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【结 构 式】 
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【药物名称】HP-19 【化学名称】[1R-(1alpha,3abeta,4beta,5alpha,7aalpha)]-2-[5-(5-Cyano-1-methylenepentyl)-1-[1(R),5-dimethylhexyl]-7a-methylperhydroinden-4-yl]acetic acid 【CA登记号】219579-76-7 【 分 子 式 】C27H45NO2 【 分 子 量 】415.6652 |
【开发单位】Georgia Institute of Technology (Originator), Mayo Clinic (Originator), University of Arizona (Originator) 【药理作用】Oncolytic Drugs, Inhibitors of Signal Transduction Pathways |
合成路线1
Ozonolysis of chloesteryl acetate (I) produced keto acid (II), which was converted to the B-homo-6-oxacholestenone (III) upon treatment with SOCl2. Subsequent displacement of the 3-beta-acetate group of (III) by NaN3 afforded azide (IV). Pyrolysis of (IV) over silica gel at 180 C yielded a mixture of cleavage products, from which the required nitrile (V) was isolated by column chromatography. Finally, selective hydrogenation of the conjugated double bond using Pd/C furnished the title compound.
| 【1】 Peng, H.; Xie, W.; Otterness, D.M.; et al.; Synthesis and biological activities of a novel group of steroidal derived inhibitors for human CDC25A protein phosphatase. J Med Chem 2001, 44, 5, 834. |
| 【2】 Peng, H.; Zalkow, L.H.; Abraham, R.T.; Powis, G.; Novel CDC25A phosphatase inhibitors from pyrolysis of 3-alpha-azido-B-homo-6-oxa-4-cholesten-7-one on silica gel. J Med Chem 1998, 41, 24, 4677. |
| 【3】 Peng, H.; Zalkow, L.H. (Georgia Technology Research Corp.); Seco-cholestane derivs. and methods of making the same. US 6011058 . |
| 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) | 16813 | (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 604-35-3 | C29H48O2 | 详情 | 详情 |
| (II) | 29439 | 2-[(1R,3aS,4S,5S,7aR)-5-[(1R,4S)-4-(acetoxy)-1-methyl-2-oxocyclohexyl]-1-[(1R)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-yl]acetic acid | C29H48O5 | 详情 | 详情 | |
| (III) | 29440 | (1R,3aS,3bS,8S,10aR,10bS,12aR)-1-[(1R)-1,5-dimethylhexyl]-10a,12a-dimethyl-5-oxo-2,3,3a,3b,4,5,8,9,10,10a,10b,11,12,12a-tetradecahydro-1H-indeno[4,5-d][1]benzoxepin-8-yl acetate | C29H46O4 | 详情 | 详情 | |
| (IV) | 29441 | (1R,3aS,3bS,8R,10aR,10bS,12aR)-8-azido-1-[(1R)-1,5-dimethylhexyl]-10a,12a-dimethyl-1,2,3,3a,3b,4,8,9,10,10a,10b,11,12,12a-tetradecahydro-5H-indeno[4,5-d][1]benzoxepin-5-one | C27H43N3O2 | 详情 | 详情 | |
| (V) | 29442 | 2-[(1R,3aS,4R,5S,7aR)-5-[(Z)-5-cyano-1-methylene-4-pentenyl]-1-[(1R)-1,5-dimethylhexyl]-7a-methyloctahydro-1H-inden-4-yl]acetic acid | C27H43NO2 | 详情 | 详情 |