| 【1】 Dixon, R.; Zhang, C.; Sarshar, S.; Mjalli, A.M.M.; Rodarte, J.C.; Moran, E.J.; Benbatoul, K.D.; Krane, S.; 2,4,5-Trisubstituted imidazoles: Novel nontoxic modulators of P-glycoprotein mediated multidrug resistance. Part 2. Bioorg Med Chem Lett 2000, 10, 23, 2603. |
| 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) | 22231 | 4-Bromobenzaldehyde | 1122-91-4 | C7H5BrO | 详情 | 详情 |
| (II) | 14156 | methyl acrylate | 96-33-3 | C4H6O2 | 详情 | 详情 |
| (III) | 46515 | methyl (E)-3-(4-formylphenyl)-2-propenoate | 7560-50-1 | C11H10O3 | 详情 | 详情 |
| (IV) | 46516 | methyl (E)-3-[4-(1,3-dioxolan-2-yl)phenyl]-2-propenoate | C13H14O4 | 详情 | 详情 | |
| (V) | 46517 | (E)-3-[4-(1,3-dioxolan-2-yl)phenyl]-2-propen-1-ol | C12H14O3 | 详情 | 详情 | |
| (VI) | 46518 | (E)-3-[4-(1,3-dioxolan-2-yl)phenyl]-2-propenyl ethyl ether; 2-[4-[(E)-3-ethoxy-1-propenyl]phenyl]-1,3-dioxolane | C14H18O3 | 详情 | 详情 | |
| (VII) | 46519 | 4-[(E)-3-ethoxy-1-propenyl]benzaldehyde | C12H14O2 | 详情 | 详情 |
合成路线2
Treatment of 4,4'-difluorobenzyl (VIII) with isopropylamine and K2CO3 in hot DMSO produced 4,4'-bis(isopropylamino)benzyl (IX). This was then condensed with the intermediate aldehyde (VII) in the presence of ammonium acetate in HOAc to produce the target triaryl imidazole.
| 【2】 Zhang, C.; Mjalli, A.M.M. (Ontogen Corp.); Imidazole derivs. as MDR modulators. EP 0999835; US 5840721; WO 9902155 . |
| 【1】 Dixon, R.; Zhang, C.; Sarshar, S.; Mjalli, A.M.M.; Rodarte, J.C.; Moran, E.J.; Benbatoul, K.D.; Krane, S.; 2,4,5-Trisubstituted imidazoles: Novel nontoxic modulators of P-glycoprotein mediated multidrug resistance. Part 2. Bioorg Med Chem Lett 2000, 10, 23, 2603. |